bluuebunny/crossref_metadata_2025 huggingface dataset:
Nematicidal metabolites produced by Photorhabdus luminescens (Enterobacteriaceae), bacterial symbiont of entomopathogenic nematodes
Authors: Hu Kaiji , Li Jianxiong , Webster John M.
Published: July 2002

The secondary metabolites, 3,5-dihydroxy-4-isopropylstilbene (ST) and indole,
from the culture filtrate of Photorhabdus luminescens MD, were shown to have
nematicidal properties. ST caused nearly 100% mortality of J4 and adults of
Aphelenchoides rhytium , Bursaphelenchus spp. and Caenorhabditis elegans at
100 mu g/ml, but had no effect on J2 of Meloidogyne incognita or infective
juveniles (IJ) of Heterorhabditis megidis at 200 mu g/ml. Indole was lethal
to several nematode species at 300 mu g/ml, and caused a high percentage of
Bursaphelenchus spp. (J4 and adults), M. incognita (J2) and Heterorhabditis
spp. (IJ) to be paralysed at 300, 100 and 400 mu g/ml, respectively. Both ST
and indole inhibited egg hatch of M. incognita . ST repelled IJ of some
Steinernema spp. but not IJ of Heterorhabditis spp., and indole repelled IJ
of some species of both Steinernema and Heterorhabditis . ST, but not
indole, was produced in nematode-infected larval Galleria mellonella after
24 h infection. Von Photorhabdus luminescens (Enterobacteriaceae), einem
Symbionten entomopathogener Nematoden gebildete nematizide Metaboliten - Es
wurde gezeigt, dass die Sekundarmetaboliten 3,5-Dihydroxy-4-isopropylstilben
(ST) und Indol aus dem Kulturfiltrat von Photorhabdus luminescens MD
nematizide Eigenschaften besassen. In einer Konzentration von 100 mu g/ml
verursachte ST eine fast 100%ige Sterblichkeit bei J4 und Adulten von
Aphelenchoides rhytium , Bursaphelenchus spp. und Caenorhabditis elegans ,
hatte aber bei 200 mu g/ml keine Wirkung auf J2 von Meloidogyne incognita
oder auf Infektionsjuvenile (IJ) von Heterorhabditis megidis . Bei 300 mu
g/ml war Indol fur etliche Nematodenarten todlich und fuhrte dazu, dass
Bursaphelenchus spp. (J4 and Adulte) bei 300, M. incognita (J2) bei 100, und
Heterorhabditis spp. (IJ) bei 400 mu g/ml zu einem grossen Teil gelahmt
wurden. ST und Indol behinderten beide das Schlupfen von M. incognita . ST
wirkte abstossend auf IJ einiger Steinernema -Arten aber nicht auf IJ von
Heterorhabditis spp., und Indol wirkte abstossend auf IJ einiger Arten der
beiden Gattungen Steinernema und Heterorhabditis . ST wurde in
nematoden-befallenen Larven von Galleria mellonella 24 h nach der Infektion
gebildet, Indol dagegen nicht.
THE STUDY OF LIFE BOREDOM
Authors: Bargdill Richard
Published: July 2002

This article extends the study of a phenomenological investigation (Bargdill, R. W., 2000) in which six participants wrote protocols and gave interviews describing the experience of being bored with their lives. This study found that the participants gradually became bored after they had compromised their life-projects for less desired projects. The participants felt emotionally ambivalent because they were thematically angry with others involved in their compromises while being pre-reflectively angry with themselves. The participants non-thematically adopted passive and avoidant stances toward their lives that allowed their boredom to spread to more aspects of their lives. The participants' boredom led them to identity issues because they no longer were actively working toward projects. They felt empty and apathetic because they felt every action led to boredom, and thus action was futile. Preliminary distinctions between the experience of life boredom and depression are considered.
Significance of random illite-vermiculite mixed layers in Pleistocene sediments of the northwestern Atlantic Ocean
Authors: Vanderaveroet P. , Bout-roumazeilles V. , Fagel N. , Chamley H. , Deconinck J. F.
Published: July 2002

The clay mineralogy of Pleistocene sediments of eleven sediment cores at three ODP sites from 30°N to 60°N northwestern Atlantic Ocean has been investigated. The sediments are characterized by the presence of random illite-vermiculite mixed layers (I-V) (up to 32% of the clay mineral assemblage). The I-V clays are much more abundant during interglacial periods than during glacial ones. They are attributed to detrital supply through erosion of high-latitude continental areas from which they are derived mainly from chemical weathering of micaceous phyllosilicates. Their spatial distribution and the specific conditions for their formation through weathering suggest that I-V mixed layers are mainly derived from the Canadian Shield. They were transported from their source to marine deposition areas by rivers, deep water masses or nepheloid layers. Due to the specific conditions required for the formation of I-V, its occurrence and abundance are used as a palaeoclimate and palaeocirculation proxy for northwestern Atlantic Pleistocene sediment.
An experimental alteration of montmorillonite to a di + trioctahedral smectite assemblage at 100 and 200°C
Authors: Beaufort D. , Berger G. , Lacharpagne J. C. , Meunier A.
Published: July 2002

Hydrothermal experiments were performed at 100 and 200°C and at different clay:water ratios in order to investigate the transformation of smectitic layers during the alteration of a montmorillonitic starting material. This study focused on three phenomena: (1) the amount and localization of charge within the layer of the newly-formed dioctahedral smectite; (2) the stacking of low- and high-charge layers in the dioctahedral smectitic material; and (3) the neoformation of trioctahedral smectites.

