bluuebunny/crossref_metadata_2025_split huggingface dataset:
Description and crystal structure of bobkingite, a new mineral from New Cliffe Hill Quarry, Stanton-under-Bardon, Leicestershire, UK
Authors: Hawthorne F. C. , Cooper M. A. , Grice J. D. , Roberts A. C. , Hubbard N. 
Published: July 2002

AbstractBobkingite, ideally is a new mineral from the New Cliffe Hill Quarry, Stantonunder-Bardon, Leicestershire, England. It occurs as very thin (⩽5 µm) transparent plates up to 0.2 mm across, perched on a compact fibrous crust of malachite and crystalline azurite attached to massive cuprite. Crystals are tabular on {001} with dominant {001} and minor {100} and {110}. Bobkingite is a soft pale blue colour with a pale-blue streak, vitreous lustre and no observable fluorescence under ultraviolet light. It has perfect {001} and fair {100} cleavages, no observable parting, conchoidal fracture, and is brittle. Its Mohs' hardness is 3 and the calculated density is 3.254 g/cm3. Bobkingite is biaxial negative with α = 1.724(2), β = 1.745(2), γ = 1.750(2), 2Vγmeas = 33(6)°, 2Vcalc = 52°, pleochroism distinct, X = very pale blue, Z = pale greenish blue, X^a = 22° (in β obtuse), Y = c, Z = b. Bobkingite is monoclinic, space group C2/m, unit-cell parameters (refined from powder data): a = 10.301(8), b = 6.758(3), c = 8.835(7)Å, β = 111.53(6)°, V = 572.1(7)Å3, Z = 2. The seven strongest lines in the X-ray powder-diffraction pattern are [d (Å), I, (hkl)]: 8.199, 100, (001); 5.502, 100, (110); 5.029, 40, (01); 2.883, 80, (310); 2.693, 40, (13); 2.263, 40, (113), (03); 2.188, 50, (23). Chemical analysis by electron microprobe and crystal-structure solution and refinement gave CuO 70.46, Cl 12.71, H2O 19.19, O≡Cl –2.87, sum 99.49 wt.%, where the amount of H2O was determined by crystal-structure analysis. The resulting empirical formula on the basis of 12 anions (including 8 (OH) and 2H2O) is Cu4.99Cl2.02O10H12. The crystal structure was solved by direct methods and refined to an R index of 2.6% for 638 observed reflections measured with X-rays on a single crystal. Three distinct (Cuϕ6) (ϕ = unspecified anion) octahedra share edges to form a framework that is related to the structures of paratacamite and the Cu2(OH)3Cl polymorphs, atacamite and clinoatacamite. The mineral is named for Robert King, formerly of the Department of Geology, Leicester University, prominent mineral collector and founding member of the Russell Society. The mineral and its name have been approved by the Commission on New Minerals and Mineral Names of the International Mineralogical Association.
Barysilite from Garpenberg Norra, Dalarna, Sweden: occurrence and crystal structure refinement
Authors: Kolitsch U. , Holtstam D. 
Published: July 2002

AbstractA new occurrence of barysilite, Pb8Mn(Si2O7)3, at the polymetallic Garpenberg Norra Zn-Pb deposit, Hedemora, Dalarna, Sweden, is described. The mineral, which forms colourless, transparent grains, is characterized by X-ray diffraction and electron-microprobe analyses. The assemblage includes tephroite, zincian jacobsite, manganoan diopside and others. The crystal structure of a barysilite crystal from Garpenberg Norra was redetermined using single-crystal X-ray diffraction data (Mo-Kα, CCD area detector) and has been refined in space groupRcwitha= 9.804(1),c= 38.416(8)Å,V= 3197.8(8)Å3, toR1 = 2.32% for 1025 ‘observed’ reflections withFo>4σ(Fo). A previous, low-precision structure determination (Lajzérowicz, 1965;R= 20%) is confirmed but improved considerably. The structure contains one distorted MnO6polyhedron with six equivalent Mn–O bonds (2.224 Å), one Si2O7disilicate unit with an Si–O–Si angle of 120.9°, and two non-equivalent Pb sites. The Pb1 site has a highly irregular, one-sided coordination with six O ligands, indicating a stereoactive 6s2lone-electron pair on the Pb2+ion, whereas the [6+3]-coordinated Pb2 site is fairly regular, with Pb–O distances of 2.540 (3×), 2.674 (3×) and 3.098 (3×) Å. The Pb2 site contains ~10% of Ca (+Ba) replacing Pb, corresponding to the structural formula Pb16(Pb,Ca)22Mn(Si2O7)3. This is the first direct proof that not only theMsite in barysilite-type Pb8M(Si2O7)3compounds can be replaced by divalent cations.
Expansion of cytolytic CD8+ natural killer T cells with limited capacity for graft-versus-host disease induction due to interferon γ production
Authors: Baker Jeanette , Verneris Michael R. , Ito Maki , Shizuru Judith A. , Negrin Robert S. 
Published: July 2002

