bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation of drug-montmorillonite UV-radiation protection compounds by gas-solid adsorption
Authors: del Hoyo C. , Vicente M. A. , Rives V. 
Published: July 2002

AbstractEthyl cinnamate/montmorillonite intercalation complexes were obtained by gaseous adsorption of the drug on the clay surface. They were characterized by powder X-ray diffraction, differential thermal and thermogravimetric analyses and by visible-UV and IR spectroscopies. It was found that after 1 day of adsorption, most of the drug enters the interlayer space of the clay by substitution of water molecules, and is removed only after heating at high temperature. In addition, a portion is physisorbed on the external surface of the crystallites, being removed easily below 100°C. The interlayer complex improves the protecting ability of the pure clay or the pure drug against ultraviolet radiation, specially in the so-called ‘C’ range (290–190 nm).
Clays and zeolite authigenesis in sediments from the flank of the Juan de Fuca Ridge
Authors: Buatier M. D. , Karpoff A. M. , Charpentier D. 
Published: July 2002

AbstractThis study focuses on the mineralogical and chemical analysis of sediments overlying basaltic basement through which seawater circulates (ODP Leg 168, flank of the Juan de Fuca Ridge). A SEM and TEM-EDX study of the authigenic clays and zeolites allowed the characterization of the hydrothermal phases and the determination of their mechanism of formation. Silicate authigenesis related to hydrothermal alteration of sediment was observed in the sediment layer just above basement at sites located >30 km from the ridge axis. This sediment alteration is particularly intense at Site 1031 where authigenic formation of Fe-Mg- rich smectites (montmorillonite and saponite) and zeolites occur, linked to the dissolution of biogenic calcite. Vertical advection of basement fluid through the sediment column is required to produce this alteration. This process is still active at Site 1031, based on systematic variations in porewater profiles and temperatures obtained from stable isotopic data on calcium carbonates, and the nature of authigenic minerals.
Primary zoning in pyrochlore group minerals from carbonatites
Authors: Hogarth D. D. , Williams C. T. , Jones P. 
Published: July 2002

AbstractPyrochlore group minerals have the general formula A16–xB16O48Z8–y·nH2O, with A mainly Na, Ca, Sr, REE, Th, U; B mainly Nb, Ta, Ti and Z being O, F, OH. In this study, pyrochlore specimens were examined from carbonatites at Argor, Carillon Dam, Chilwa Island, Fen, Lueshe, Oka, Mbeya, Meech Lake and Verity. Primary features include a background with little compositional variation, from core to rim, upon which are commonly superimposed narrow oscillatory zones, parallel to {111}. These zones are usually characterized by high Ta, in many cases coupled with U (here Argor, Meech Lake and Verity specimens), but Chilwa Island and Fen pyrochlores have little Ta and zonation is mainly by enrichment in Ce and Nb. Primary zonation may persist through high-temperature metamorphism (Meech Lake and Verity) and metamictization (Meech Lake). Oscillatory zones were generated by a disequilibrium system that cooled under tranquil conditions, signalling absence of magma turbulence and, in many cases, the end of crystal growth. Some fresh crystals (Oka, Fen) have no oscillatory zones, possibly the product of magma turbulence in space or time. Low-temperature effects may mimic those of primary high temperature and are especially characterized by replacement rims, pyrochlore-inpyrochlore veinlets and low A-ion totals (Carillon Dam, Lueshe, Myeba).
Hypogene violarite of exsolution origin from Mount Keith, Western Australia: field evidence for a stable pentlandite–violarite tie line
Authors: Grguric B. A. 
Published: July 2002

AbstractIn most documented occurrences, violarite (FeNi2S4) occurs as a product of the supergene alteration of primary pentlandite or millerite. Earlier experimental phase relations studies predicted the possible existence of a stable violarite–pentlandite tie line, though there has been little field evidence supporting this hypothesis, and the preferred topology in the Ni-Fe-S system involves a pyrite–millerite tie line. This paper documents the occurrence of violarite-pentlandite±pyrite assemblages which, on the basis of mineral chemistry and textural evidence, appear to be hypogene. Primary cobaltian violarite (with 2.1–13.2 wt.% Co) occurs as lamellae in pentlandite in the MKD5 nickel sulphide orebody at Mount Keith, central Western Australia. These lamellae are interpreted to be of exsolution origin. Cobalt is preferentially partitioned into violarite, resulting in high Ni:Co ratios in the associated pentlandite relative to pentlandite in violarite-free assemblages. Hypogene violarite-millerite±pentlandite assemblages were also noted. In all hypogene assemblages, violarite differs in both textural and mineral chemical characteristics from supergene violarite from the upper portions of the MKD5 orebody. The implications of the assemblages for the known low-temperature phase relations in the Ni-Fe-S-(Co) system are discussed.
REE -Sr-Ba minerals from the Khibina carbonatites, Kola Peninsula, Russia: their mineralogy, paragenesis and evolution
Authors: Zaitsev Anatoly N. , Wall Frances , Le Bas Michael J. 
Published: July 2002