In all of the runs, the formation of beidellite from montmorillonite induced morphological changes in clay particles which suggests a reaction proceeding by a dissolution-crystallization mechanism. Illite layers were detected in K-saturated montmorillonite runs after the transformation of ∼50% of the starting montmorillonite into beidellite (i.e. after 5 months of reaction with distilled water at 200°C). These illite layers were interstratified with both high-charge and low-charge dioctahedral smectites in a hypothetical three-component mixed-layer mineral.
Cottonseed oil bleaching by acid-activated montmorillonite
Authors: Falaras P. , Kovanis I. , Lezou F. , Seiragakis G.
Published: July 2002

A progressive decrease in cation exchange capcity (CEC) values was observed by treating Ca-montmorillonite with sulphuric acid solutions and this can be understood in terms of the layered structure of the clay. Elemental analysis showed that moderate activation occurred and only 25–30% of the octahedral cations were removed. At the same time the total surface area and the clay acidity increase. X-ray and FTIR data confirmed that acid activation affects both the octahedral and the tetrahedral sheets. The efficiency of acid-activated montmorillonite for the bleaching of cottonseed oil was investigated. The differences in bleaching efficiency appeared to be due to differences in the physical and chemical properties of the bleaching media. The oil acid value was not affected by the bleaching procedure but a slight shift in the absorption maximum of the bleached cottonseed oil was observed. Medium activation of the clay (treatment of Ca-montmorillonite with 4 N H2SO4) was the most effective in bleaching the cottonseed oil, resulting in the best colour index and the lowest peroxide value. A linear dependence of the bleaching efficiency on the clay surface area and acidity was observed. The role of the increased Bronsted acidity is also discussed.
Adsorption of DL-alanine by allophane: effect of pH and unit particle aggregation
Authors: Hashizume H. , Theng B. K. G.
Published: July 2002

The adsorption of DL-alanine at pH 4, 6 and 8 by a soil allophane has been determined. Two sets of experiments were carried out: (1) in which the allophane had been kept in a moist state throughout; and (2) in which the mineral had previously been dried at 50°C. In both instances, the adsorption isotherms showed three distinct regions as the concentration of alanine in solution was increased: (1) an initial, nearly linear, rise at low equilibrium concentrations; (2) a levelling off to a plateau at intermediate concentrations; and (3) a steep linear increase at high concentrations. For comparable concentrations of alanine in solution, adsorption decreased in the order pH 6 > pH 8 > pH 4. Irrespective of pH, however, more alanine was adsorbed by the ‘wet’ allophane than by its ‘dry’ counterpart. These observations are interpreted in terms of the morphology and aggregation of allophane unit particles together with the pH-dependent charge characteristics of allophane and alanine. The results are compared with published data on the adsorption of alanine by montmorillonite.
MappingREEdistribution in scheelite using luminescence
Authors: Brugger J. , Bettiol A. A. , Costa S. , Lahaye Y. , Bateman R. , Lambert D. D. , Jamieson D. N.
Published: July 2002

In situlaser ablation high resolution ICP-MS analyses of scheelite from hydrothermal veins at the Archaean Mt. Charlotte gold deposit (Western Australia) show inhomogeneousREEdistribution at small scale (<100 μm). In a limited number of samples, variations of the cathodoluminescence (CL) colours from blue to yellow are linked to theREEcontent of scheelite, and reveal oscillatory zoning of theREEwith zone widths between 1 μm and 100 μm. However, CL failed to reveal the zoning in most inhomogeneous scheelite samples. A nuclear microprobe has been used to characterize the distribution ofREEin these samples. No reasonable map for the distribution ofREEcould be obtained by particle induced X-ray emission, because of interferences withW-Llines. However, monochromatic ionoluminescence (IL) maps collected at the wavelength of the mainREE3+luminescence peaks revealed oscillatory zoning. Therefore, IL is a powerful tool for mapping the distribution ofREEin natural scheelite. Monochromatic IL maps allow us to determine the nature of the inhomogeneous distribution ofREEin scheelite, fundamental information for using theREEin this mineral as a marker for the chemistry of ore-forming fluids, and for interpreting Sm-Nd isotopic data.
Chevkinite-group minerals from salic volcanic rocks of the East African Rift
Authors: Macdonald R. , Marshall A. S. , Dawson J. B. , Hinton R. W. , Hill P. G.
Published: July 2002

Electron microprobe analyses are presented of chevkinite-group minerals occurring as microphenocrysts in peralkaline rhyolites of the Greater Olkaria Volcanic Complex (Kenya) and as a groundmass phase in a peralkaline quartz trachyte lava from the Tarosero volcano (Tanzania), both in the East African Rift Valley. Their compositions conform closely to the formula: (REE, Ca, Th)4Fe2+(Fe2+, Al, Ti, Zr, Nb)2Ti2(Si4O22). Compared to published analyses of chevkinite-group minerals, the Olkaria phases are relatively enriched in Nb and theLREE; the Tarosero phase is more calcic and relatively Zr- and Nb-rich. The main substitution in theAsite at Olkaria is Ca ⇌ Ce. The overall charge-balancing substitution seems to be (McDowell, 1979):

Phenocryst/glass ratios are presented for Nb,REE, Sr, Th, U and Y in two, and Ba, Zr and Hf in one, Kenyan samples. Partition coefficients are lower in the more peralkaline rock, with the exception of Sr, which is higher. The lower values are consistent with a lower degree of polymerization of more peralkaline melts. The higher Sr value may be a function of Sr partitioning into phenocryst phases coexisting with chevkinite.
Recommended nomenclature for zeolite minerals: report of the subcommittee on zeolites of the International Mineralogical Association, Commission on New Minerals and Mineral Names
Authors: Coombs Douglas S. , Alberti Alberto , Armbruster Thomas , Artioli Gilberto , Colella Carmine , Galli Ermanno , Grice Joel D. , Liebau Friedrich , Mandarino Joseph A. , Minato Hideo , Nickel Ernest H. , Passaglia Elio , Peacor Donald R. , Quartieri Simona , Rinaldi Romano , Ross Malcolm , Sheppard Richard A. , Tillmanns Ekkehart , Vezzalini Giovanna
Published: July 2002