AbstractT cells with natural killer cell phenotype and function (NKT cells) have been described in both human and murine tissues. In this study, culture conditions were developed that resulted in the expansion of CD8+ NKT cells from bone marrow, thymus, and spleen by the timed addition of interferon-γ (IFN-γ), interleukin 2 (IL-2), and anti-CD3 monoclonal antibody. After 14 to 21 days in culture, dramatic expansion of CD3+, CD8+, αβT-cell receptor+ T cells resulted with approximately 20% to 50% of the cells also expressing the NK markers NK1.1 and DX5. The CD8+ NKT cells demonstrated lytic activity against several tumor target cells with more than 90% lysis by day 14 to day 21 of culture. Cytotoxicity was observed against both syngeneic and allogeneic tumor cell targets with the greatest lytic activity by the cells expressing either NK1.1 or DX5. The expanded CD8+ NKT cells produce TH1-type cytokines with high levels of IFN-γ and tumor necrosis factor α. Expansion of the CD8+ NKT cells was independent of CD1d. Ly49 molecules were expressed on only a minority of cells. A single injection of expanded CD8+ NKT cells was capable of protecting syngeneic animals from an otherwise lethal dose of Bcl1 leukemia cells. Expanded CD8+ NKT cells produced far less graft-versus-host disease (GVHD) than splenocytes across major histocompatibility barriers, even when 10 times the number of CD8+ NKT cells as compared to splenocytes were injected. This reduction in GVHD was related to IFN-γ production since cells expanded from IFN-γ knock-out animals caused acute lethal GVHD, whereas cells expanded from animals defective in fas ligand, fas, IL-2, and perforin did not. These data indicate that CD8+ NKT cells expanded in this fashion could be useful for preserving graft-versus-leukemia activity without causing GVHD.
Hypoxia induces lytic replication of Kaposi sarcoma–associated herpesvirus
Authors: Davis David A. , Rinderknecht Andrea S. , Zoeteweij J. Paul , Aoki Yoshiyasu , Read-Connole Elizabeth L. , Tosato Giovanna , Blauvelt Andrew , Yarchoan Robert 
Published: July 2002

AbstractThere is substantial evidence that Kaposi sarcoma–associated herpesvirus (KSHV) plays an important role in the pathogenesis of all forms of Kaposi sarcoma (KS). It has been noted that KS commonly occurs in locations, such as the feet, where tissue may be poorly oxygenated. On the basis of this observation, the potential role of hypoxia in the reactivation of KSHV replication was explored by studying 2 KSHV-infected primary effusion lymphoma B-cell lines (BC-3 and BCBL-1) latently infected with KSHV. Acute and chronic exposure of these cells to hypoxia (1% O2) induced KSHV lytic replication, as indicated by an increase in intracellular lytic protein expression and detection of virus in cell supernatants by Western immunoblotting. In addition, hypoxia increased the levels of secreted viral interleukin-6. Moreover, hypoxia enhanced the lytic replication initiated by the viral inducer 12-O-tetradecanoylphorbol-13-acetate. Desferoxamine and cobalt chloride, 2 compounds that increase the intracellular levels of hypoxia-inducible factor 1, were also able to induce KSHV lytic replication. These studies suggest that hypoxia is an inducer of KSHV replication. This process may play an important role in the pathogenesis of KS.
Chronic inborn erythrocytosis leads to cardiac dysfunction and premature death in mice overexpressing erythropoietin
Authors: Wagner Klaus F. , Katschinski Dörthe M. , Hasegawa Jo , Schumacher Dunja , Meller Birgit , Gembruch Ulrich , Schramm Uda , Jelkmann Wolfgang , Gassmann Max , Fandrey Joachim 
Published: July 2002