AbstractCarbonatites from the Khibina Alkaline Massif (360–380 Ma), Kola Peninsula, Russia, contain one of the most diverse assemblages of REE minerals described thus far from carbonatites and provide an excellent opportunity to track the evolution of late-stage carbonatites and their sub-solidus (secondary) changes. Twelve rare earth minerals have been analysed in detail and compared with literature analyses. These minerals include some common to carbonatites (e.g. Ca-rare-earth fluocarbonates and ancylite-(Ce)) plus burbankite and carbocernaite and some very rare Ba,REE fluocarbonates.Overall the REE patterns change from light rare earth-enriched in the earliest carbonatites to heavy rare earth-enriched in the late carbonate-zeolite veins, an evolution which is thought to reflect the increasing ‘carbohydrothermal’ nature of the rock-forming fluid. Many of the carbonatites have been subject to sub-solidus metasomatic processes whose products include hexagonal prismatic pseudomorphs of ancylite-(Ce) or synchysite-(Ce), strontianite and baryte after burbankite and carbocernaite. The metasomatic processes cause little change in the rare earth patterns and it is thought that they took place soon after emplacement.
Seven new mutations in the nicotinamide adenine dinucleotide reduced–cytochrome b5 reductase gene leading to methemoglobinemia type I
Authors: Dekker Jan , Eppink Michel H. M. , van Zwieten Rob , de Rijk Thea , Remacha Angel F. , Law Lap Kay , Li Albert M. , Cheung Kam Lau , van Berkel Willem J. H. , Roos Dirk 
Published: July 2002

AbstractCytochrome b5 reductase (b5R) deficiency manifests itself in 2 distinct ways. In methemoglobinemia type I, the patients only suffer from cyanosis, whereas in type II, the patients suffer in addition from severe mental retardation and neurologic impairment. Biochemical data indicate that this may be due to a difference in mutations, causing enzyme instability in type I and complete enzyme deficiency or enzyme inactivation in type II. We have investigated 7 families with methemoglobulinemia type I and found 7 novel mutations in the b5R gene. Six of these mutations predicted amino acid substitutions at sites not involved in reduced nicotinamide adenine dinucleotide (NADH) or flavin adenine dinucleotide (FAD) binding, as deduced from a 3-dimensional model of human b5R. This model was constructed from comparison with the known 3-dimensional structure of pig b5R. The seventh mutation was a splice site mutation leading to skipping of exon 5 in messenger RNA, present in heterozygous form in a patient together with a missense mutation on the other allele. Eight other amino acid substitutions, previously described to cause methemoglobinemia type I, were also situated in nonessential regions of the enzyme. In contrast, 2 other substitutions, known to cause the type II form of the disease, were found to directly affect the consensus FAD-binding site or indirectly influence NADH binding. Thus, these data support the idea that enzyme inactivation is a cause of the type II disease, whereas enzyme instability may lead to the type I form.
BCR-ABL down-regulates the DNA repair protein DNA-PKcs
Authors: Deutsch Eric , Dugray Aymeric , AbdulKarim Bassam , Marangoni Elisabetta , Maggiorella Laurence , Vaganay Sabine , M'Kacher Radia , Rasy Setha Douc , Eschwege François , Vainchenker William , Turhan Ali G. , Bourhis Jean 
Published: July 2002