This report embodies recommendations on zeolite nomenclature approved by the International Mineralogical Association Commission on New Minerals and Mineral Names. In a working definition of a zeolite mineral used for this review, interrupted tetrahedral framework structures are accepted where other zeolitic properties prevail, and complete substitution by elements other than Si and Al is allowed. Separate species are recognized in topologically distinctive compositional series in which different extra-framework cations are the most abundant in atomic proportions. To name these, the appropriate chemical symbol is attached by a hyphen to the series name as a suffix except for the names harmotome, pollucite and wairakite in the phillipsite and analcime series. Differences in spacegroup symmetry and in order—disorder relationships in zeolites having the same topologically distinctive framework do not in general provide adequate grounds for recognition of separate species. Zeolite species are not to be distinguished solely on Si : Al ratio except for heulandite (Si : Al < 4.0) and clinoptilolite (Si : Al ⩾ 4.0). Dehydration, partial hydration, and over-hydration are not sufficient grounds for the recognition of separate species of zeolites. Use of the term ‘ideal formula’ should be avoided in referring to a simplified or averaged formula of a zeolite.

Newly recognized species in compositional series are as follows: brewsterite-Sr, -Ba; chabazite-Ca, - Na, -K; clinoptilolite-K, -Na, -Ca; dachiardite-Ca, -Na; erionite-Na, -K, -Ca; faujasite-Na, -Ca, -Mg; ferrierite-Mg, -K, -Na; gmelinite-Na, -Ca, -K; heulandite-Ca, -Na, -K, -Sr; levyne-Ca, -Na; paulingite-K, -Ca; phillipsite-Na, -Ca, -K; stilbite-Ca, -Na.

Key references, type locality, origin of name, chemical data, IZA structure-type symbols, space-group symmetry, unit-cell dimensions, and comments on structure are listed for 13 compositional series, 82 accepted zeolite mineral species, and three of doubtful status. Herschelite, leonhardite, svetlozarite, and wellsite are discredited as mineral species names. Obsolete and discredited names are listed.
The structure of antimonian dussertite and the role of antimony in oxysalt
minerals
Authors: Kolitsch U. , Slade P. G. , Tiekink E. R. T. , Pring A.
Published: July 2002

The structure of antimonian dussertite, (AsO4)2(OH,H2O)6,
has been refined in space group R3̄m with
a 7.410(3), c 17.484(4)
Å, Z = 3, to R = 3.2 % and
Rw = 3.7 % using 377 observed
reflections with I ≥ 3 σ(I).
The structure is of the alunite-type and consists of sheets of corner-sharing
(Fe3+,Sb5+)O6
octahedra parallel to (0001). The substitution of Sb5+ for
Fe3+, and not for As5+, is
unambiguously demonstrated not only by the structure refinement but also by
electron microprobe analyses and crystal-chemical considerations. The
icosahedrally coordinated Ba cations occupy cavities between pairs of octahedral
sheets and are surrounded by six O atoms from the AsO4
tetrahedra and six O atoms from the
(Fe3+,Sb5+)O6
octahedra. The mean bond lengths for the various coordination polyhedra are As-O
1.684(3) Å, (Fe,Sb)-O 2.004(1) Å, and Ba-O 2.872(2) Å. A hydrogen-bonding network
is modelled using bond-valence calculations. The dussertite sample investigated is
the first member of the crandallite group found to contain substantial
Sb.
Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-transretinoic acid
Authors: Douer Dan , Estey Elihu , Santillana Sergio , Bennett John M. , Lopez-Bernstein Gabriel , Boehm Kristi , Williams Tony
Published: July 2002

A novel intravenous liposomal formulation of all-transretinoic acid (ATRA) was evaluated in 69 patients with acute promyelocytic leukemia (APL): 32 new diagnoses, 35 relapses, and 2 oral ATRA failures. Liposomal ATRA (90 mg/m2) was administered every other day until complete remission (CR) or a maximum of 56 days. Treatment following CR was liposomal ATRA with or without chemotherapy. In an intent-to-treat (ITT) analysis of all patients, CR rates were 62%, 70%, and 20% in newly diagnosed, group 1 first relapses (ATRA naive or off oral ATRA more than or equal to 1 year), or group 2 relapses (second or subsequent relapse or first relapses off oral ATRA less than 1 year), respectively. In 56 evaluable patients (receiving 4 or more doses), CR rates for the same groups were 87% (20 of 23), 78% (14 of 18), and 23% (3 of 13). Remission failure in newly diagnosed patients was not from resistant disease. Several patients in CR became polymerase chain reaction (PCR) negative for promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARα) after liposomal ATRA alone. Toxicity was generally mild, most commonly headaches (67.5%). Eighteen patients (26%) had ATRA syndrome develop during induction. One-year survival of ITT patients was 62%, 56%, and 20% for newly diagnosed, group 1, and group 2, respectively. The medium duration of CR has not yet been reached and was 18 and 5.5 months in the same groups. These results demonstrate that liposomal ATRA is effective in inducing CR in newly diagnosed or group 1 APL patients. It provides a reliable dosage of ATRA for patients with APL unable to swallow or absorb medications and can induce molecular remissions without chemotherapy.
Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia
Authors: Meshinchi Soheil , Woods William G. , Stirewalt Derek L. , Sweetser David A. , Buckley Jonathan D. , Tjoa Thomas K. , Bernstein Irwin D. , Radich Jerald P.
Published: July 2002