Abstract
The most common cause of an increase of the hematocrit is secondary to elevated erythropoietin levels. Erythrocytosis is assumed to cause higher blood viscosity that could put the cardiovascular system at hemodynamic and rheological risks. Secondary erythrocytosis results from tissue hypoxia, and one can hardly define what cardiovascular consequences are caused by chronic erythrocytosis or hypoxia. Herein, a novel transgenic (tg) mouse line is characterized that is erythrocytotic because of chronic overexpression of the human erythropoietin gene. These mice grow up well, reaching a hematocrit of about 0.80 in adulthood. Blood volume of adult tg mice was markedly increased by 75%. Unexpectedly, blood pressure was not elevated and cardiac output was not decreased. Still, the adult tg mice showed features of cardiac dysfunction with increased heart weight. In vivo, high-frequency echocardiography revealed marked ventricular dilatation that was confirmed by histologic examination. Furthermore, by transmission electron microscopy, a prominent intracellular edema of the cardiomyocytes was seen. Exercise performance of the tg mice was dramatically reduced, unmasking the severity of their compromised cardiovascular function. In addition, life expectancy of the tg mice was significantly reduced to 7.4 months. Our findings suggest that severe erythrocytosis per se results in cardiac dysfunction and markedly reduced life span.
Apolipoprotein A-I inhibits the production of interleukin-1β and tumor necrosis factor-α by blocking contact-mediated activation of monocytes by T lymphocytes
Authors: Hyka Nevila , Dayer Jean-Michel , Modoux Christine , Kohno Tadahiko , Edwards Carl K. , Roux-Lombard Pascale , Burger Danielle 
Published: July 2002

AbstractTumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), essential components in the pathogenesis of immunoinflammatory diseases, are strongly induced in monocytes by direct contact with stimulated T lymphocytes. This study demonstrates that adult human serum (HS) but not fetal calf or cord blood serum displays inhibitory activity toward the contact-mediated activation of monocytes by stimulated T cells, decreasing the production of both TNF-α and IL-1β. Fractionation of HS and N-terminal microsequencing as well as electroelution of material subjected to preparative electrophoresis revealed that apolipoprotein A-I (apo A-I), a “negative” acute-phase protein, was the inhibitory factor. Functional assays and flow cytometry analyses show that high-density lipoprotein (HDL)-associated apo A-I inhibits contact-mediated activation of monocytes by binding to stimulated T cells, thus inhibiting TNF-α and IL-1β production at both protein and messenger RNA levels. Furthermore, apo A-I inhibits monocyte inflammatory functions in peripheral blood mononuclear cells activated by either specific antigens or lectins without affecting cell proliferation. These results demonstrate a new anti-inflammatory activity of HDL-associated apo A-I that might have modulating functions in nonseptic conditions. Therefore, because HDL has been shown to bind and neutralize lipopolysaccharide, HDL appears to play an important part in modulating both acute and chronic inflammation. The novel anti-inflammatory function of apo A-I reported here might lead to new therapeutic approaches in inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and atherosclerosis.
RELT, a new member of the tumor necrosis factor receptor superfamily, is selectively expressed in hematopoietic tissues and activates transcription factor NF-κB
Authors: Sica Gabriel L. , Zhu Gefeng , Tamada Koji , Liu Ding , Ni Jian , Chen Lieping 
Published: July 2002

AbstractThe members of tumor necrosis factor receptor (TNFR) superfamily have been designated as the “guardians of the immune system” due to their roles in immune cell proliferation, differentiation, activation, and death (apoptosis). This study reports the cloning of a new member of the TNFR superfamily, RELT (ReceptorExpressed in Lymphoid Tissues). RELT is a type I transmembrane glycoprotein with a cysteine-rich extracellular domain, possessing significant homology to other members of the TNFR superfamily, especially TNFRSF19, DR3, OX40, and LTβ receptor. The messenger RNA of RELT is especially abundant in hematologic tissues such as spleen, lymph node, and peripheral blood leukocytes as well as in leukemias and lymphomas. RELT is able to activate the NF-κB pathway and selectively binds tumor necrosis factor receptor-associated factor 1. Although the soluble form of RELT fusion protein does not inhibit the one-way mixed lymphocyte reaction, immobilized RELT is capable of costimulating T-cell proliferation in the presence of CD3 signaling. These results define a new member of the TNFR superfamily that may be a potential regulator of immune responses.
A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations
Authors: Levis Mark , Tse Kam-Fai , Smith B. Douglas , Garrett Elizabeth , Small Donald 
Published: July 2002