Abstract
This study demonstrates in both stable and inducible BCR-ABL–expressing hematopoietic cells a down-regulation of the major mammalian DNA repair protein DNA-PKcs by BCR-ABL. Similar results were found in BCR-ABL CD34+ cells from patients with chronic myelogenous leukemia (CML). DNA-PKcs down-regulation is a proteasome-dependent degradation that requires tyrosine kinase activity and is associated with a marked DNA repair deficiency along with increased sensitivity to ionizing radiation. The conjunction of a major DNA repair deficiency and a resistance to apoptosis, both induced by BCR-ABL, provides a new mechanism to explain how secondary genetic alterations can accumulate in CML, eventually leading to blast crisis. The down-regulation of DNA-PKcs was reversible in CD34+ CML cells suggesting that this approach might offer a novel and powerful therapeutic strategy in this disease, especially to delay the blast crisis.
βMinor-globin messenger RNA accumulation in reticulocytes governs improved erythropoiesis in β thalassemic mice after erythropoietin complementary DNA electrotransfer in muscles
Authors: Samakoglu Selda , Fattori Elena , Lamartina Stefania , Toniatti Carlo , Stockholm Daniel , Heard Jean Michel , Bohl Delphine 
Published: July 2002

AbstractMechanisms governing the induction of effective erythropoiesis in response to erythropoietin (Epo) oversecretion have been investigated in β thalassemic C57Bl/6Hbbth mice. Naked DNA encoding an expression vector for mouse Epo was introduced into skeletal muscles by electrotransfer. A transient increase of serum Epo concentrations with a proportional augmentation of hematocrit values was observed. Various parameters relevant to β thalassemia were surveyed in blood samples taken before treatment, at the peak of Epo secretion, and when the phenotype reverted to anemia. We measured globin messenger RNA (mRNA) levels in reticulocytes by real-time quantitative polymerase chain reaction, globin chain synthesis levels, and several indicators of erythrocyte membrane quality, including bound α chains, bound immunoglobulins, main protein components, and iron compartmentalization. Data indicated that high serum Epo levels primarily affect βminor-globin mRNA accumulation in reticulocytes. Other changes subsequent to intense Epo stimulation, like increased βminor/α-globin chain synthesis ratio, reduced levels of α chains and immunoglobulins bound to membranes, improved spectrin/band 3 ratio, increased red blood cell survival, and improved erythropoiesis appeared as consequences of increased βminor-globin mRNA levels. This conclusion is consistent with models postulating that intense Epo stimulation induces the expansion and differentiation of erythroid progenitors committed to fetal erythropoiesis. Although phenotypic correction was partial in mice, and comparable achievements will probably be more difficult to obtain in humans, naked DNA electrotransfer may provide a safe and low-cost method for reassessing the potentials of Epo as an inducer of fetal erythropoiesis reactivation in patients with β thalassemia.
Systemic circulation of poly(l-lysine)/DNA vectors is influenced by polycation molecular weight and type of DNA: differential circulation in mice and rats and the implications for human gene therapy
Authors: Ward Christopher M. , Read Martin L. , Seymour Leonard W. 
Published: July 2002

AbstractEffective gene therapy for diseases of the circulation requires vectors capable of systemic delivery. The molecular weight of poly(l-lysine) (pLL) has a significant effect on the circulation of pLL/DNA complexes in mice, with pLL211/DNA complexes displaying up to 20 times greater levels in the blood after 30 minutes compared with pLL20/DNA. It is shown that pLL20/DNA complexes fix mouse complement C3 in vitro, independent of immunoglobulin binding; are less soluble in the blood in vivo; bind erythrocytes; are rapidly removed by the liver, where they associate predominantly with Kupffer cells; and result in a rapid increase in hepatic leukocytes expressing high levels of complement receptor 3 (CR3). The circulation properties of these complexes are also dependent on the type of DNA used, with circular plasmid DNA complexes exhibiting increased circulation compared with linear DNA. PLL211/DNA complexes bind erythrocytes and associate with Kupffer cells but, in contrast, do not fix mouse complement in vitro and are unaffected by the type of DNA used. In rats, both types of complexes produce hematuria and are rapidly removed from the circulation. Correlation of in vivo and in vitro results suggests that the solubility of complexes in physiological saline and species-matched complement fixation and erythrocyte lysis may correlate with systemic circulation. Analysis using human blood in vitro shows no hemolysis, but both types of complexes fix complement and bind IgG, suggesting that pLL/DNA complexes may be rapidly cleared from the human circulation.
Durable engraftment of major histocompatibility complex–incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide
Authors: Luznik Leo , Jalla Sanju , Engstrom Laura W. , Iannone Robert , Fuchs Ephraim J. 
Published: July 2002