The Flt3 gene encodes a tyrosine kinase receptor that regulates proliferation and differentiation of hematopoietic stem cells. An internal tandem duplication of the Flt3 gene (Flt3/ITD) has been reported in acute myelogenous leukemia (AML) and may be associated with poor prognosis. We analyzed diagnostic bone marrow specimens from 91 pediatric patients with AML treated on Children's Cancer Group (CCG)-2891 for the presence of the Flt3/ITD and correlated its presence with clinical outcome. Fifteen of 91 samples (16.5%) were positive for the Flt3/ITD. Flt3/ITD-positive patients had a median diagnostic white count of 73 800 compared with 28 400 for the Flt3/ITD-negative patients (P = .05). The size of the duplication ranged from 21 to 174 base pairs (bp). Nucleotide sequencing of the abnormal polymerase chain reaction products demonstrated that all duplications involved exon 11 of theFlt3 gene and also preserved the reading frame. Lineage restriction analysis revealed that Flt3/ITD was not present in the lymphocytes, suggesting a lack of stem cell involvement for this mutation. None of the Flt3/ITD-positive patients had unfavorable cytogenetic markers, and there was no predominance of a particular FAB class. The remission induction rate was 40% in Flt3/ITD-positive patients compared with 74% in Flt3/ITD-negative ones (P = .005). The Kaplan-Meier estimates of event-free survival at 8 years for patients with and without Flt3/ITD were 7% and 44%, respectively (P = .002). Multivariate analysis demonstrated that presence of the Flt3/ITD was the single most significant, independent prognostic factor for poor outcome (P = .009) in pediatric AML.
Functional correction of FA-C cells withFANCC suppresses the expression of interferon γ–inducible genes
Authors: Fagerlie Sara R. , Diaz Jane , Christianson Tracy A. , McCartan Kelli , Keeble Winifred , Faulkner Gregory R. , Bagby Grover C.
Published: July 2002

Because hematopoietic cells derived from Fanconi anemia (FA) patients of the C-complementation group (FA-C) are hypersensitive to the inhibitory effects of interferon γ (IFNγ), the products of certain IFNγ-inducible genes known to influence hematopoietic cell survival were quantified. High constitutive expression of the IFNγ-inducible genes, IFN-stimulated gene factor 3 gamma subunit (ISGF3γ), IFN regulatory factor-1 (IRF-1), and the cyclin-dependent kinase inhibitor p21WAF1 was found inFANCC mutant B lymphoblasts, low-density bone marrow cells, and murine embryonic fibroblasts. Paradoxically, these cells do not activate signal transducer and activator of transcription (STAT) 1 properly. In an attempt to clarify mechanisms by which FA-C cells overexpress IFNγ-inducible genes in the face of defective STAT1 phosphorylation, it was reasoned that decreased levels of activated STAT1 might result in reduced expression of a hematopoietic IFNγ-responsive protein that normally modulates expression of other IFNγ-responsive genes. Levels of the IFNγ-inducible factor IFN consensus sequence binding protein (ICSBP), a negative trans-acting regulator of some IFNγ-inducible genes, were quantified. ICSBP levels were reduced in FA-C B lymphoblasts and MEFs. However, enforced expression of ICSBP failed to down-regulate IRF-1, ISGF3γ, and p21WAF1. Thus, the FANCC protein functions to modulate expression of a family of genes that in normal cells are inducible only by specific environmental cues for apoptosis or mitogenic inhibition, but it does so independently of the classic IFN-STAT1 pathway and is not the direct result of reduced ICSBP expression.
Loss of red cell A, B, and H antigens is frequent in myeloid malignancies
Authors: Bianco Tina , Farmer Belinda J. , Sage Robert E. , Dobrovic Alexander
Published: July 2002

Loss of A, B, and H antigens from the surface of red blood cells has been a recurrent observation in patients with hematologic malignancy, particularly those malignancies in which the myeloid lineage is involved. To better understand this phenomenon, a 2-color flow cytometric method was developed to determine quantitative and qualitative alterations of A, B, and H antigens in patients with myeloid malignancies. Characteristic patterns, dependent on the genotype, were seen for healthy individuals from each of the blood groups. Fifty-five percent (16/29) of patients of blood group A, B, or AB had a proportion of red cells with decreased expression of A or B antigens compared with no changes in 127 healthy A, B, and AB individuals. In most cases, the changes were not detected by routine serologic typing. The loss of A or B antigens was the primary change in 28% (8/29) of patients. In 17% (5/29) of patients, loss of A or B antigens was an indirect consequence of loss of the precursor H antigen. Alterations involving both the H and the A or B antigens were seen in 10% (3/29) of patients. Loss of H was also detected in 21% (6/28) of group O patients whereas none of 51 healthy O individuals showed changes. Alterations of ABO antigens can now be considered a common event in myeloid malignancy.
Melphalan and purine analog–containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation
Authors: Giralt Sergio , Thall Peter F. , Khouri Issa , Wang Xuemei , Braunschweig Ira , Ippolitti Cindy , Claxton David , Donato Michele , Bruton Jill , Cohen Agueda , Davis Marilyn , Andersson Borje S. , Anderlini Paolo , Gajewski James , Kornblau Steven , Andreeff Michael , Przepiorka Donna , Ueno Naoto T. , Molldrem Jeff , Champlin Richard
Published: July 2002