Abstract
Internal tandem duplication (ITD) mutations of the receptor tyrosine kinase FLT3 have been found in 20% to 30% of patients with acute myeloid leukemia (AML). These mutations constitutively activate the receptor and appear to be associated with a poor prognosis. Recent evidence that this constitutive activation is leukemogenic renders this receptor a potential target for specific therapy. In this study, dose-response cytotoxic assays were performed with AG1295, a tyrosine kinase inhibitor active against FLT3, on primary blasts from patients with AML. For each patient sample, the degree of cytotoxicity induced by AG1295 was compared to the response to cytosine arabinoside (Ara C) and correlated with the presence or absence of a FLT3/ITD mutation. AG1295 was specifically cytotoxic to AML blasts harboring FLT3/ITD mutations. The results suggest that these mutations contribute to the leukemic process and that the FLT3 receptor represents a therapeutic target in AML.
Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor
Authors: Monneret Guillaume , Gravel Sylvie , Diamond Michael , Rokach Joshua , Powell William S. 
Published: July 2002

AbstractProstaglandin D2 (PGD2) is released following exposure of asthmatics to allergen and acts via the adenylyl cyclase–coupled receptor for PGD2 (DP receptor). In this study, it is reported that human eosinophils possess this receptor, which would be expected to inhibit their activation. In contrast, it was found that prostaglandin D2 is a potent stimulator of eosinophil chemotaxis, actin polymerization, CD11b expression, and L-selectin shedding. These responses are specific for eosinophils, as neutrophils display little or no response to prostaglandin D2. They were not due to interaction with receptors for other prostanoids, as prostaglandins E2 and F2α, U46619 (a thromboxane A2 analogue), and carbaprostacyclin (a prostacyclin analogue) displayed little or no activity. Furthermore, they were not shared by the selective DP receptor agonist BW245C and were not prevented by the selective DP receptor antagonist BWA868C, indicating that they were not mediated by DP receptors. In contrast, the prostaglandin D2 metabolite 13,14-dihydro-15-oxoprostaglandin D2 induced eosinophil activation but did not stimulate DP receptor–mediated adenosine 3′,5′–cyclic monophosphate (cAMP) formation. These results indicate that in addition to the classic inhibitory DP1 receptor, eosinophils possess a second, novel DP2 receptor that is associated with PGD2-induced cell activation. These 2 receptors appear to interact to regulate eosinophil responses to PGD2, as blockade of DP1 receptor–mediated cAMP production by BWA868C resulted in enhanced DP2receptor–mediated stimulation of CD11b expression. The balance between DP1 and DP2 receptors could determine the degree to which prostaglandin D2 can activate eosinophils and may play a role in eosinophil recruitment in asthma.
Forced expression of the Ikaros 6 isoform in human placental blood CD34+ cells impairs their ability to differentiate toward the B-lymphoid lineage
Authors: Tonnelle Cécile , Bardin Florence , Maroc Christine , Imbert Anne-Marie , Campa Fanny , Dalloul Ali , Schmitt Christian , Chabannon Christian 
Published: July 2002

AbstractStudies in mice suggest that the Ikaros (Ik) gene encodes several isoforms and is a critical regulator of hematolymphoid differentiation. Little is known on the role of Ikaros in human stem cell differentiation. Herein, the biological consequences of the forced expression of Ikaros 6 (Ik6) in human placental blood CD34+ progenitors are evaluated. Ik6 is one of the isoforms produced from the Ikaros premessenger RNA by alternative splicing and is thought to behave as a dominant negative isoform of the gene product because it lacks the DNA binding domain present in transcriptionally active isoforms. The results demonstrate that human cord blood CD34+ cells that express high levels of Ik6 as a result of retrovirally mediated gene transfer have a reduced capacity to produce lymphoid B cells in 2 independent assays: (1) in vitro reinitiation of human hematopoiesis during coculture with the MS-5 murine stromal cell line and (2) xenotransplantation in nonobese diabetic–severe combined immunodeficient mice. These results suggest that Ikaros plays an important role in stem cell commitment in humans and that the balance between the different isoforms is a key element of this regulatory system; they support the hypothesis that posttranscriptional events can participate in the control of human hematopoietic differentiation.
A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies
Authors: Buijs Arjan , Poddighe Pino , van Wijk Richard , van Solinge Wouter , Borst Eric , Verdonck Leo , Hagenbeek Anton , Pearson Peter , Lokhorst Henk 
Published: July 2002