AbstractTreatment of leukemia by myeloablative conditioning and transplantation of major histocompatibility complex (MHC)–mismatched stem cells is generally avoided because of the high risk of graft rejection or lethal graft-versus-host disease (GVHD). This study shows that MHC-incompatible cells can engraft stably after nonmyeloablative conditioning with immunosuppressive chemotherapy and low-dose total body irradiation (TBI). Long-term mixed hematopoietic chimerism, clonal deletion of donor-reactive T cells, and bidirectional cytotoxic T-cell tolerance were achieved by transplanting MHC-mismatched marrow cells into recipients conditioned with pretransplantation fludarabine or cyclophosphamide (Cy), 50 to 200 cGy TBI on day −1, and Cy 200 mg/kg intraperitoneally on day 3. In this model, long-term donor chimerism was proportional to the dose of TBI or donor marrow cells. Pretransplantation fludarabine and posttransplantation Cy were both required for alloengraftment, but the drugs had additional effects. For example, fludarabine sensitized host stem cells to the toxicity of TBI, because animals conditioned with both agents had higher chimerism than animals conditioned with TBI alone (P &lt; .05). Also, posttransplantation Cy attenuated lethal and nonlethal GVH reactions, because F1 recipients of host-reactive, parental spleen cells survived longer (P &lt; .05) and had lower donor cell chimerism (P &lt; .01) if they received posttransplantation Cy than if they did not. Finally, delayed infusions of donor lymphocytes into mixed chimeras prolonged survival after leukemia challenge (P &lt; .0001) without causing lethal GVHD. These results indicate that stable engraftment of MHC-incompatible cells can be induced after fludarabine-based, nonmyeloablative conditioning and that it serves as a platform for adoptive immunotherapy with donor lymphocyte infusions.
Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor–positive human tumors
Authors: Masood Rizwan , Cai Jie , Zheng Tong , Smith D. Lynne , Hinton David R. , Gill Parkash S. 
Published: July 2002

AbstractAngiogenesis is required for the progression of tumors from a benign to a malignant phenotype and for metastasis. Malignant tumor cells secrete factors such as vascular endothelial growth factor (VEGF), which bind to their cognate receptors on endothelial cells to induce angiogenesis. Here it is shown that several tumor types express VEGF receptors (VEGFRs) and that inhibition of VEGF (VEGF antisense oligonucleotide AS-3) or VEGFRs (neutralizing antibodies) inhibited the proliferation of these cell lines in vitro. Furthermore, this effect was abrogated by exogenous VEGF. Thus, VEGF is an autocrine growth factor for tumor cell lines that express VEGFRs. A modified form of VEGF AS-3 (AS-3m), in which flanking 4 nucleotides were substituted with 2-O-methylnucleosides (mixed backbone oligonucleotides), retained specificity and was active when given orally or systemically in vitro and in murine tumor models. In VEGFR-2–expressing tumors, VEGF inhibition may have dual functions: direct inhibition of tumor cell growth and inhibition of angiogenesis.
A comparative evaluation of conventional and pretargeted radioimmunotherapy of CD20-expressing lymphoma xenografts
Authors: Press Oliver W. , Corcoran Melissa , Subbiah Krishnan , Hamlin Don K. , Wilbur D. Scott , Johnson Timothy , Theodore Louis , Yau Eric , Mallett Robert , Meyer Damon L. , Axworthy Don 
Published: July 2002

Abstract
Radioimmunotherapy with anti-CD20 monoclonal antibodies is a promising new treatment approach for patients with relapsed B-cell lymphomas. However, the majority of patients treated with conventional radiolabeled anti-CD20 antibodies eventually have a relapse because the low tumor-to-blood and tumor-to–normal organ ratios of absorbed radioactivity limit the dose that can be safely administered without hematopoietic stem cell support. This study assessed the ability of a streptavidin-biotin “pretargeting” approach to improve the biodistribution of radioactivity in mice bearing Ramos lymphoma xenografts. A pretargeted streptavidin-conjugated anti-CD20 1F5 antibody was infused, followed 24 hours later by a biotinylated N-acetylgalactosamine–containing “clearing agent” and finally 3 hours later by 111In-labeled DOTA-biotin. Tumor-to-blood ratios were 3:1 or more with pretargeting, compared with 0.5:1 or less with conventional 111In-1F5. Tumor-to–normal organ ratios of absorbed radioactivity up to 56:1 were observed with pretargeting, but were 6:1 or less with conventional 111In-1F5. Therapy experiments demonstrated that 400 μCi (14.8 MBq) or more of conventional 90Y-1F5 was required to obtain major tumor responses, but this dose was associated with lethal toxicity in 100% of mice. In marked contrast, up to 800 μCi (29.6 MBq)90Y-DOTA-biotin could be safely administered by the pretargeting approach with only minor toxicity, and 89% of the mice were cured. These data suggest that anti-CD20 pretargeting shows great promise for improving current therapeutic options for B-cell lymphomas and warrants further preclinical and clinical testing.
Effects of Long-Term Intravenous Ibandronate Therapy on Skeletal-Related Events, Survival, and Bone Resorption Markers in Patients With Advanced Multiple Myeloma
Authors: Menssen Hans D. , Sakalová Adriana , Fontana Aurélie , Herrmann Zuzana , Boewer Christian , Facon Thierry , Lichinitser Michail R. , Singer C.R.J. , Euller-Ziegler Liana , Wetterwald Marc , Fiere Denis , Hrubisko Mikulás , Thiel Eckhard , Delmas Pierre D. 
Published: July 2002