A reduced-intensity preparative regimen consisting of melphalan and a purine analog was evaluated for allogeneic transplantation in 86 patients who had a variety of hematologic malignancies and were considered poor candidates for conventional myeloablative therapies because of age or comorbidity. Seventy-eight patients received fludarabine 25 mg/m2 daily for 5 days in combination with melphalan 180 mg/m2 (n = 66) or 140 mg/m2 (n = 12). Eight patients received cladribine 12 mg/m2 continuous infusion for 5 days with melphalan 180 mg/m2. The median age was 52 years (range, 22-70 years). Disease status at transplantation was either first remission or first chronic phase in 7 patients, untreated first relapse or subsequent remission in 16 patients, and refractory leukemia or transformed chronic myelogenous leukemia in 63 patients. Nonrelapse mortality rates on day 100 were 37.4% for the fludarabine/melphalan combination and 87.5% for the cladribine/melphalan combination. The median percentage of donor cells at 1 month in 75 patients was 100% (range, 0%-100%). The probability of grade 2-4 and 3-4 acute graft-versus-host disease was 0.49 (95% CI, 0.38-0.60) and 0.29 (95% CI, 0.18-0.41), respectively. Disease-free survival at 1 year was 57% for patients in first remission or chronic phase and 49% for patients with untreated first relapse or in a second or later remission. On multivariate analysis the strongest predictor for disease-free survival was a good or intermediate risk category. In summary, fludarabine/melphalan combinations are feasible in older patients with associated comorbidities, and long-term disease control can be achieved with reduced-intensity conditioning in this population.
Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans
Authors: Sawano Asako , Iwai Shinobu , Sakurai Yoshiko , Ito Mikito , Shitara Kenya , Nakahata Tatsutoshi , Shibuya Masabumi
Published: July 2002

Flt-1, also known as vascular endothelial growth factor receptor 1 (VEGFR-1), is a high-affinity tyrosine kinase receptor for VEGF and is expressed almost exclusively on vascular endothelial cells. As an exception, Flt-1 transcript was recently found to be expressed in human peripheral blood monocytes. However, the protein of the Flt-1 receptor on the cell surface of monocytes is yet to be identified, and whether the Flt-1 protein is expressed during the differentiation of monocyte-macrophage lineage cells has not been examined. Using monoclonal antibodies against 2 different antigenic epitopes on the Flt-1 extracellular domain, this study found that the major population of the monocyte-marker CD97+ cells in human peripheral blood express Flt-1 as a cell surface molecule. VEGFR-2 (KDR/Flk-1) was not expressed at detectable levels in these cells. An Flt-1 neutralizing monoclonal antibody significantly suppressed VEGF-induced migration of the monocytes, suggesting an important role for Flt-1 in the biologic function of monocytes. Furthermore, CD34+cells in human cord blood, originally negative for the Flt-1 expression, differentiated into Flt-1+ cells in association with the appearance of monocyte-macrophage markers after a 2-week culture in the presence of hematopoietic cytokines. In addition, the Flt-1+CD11b+ cell fraction from CD34+ cells was found to efficiently differentiate into multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and osteoclast differentiation factor. These results strongly suggest that Flt-1 is a novel cell surface marker as well as a biologically functional molecule for monocyte-macrophage lineages in humans.
Transcobalamin codon 259 polymorphism in HT-29 and Caco-2 cells and in Caucasians: relation to transcobalamin and homocysteine concentration in blood
Authors: Namour Farès , Olivier Jean-Luc , Abdelmouttaleb Idrissia , Adjalla Charles , Debard Renée , Salvat Colette , Guéant Jean-Louis
Published: July 2002

Transcobalamin (TC) is the plasma transporter that delivers vitamin B12 to cells. We have already reported that HT-29 and Caco-2 cells secrete different TC variants. HT-29 secretes 2 TC isoproteins (codon 259-Pro/Arg [259-P/R]), exhibiting unequal concentrations (TC 259-P > TC 259-R), and Caco-2 cells only secrete the phenotype 259-R. We investigated the relation between phenotypic and genetic TC polymorphism in HT-29 cells transfected with Caco-2 TC complementary DNA and in 159 healthy Caucasians. We found that codon 259-R is buried and, thus, the genetic polymorphism provides no explanation why the TCs from HT-29 and Caco-2 cells have different isoelectric points in nondenaturing isoelectric focusing (IEF). The newly translated TC in HT-29 cells from the Caco-2 complementary DNA recombinant plasmid had the same isoelectric point as the TC constitutively expressed in HT-29 cells, suggesting that TC phenotypic variability involves a specific cell folding of the protein. The codon 259 polymorphism was found to have a biallelic distribution: homozygotes P = 34.6%, heterozygotes R/P = 47.8%, and homozygotes R = 17.6%. In heterozygous samples, the IEF showed that the TC 259-P/TC 259-R ratio = 1.6. The blood apo-TC concentration of 259-P homozygous Caucasians was significantly higher than that of homozygous 259-R (P < .0001) and heterozygous (P < .0006) Caucasians. The heterozygotes 259-R/P had homocysteine concentration significantly higher than the homozygotes 259-R and 259-P (P = .02 and P = .01, respectively). In conclusion, TC codon-259 polymorphism affects TC plasma concentration and may interfere in vitamin B12cellular availability and homocysteine metabolism.
Long-term use of anagrelide in young patients with essential thrombocythemia
Authors: Storen Elizabeth C. , Tefferi Ayalew
Published: July 2002