Abstract
Hereditary mutations associated with hematologic malignancies are rare. Heterozygous mutations affecting the hematopoietic transcription factor CBFA2 (also AML1/RUNX1) were recently reported to be associated with familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML, MIM 601399). A new 3-generation family with FPD/AML with a novel CBFA2 mutation is described. In this family, AML was diagnosed in a second-generation male. After allogeneic stem cell transplantation from his human leukocyte antigen–identical sister, a donor-derived, genetically identical leukemia developed in the recipient and the donor. Sequencing analysis identified a G-to-T transition within the CBFA2 gene, which involves codon 198, encoding a conserved aspartic acid within the DNA- binding Runt domain. Three of 5 siblings affected with the FPD/AML trait harbored the mutation in a heterozygous form. This experience underscores the necessity of performing mutation analysis of the CBFA2 gene before sibling allogeneic transplantation in families with FPD/AML.
Breast Cancer Screening in Women Previously Treated for Hodgkin’s Disease: A Prospective Cohort Study
Authors: Diller Lisa , Nancarrow Cheryl Medeiros , Shaffer Kitt , Matulonis Ursula , Mauch Peter , Neuberg Donna , Tarbell Nancy J. , Litman Heather , Garber Judy 
Published: July 2002

PURPOSE: Young women who are exposed to chest irradiation for Hodgkin’s disease (HD) are at increased risk of breast cancer; this study investigated patient awareness of breast cancer risk and patient screening behavior and assessed the utility of mammographic screening in HD survivors. PATIENTS AND METHODS: This is a prospective cohort study of 90 female long-term survivors of HD who had been treated ≥ 8 years previously with mantle irradiation (current age, 24 to 51 years). Participants completed surveys of their perceptions of breast cancer risk and screening behaviors and received written recommendations for breast examinations and mammography. Annual follow-up was conducted through medical records, telephone, and/or mailed questionnaires. RESULTS: At baseline, women were often unaware of their increased risk of breast cancer; 40% (35 of 87) reported themselves to be at equal or lower risk than women of the same age. Only 47% (41 of 87) reported having had a mammogram in the previous 24 months. Women who had received information from an oncologist were more likely to assess correctly their risk than women who received information from other sources (P < .001). Ten women developed 12 breast cancers (ductal carcinoma-in-situ [n = 2], invasive ductal carcinoma [n = 10]) during the study; two were diagnosed at study entry, and 10 during follow-up (median, 3.1 years). All cancers were evident on mammogram, and eight of 10 invasive cancers were node negative. CONCLUSION: Practitioners who care for women after HD therapy need to educate patients regarding their risks and begin early screening. Screening by mammography can detect small, node-negative breast cancers in these patients.
ZD1839, a Selective Oral Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor, Is Well Tolerated and Active in Patients With Solid, Malignant Tumors: Results of a Phase I Trial
Authors: Ranson Malcolm , Hammond Lisa A. , Ferry David , Kris Mark , Tullo Andrew , Murray Philip I. , Miller Vince , Averbuch Steve , Ochs Judy , Morris Charles , Feyereislova Andrea , Swaisland Helen , Rowinsky Eric K. 
Published: July 2002

PURPOSE: To investigate the tolerability, pharmacokinetics, and antitumor activity of the oral, selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 in patients with solid malignant tumors. PATIENTS AND METHODS: This was an open, phase I, escalating multiple-dose tolerability and pharmacokinetic trial. ZD1839 was administered once daily for 14 consecutive days followed by 14 days off treatment. Dose escalation started at 50 mg/d and continued to 925 mg or until consistent dose-limiting toxicity (DLT) was observed. RESULTS: Sixty-four patients were entered at eight dose levels. The most frequent dose-related grade 1 and 2 adverse events were an acne-like (or folliculitis) rash, nausea, and diarrhea. Three of nine patients treated at 700 mg/d developed DLT (reversible grade 3 diarrhea); grade 3 and 4 events were uncommon. Exposure to ZD1839 was dose proportional, and the mean terminal half-life was 48 hours (range, 37 to 65). Four of 16 patients with non–small-cell lung cancer (NSCLC) had objective partial responses observed from ZD1839 300 to 700 mg/d. Overall, 16 patients remained on study for ≥ 3 months, with seven of these patients (five with NSCLC, including three of the patients with partial response) remaining on study for ≥ 6 months. CONCLUSION: ZD1839 was well tolerated, with DLT observed at a dose well above that at which antitumor activity was seen. Pharmacokinetic analysis confirmed that ZD1839 was suitable for administration as a once-daily oral tablet formulation. Phase II monotherapy and phase III combination trials in NSCLC are being conducted to investigate further the efficacy, tolerability, and optimal daily dose of ZD1839.