PURPOSE: Bisphosphonates have been found to reduce the incidence of skeletal-related events (SREs) in patients with multiple myeloma. This is the first double-blind, randomized, placebo-controlled study to assess the efficacy of ibandronate, a third-generation amino-bisphosphonate, in preventing SREs in advanced-stage multiple myeloma patients. PATIENTS AND METHODS: Patients with multiple myeloma stage II or III were randomly assigned to receive either ibandronate 2 mg or placebo as a monthly intravenous (IV) bolus injection for 12 to 24 months in addition to conventional chemotherapy. SREs such as peripheral pathologic or vertebral fractures, hypercalcemia, severe bone pain, and bone radiotherapy or surgery were analyzed. Bone-turnover markers were also studied. Finally, post hoc analyses of bone morbidity and survival were performed. RESULTS: Ninety-nine patients per treatment group were assessable for efficacy analysis. The occurrence of SRE per patient year and the time to first SRE were not significantly different between the two treatment groups. In overall evaluation, no differences were found between the treatment groups regarding bone pain, analgesic drug use, quality of life, and median survival (33.1 v 28.2 months, respectively). Explorative post hoc analyses revealed that ibandronate patients with strongly suppressed bone-turnover markers (≥ 30% and ≥ 50% mean reduction of serum osteocalcin and urinary C-terminal telopeptides) developed significantly less bone morbidity. Ibandronate was tolerated well during as many as 25 therapy cycles. CONCLUSION: Monthly injections of ibandronate 2 mg IV neither reduced bone morbidity nor prolonged survival in the overall population of stage II/III multiple myeloma patients.
Pilot Study of Iodine-131–Metaiodobenzylguanidine in Combination With Myeloablative Chemotherapy and Autologous Stem-Cell Support for the Treatment of Neuroblastoma
Authors: Yanik Gregory A. , Levine John E. , Matthay Katherine K. , Sisson James C. , Shulkin Barry L. , Shapiro Brahm , Hubers David , Spalding Susan , Braun Tom , Ferrara James L.M. , Hutchinson Raymond J. 
Published: July 2002

PURPOSE: The survival for children with relapsed or metastatic neuroblastoma remains poor. More effective regimens with acceptable toxicity are required to improve prognosis. Iodine-131–metaiodobenzylguanidine (131I-MIBG) selectively targets radiation to catecholamine-producing cells, including neuroblastoma cells. A pilot study was performed to examine the feasibility of a novel regimen combining 131I-MIBG and myeloablative chemotherapy with autologous stem-cell rescue. PATIENTS AND METHODS: Twelve patients with neuroblastoma were treated after relapse (five patients) or after induction therapy (seven patients). Eight patients had metastatic and four had localized disease at the time of therapy. All patients received 131I-MIBG 12 mCi/kg on day −21, followed by carboplatin (1,500 mg/m2), etoposide (800 mg/m2), and melphalan (210 mg/m2) administered from day −7 to day −4. Autologous peripheral-blood stem cells or bone marrow were infused on day 0. Engraftment, toxicity, and response rates were evaluated. RESULTS: The 131I-MIBG infusion and myeloablative chemotherapy were both well tolerated. Grade 2 to 3 oral mucositis was the predominant nonhematopoietic toxicity, occurring in all patients. The median times to neutrophil (≥ 0.5 × 103/μL) and platelet (≥ 20 × 103/μL) engraftment were 10 and 28 days, respectively. For the eight patients treated with metastatic disease, three achieved complete response and two had partial responses by day 100 after transplantation. CONCLUSION: Treatment with 131I-MIBG in combination with myeloablative chemotherapy and hematopoietic stem-cell rescue is feasible with acceptable toxicity. Future study is warranted to examine the efficacy of this novel therapy.