Anagrelide is a novel platelet-lowering agent that has recently been approved for use in essential thrombocythemia (ET) and related disorders. Short-term drug efficacy and toxicity data have previously been presented. The purpose of this study was to obtain additional information regarding long-term anagrelide use. This is a retrospective series of 35 young patients (17 to 48 years) with ET who received anagrelide treatment before 1992. Initial drug dosage ranged between 1 and 10 mg/d, and the median maintenance dosage was 2.5 mg/d. The overall initial response rate of 94% included 74% complete remissions and 20% partial remissions. Of the 33 responding patients, 27 (82%) remained on anagrelide therapy for a median of 10.8 years (range, 7 to 15.5). Of these, 66% maintained a complete and 34% a partial remission over the study period. In general, the reporting of somatic side effects decreased over time, and anemia was the only new side effect that emerged after long-term therapy. Eight patients (24%) experienced a more than 3 g/dL decrease in hemoglobin level. Despite active therapy, 20% of the patients experienced a total of 10 thrombotic episodes, and a similar proportion experienced major hemorrhagic events. All thrombohemorrhagic complications occurred at a platelet count of more than 400 × 109/L. It is concluded that long-term treatment of ET with anagrelide is associated with decreased reporting of initial side effects and the development of mild-to-moderate anemia. Complete normalization of platelet counts may be needed to minimize residual thrombohemorrhagic risk during therapy.
Induction of cytomegalovirus (CMV)–specific T-cell responses using dendritic cells pulsed with CMV antigen: a novel culture system free of live CMV virions
Authors: Peggs Karl , Verfuerth Stephanie , Mackinnon Stephen
Published: July 2002

Recipients of allogeneic transplants are at risk of cytomegalovirus (CMV) infection and disease during the period of immune compromise after transplantation. The limitations of current antiviral pharmacotherapy have led to attempts to develop alternative strategies for preventing or treating CMV infection, such as adoptive transfer of donor-derived virus-specific T cells. Methods for generating CMV-specific T cells either use live CMV to infect autologous antigen-presenting cells (APCs) or require some knowledge of the immunodominant peptides involved in the immune response. A novel culture system was developed that does not use live virions and in which the APCs are monocyte-derived dendritic cells (DCs). APCs were pulsed with CMV antigen and cocultured with autologous peripheral blood lymphocytes from donors seropositive for CMV. The culture-output cells consisted of both CD4- and CD8-expressing T cells. Proliferation, as determined by a tritium-thymidine–incorporation assay, showed significant CMV-antigen specificity in cultures from 15 of 15 donors seropositive for CMV. In cytotoxicity assays, cytotoxic T lymphocytes from 10 of 12 cocultures specifically lysed autologous CMV-infected fibroblasts or DCs but not HLA-mismatched or uninfected target cells, and this activity was shown to be blocked by HLA class 1 blocking antibodies. T-cell–receptor spectratyping of cells from the cultures typically showed complex size-distribution patterns, with all size classes of a normal preculture distribution present. However, a few size-class peaks were expanded compared with the preculture patterns and these may have represented expansions of CMV-specific T-cell clones. Advantages of this culture system are that it requires no live virions and no detailed knowledge of the antigenic peptides involved and it is applicable to CMV-seropositive donors of any HLA type.
IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation
Authors: Mackall Crystal L. , Fry Terry J. , Bare Cathy , Morgan Paul , Galbraith Anne , Gress Ronald E.
Published: July 2002

Thymic-dependent differentiation of bone marrow (BM)-derived progenitors and thymic-independent antigen-driven peripheral expansion of mature T cells represent the 2 primary pathways for T-cell regeneration. These pathways are interregulated such that peripheral T-cell expansion is increased in thymectomized versus thymus-bearing hosts after bone marrow transplantation (BMT). This study shows that this interregulation is due to competition between progeny of these 2 pathways because depletion of thymic progeny leads to increased peripheral expansion in thymus-bearing hosts. To test the hypothesis that competition for growth factors modulates the magnitude of antigen-driven peripheral expansion during immune reconstitution in vivo, a variety of T-cell active cytokines were administered after BMT. Of the cytokines (interleukins) tested (IL-3, IL-12, IL-6, IL-2, and IL-7), IL-2 modestly increased peripheral expansion in the face of increasing numbers of thymic emigrants, whereas IL-7 potently accomplished this. This report also demonstrates that the beneficial effect of IL-7 on immune reconstitution is related to both increases in thymopoiesis as well as a direct increase in the magnitude of antigen-driven peripheral expansion. Therefore, the administration of exogenous IL-7, and to a lesser extent IL-2, abrogates the down-regulation in antigen-driven peripheral expansion that occurs in thymus-bearing hosts after BMT. These results suggest that one mechanism by which T-cell–depleted hosts may support antigen-driven T-cell expansion in vivo is via an increased availability of T-cell–active cytokines to support clonal expansion.
ARG tyrosine kinase activity is inhibited by STI571
Authors: Okuda Keiko , Weisberg Ellen , Gilliland D. Gary , Griffin James D.
Published: July 2002

The tyrosine kinase inhibitor STI571 inhibits BCR/ABL and induces hematologic remission in most patients with chronic myeloid leukemia. In addition to BCR/ABL, STI571 also inhibits v-Abl, TEL/ABL, the native platelet-derived growth factor (PDGF)β receptor, and c-KIT, but it does not inhibit SRC family kinases, c-FMS, FLT3, the epidermal growth factor receptor, or multiple other tyrosine kinases. ARG is a widely expressed tyrosine kinase that shares substantial sequence identity with c-ABL in the kinase domain and cooperates with ABL to regulate neurulation in the developing mouse embryo. As described here, ARG has recently been implicated in the pathogenesis of leukemia as a fusion partner of TEL. A TEL/ARG fusion was constructed to determine whether ARG can be inhibited by STI571. When expressed in the factor-dependent murine hematopoietic cell line Ba/F3, the TEL/ARG protein was heavily phosphorylated on tyrosine, increased tyrosine phosphorylation of multiple cellular proteins, and induced factor-independent proliferation. The effects of STI571 on Ba/F3 cells transformed with BCR/ABL, TEL/ABL, TEL/PDGFβR, or TEL/ARG were then compared. STI571 inhibited tyrosine phosphorylation and cell growth of Ba/F3 cells expressing BCR/ABL, TEL/ABL, TEL/PDGFβR, and TEL/ARG with an IC50 of approximately 0.5 μM in each case, but it had no effect on untransformed Ba/F3 cells growing in IL-3 or on Ba/F3 cells transformed by TEL/JAK2. Culture of TEL/ARG-transfected Ba/F3 cells with IL-3 completely prevented STI571-induced apoptosis in these cells, similar to what has been observed with BCR/ABL- or TEL/ABL-transformed cells. These results indicate that ARG is a target of the small molecule, tyrosine kinase inhibitor STI571.
Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia
Authors: Granziero Luisa , Ghia Paolo , Circosta Paola , Gottardi Daniela , Strola Giuliana , Geuna Massimo , Montagna Licia , Piccoli Paola , Chilosi Marco , Caligaris-Cappio Federico
Published: July 2002

In B-cell chronic lymphocytic leukemia (B-CLL), defective apoptosis causes the accumulation of mature CD5+ B cells in lymphoid organs, bone marrow (BM), and peripheral blood (PB). These cells are the progeny of a proliferating pool that feeds the accumulating compartment. The authors sought to determine which molecular mechanisms govern the proliferating pool, how they relate to apoptosis, and what the role is of the microenvironment. To begin to resolve these problems, the expression and modulation of the family of inhibitor of apoptosis proteins (IAPs) were investigated, with consideration given to the possibility that physiological stimuli, such as CD40 ligand (CD40L), available to B cells in the microenvironment, might modulate IAP expression. The in vitro data on mononuclear cells from PB or BM of 30 patients demonstrate that B-CLL cells on CD40 stimulation express Survivin and that Survivin is the only IAP whose expression is induced by CD40L. Through immunohistochemistry, in vivo Survivin expression in lymph node (LN) and BM biopsies was evaluated. In reactive LN, Survivin was detected only in highly proliferating germinal center cells. In LN from patients with B-CLL, Survivin was detected only in pseudofollicles. Pseudofollicle Survivin+ cells were actively proliferating and, in contrast to Survivin+ B cells found in normal GC, were Bcl-2+. In B-CLL BM biopsies, CD5+, Survivin+ cells were observed in clusters interspersed with T cells. These findings establish that Survivin controls the B-CLL proliferative pool interfacing apoptosis and that its expression may be modulated by microenvironmental stimuli.
CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia
Authors: Ibrahim Sherif , Keating Michael , Do Kim-Anh , O'Brien Susan , Huh Yang O. , Jilani Iman , Lerner Susan , Kantarjian Hagop M. , Albitar Maher
Published: July 2002

CD38 is a transmembrane glycoprotein expressed on the surface of leukemic cells in a significant percentage of patients with B-cell chronic lymphocytic leukemia (B-CLL). A recent study suggested that CD38 expression has prognostic value in CLL. Peripheral blood samples from 218 patients with B-CLL were analyzed by flow cytometry for CD38 expression on CD5/19+ leukemic cells. Various patient characteristics were studied including age, sex, Rai and Binet stages, splenomegaly, hepatomegaly, hemoglobin (Hgb) level, β-2 microglobulin (β2M) level in the serum, number of nodal sites involved with disease, and length of survival. The Kaplan-Meier method was used to construct survival curves, and the log-rank statistic was used to compare these curves. CD38 was expressed in 20% or more of leukemic cells in 43% of the patients. Patients with high CD38 expression (20% or more) had significantly shorter survival times (P =.00005). Multivariate analyses showed that CD38 expression is an important prognostic factor associated with high incidence of lymph node involvement (P = .004), lower hemoglobin level (P = .001), hepatomegaly (P = .05), and high β2M level (P = .00005). CD38 expression identified a group of patients with aggressive disease that was considered by Rai staging to be early-stage disease (Rai stages 0-II). Patients with CD38+ samples have significantly aggressive disease regardless of their clinical stage. Measurement of CD38 expression by flow cytometry should become a routine test in the evaluation of patients with CLL.
Highly abundant genes in the transcriptosome of human and baboon CD34 antigen-positive bone marrow cells
Authors: Gomes Ignatius , Sharma Tiffany T. , Mahmud Nadim , Kapp Jeffrey D. , Edassery Seby , Fulton Noreen , Liang Jie , Hoffman Ronald , Westbrook Carol A.
Published: July 2002

Nonhuman primates are useful large animal model systems for the in vivo study of hematopoietic stem cell biology. To better understand the degree of similarity of the hematopoietic systems between humans and baboons, and to explore the relevance of such studies in nonhuman primates to humans, this study was designed to compare the global gene expression profile of bone marrow CD34+ cells isolated from these 2 species. Human complementary DNA (cDNA) filter arrays containing 25 920 human cDNAs were surveyed for this purpose. The expression pattern and relative gene abundance of the 2 RNA sources were similar, with a correlation coefficient of 0.87. A total of 15 970 of these cDNAs were expressed in human CD34+ cells, of which the majority (96%) varied less than 3-fold in their relative level of expression between human and baboon. Reverse transcriptase–polymerase chain reaction analysis of selected genes confirmed that expression was comparable between the 2 species. No species-restricted transcripts have been identified, further reinforcing the high degree of similarity between the 2 populations. A subset of 1554 cDNAs, which are expressed at levels 100-fold and greater than background, is described, which includes 959 expressed sequence tags and uncharacterized cDNAs, and 595 named genes, including many that are clearly involved in hematopoiesis. The cDNAs reported here represent a selection of some of the most highly abundant genes in hematopoietic cells and provide a starting point to develop a profile of the transcriptosome of CD34+cells.
HIV-1 gp120 and chemokine activation of Pyk2 and mitogen-activated protein kinases in primary macrophages mediated by calcium-dependent, pertussis toxin–insensitive chemokine receptor signaling
Authors: Del Corno Manuela , Liu Qing-Hua , Schols Dominique , de Clercq Erik , Gessani Sandra , Freedman Bruce D. , Collman Ronald G.
Published: July 2002

Human immunodeficiency virus type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry. It was recently demonstrated that HIV-1 glycoprotein 120 (gp120) elevated calcium and activated several ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. This study shows that chemokine receptor engagement by both CCR5-dependent (R5) and CXCR4-dependent (X4) gp120 led to rapid phosphorylation of the focal adhesion-related tyrosine kinase Pyk2 in macrophages. Pyk2 phosphorylation was also induced by macrophage inflammatory protein-1β (MIP-1β) and stromal cell–derived factor-1α, chemokine ligands for CCR5 and CXCR4. Activation was blocked by EGTA and by a potent blocker of calcium release–activated Ca++(CRAC) channels, but was insensitive to pertussis toxin (PTX), implicating CRAC-mediated extracellular Ca++ influx but not Gαi protein-dependent mechanisms. Coreceptor engagement by gp120 and chemokines also activated 2 members of the mitogen-activated protein kinase (MAPK) superfamily, c-Jun amino-terminal kinase/stress-activated protein kinase and p38 MAPK. Furthermore, gp120-stimulated macrophages secreted the chemokines monocyte chemotactic protein-1 and MIP-1β in a manner that was dependent on MAPK activation. Thus, the gp120 signaling cascade in macrophages includes coreceptor binding, PTX-insensitive signal transduction, ionic signaling including Ca++ influx, and activation of Pyk2 and MAPK pathways, and leads to secretion of inflammatory mediators. HIV-1 Env signaling through these pathways may contribute to dysregulation of uninfected macrophage functions, new target cell recruitment, or modulation of macrophage infection.
Myelodysplastic syndromes, from French-American-British to World Health Organization: comparison of classifications on 431 unselected patients from a single institution
Authors: Nösslinger Thomas , Reisner Regina , Koller Elisabeth , Grüner Helga , Tüchler Heinz , Nowotny Hadwiga , Pittermann Elisabeth , Pfeilstöcker Michael
Published: July 2002

In 1999 a working group of the World Health Organization (WHO) published a revised classification for myelodysplastic syndromes (MDS): RA, RARS, refractory cytopenia with multilineage dysplasia (RC+Dys), RAEB I and II, del (5q) syndrome, and MDS unclassifiable. Chronic myelomonocytic leukemia (CMML) and RAEB-t were excluded. Standard French-American-British (FAB) and new WHO classifications have been compared in a series of patients (n = 431) from a single center, analyzing morphologic, clinical, and cytogenetic data. According to the WHO findings, dysgranulocytopoiesis or dysmegakaryocytopoiesis only were found in 26% of patients with less than 5% medullary blasts. These patients are thus unclassified and should remain in the subgroups RA and RARS. Splitting of heterogeneous RAEB into 2 subgroups according to blast count was supported by a trend to a statistically significant difference in the single-center study population. Patients with CMML whose white blood cell counts are above 13 000/μL may be excluded from the MDS classification, as warranted by WHO, but a redistribution of patients with dysplastic CMML according to medullary blast count leads to more heterogeneity in other WHO subgroups. Although the natural courses of RAEB-T and acute myeloid leukemia (AML) with dysplasia are different, comparable median survival durations after treatment in patients with RAEB-T and AML were in favor of the proposed 20% medullary blast threshold for AML. The homogeneity of subgroups was studied by evaluating prognostic scores. A significant shift into lower IPSS risk groups was evident in the new classification. These data cannot provide evidence for the new WHO proposal, which should not be adopted for routine clinical use at present. Some of its aspects can provide a starting point for further studies involving refined cytogenetics and clinical results.
Division rate and phenotypic differences discriminate alloreactive and nonalloreactive T cells transferred in lethally irradiated mice
Authors: Maury Sébastien , Salomon Benoı̂t , Klatzmann David , Cohen José L.
Published: July 2002

After non-T-cell–depleted allogeneic hematopoietic stem cell transplantation (HSCT), both alloreactive and homeostatic signals drive proliferation of donor T cells. Host-reactive donor T cells, which proliferate on alloantigen stimulation, are responsible for the life-threatening graft-versus-host disease. Non–host-reactive donor T cells, which proliferate in response to homeostatic signals, contribute to the beneficial peripheral T-cell reconstitution. The elimination of alloreactive T cells is a major therapeutic challenge for HSCT and would greatly benefit from their specific identification. After T-cell transfer in lymphopenic recipients, the present results show that alloreactive T cells rapidly divided; up-regulated CD69, CD25, and CD4 molecules; and down-regulated CD62L. In contrast, nonalloreactive T cells started to divide later and did not up-regulate CD69, CD25, and CD4. Thus, these 2 cell populations can be effectively discriminated. This should facilitate the specific depletion of alloreactive T cells in allogeneic HSCT.