bluuebunny/crossref_metadata_2025 huggingface dataset:
Clay mineralogical investigations related to nuclear waste disposal
Authors: Madsen F. T.
Published: July 2002

Mineralogical and geotechnical investigations on the possible use of compacted bentonite as a buffer material in nuclear waste repositories are reported. The swelling capacity is highly dependent on the density of the compacted bentonite. Swelling pressures >30 MPa were measured for dry densities of ~2.0 g/cm3. Added iron or magnetite powder up to 20 wt% had no influence on the swelling capacity. Compacted mixtures of 20 wt% ground set cement and bentonite showed higher swelling pressures but lower swelling strain capability than compacted bentonite alone. Steam lowered the swelling pressure of compacted bentonite to ~60% of the original value. The influence was, however, reversible by ultrasonic treatment. The thermal conductivity of saturated compacted bentonite at a density of 2.0-2.1 g/cm3is ~1.35-1.45 W/m°K The volumetric heat capacity ranges from 3.1 x 106to 3.4 x 106j/m3°C The saturated hydraulic conductivity of the compacted bentonite is <10-12m/s. The apparent diffusion coefficients for various ions in compacted bentonite for water contents in the range of 20 to 25 wt% are: K+: 5 x 10-11, Cs+: 6 x 10-12, Sr2+: 3 x 10-11, UO22+: <10-13, Th4+: <10-13, Fe2+: 4 x 10-11, Fe3+: 4 x 10-11, Cl-: 1 x 10-10and I-: 1 x 10-10m2/s. The 'breakthrough time' for an apparent diffusion coefficient of 10-11m2/s in compacted bentonite 1 m thick was estimated to be ~3000 years. The mineralogical longevity was investigated on natural K-bentonites from Kinnekulle, Sweden, and Montana, USA. Although these materials have undergone considerable changes during diagenesis and contain various amounts of mixed-layer illite-smectite, they still have a substantial swelling and adsorption capacity. The investigations demonstrate that although the properties of bentonite are negatively influenced to a certain extent by heat, hot steam, iron and cement, compacted bentonite is still the best choice to act as a buffer material in a nuclear waste repository.
New data on the kaolinite-potassium acetate complex
Authors: Ruiz Cruz M. D. , Franco Duro F. I.
Published: July 2002

The intercalation complex of kaolinite and potassium acetate (KAc) was studied by HTXRD, IR spectroscopy and DTA-TG. The HTXRD patterns indicate that the 14.06 Å basal spacing of the complex contracts to 11.77 Å and 9.35 Å after heating at 60°C. The DTA-TG data indicate that water is present in these new complexes, the decomposition of which occurs between 290°C and 400°C. Modifications observed in the high-frequency region of the spectra obtained after heating suggest that K ions occupy the ditrigonal holes in the OH surface of the kaolinite layers, whereas water is probably located between the KAc layer and the OH surface of the kaolinite. This structural arrangement would favour the H-bonding between inner-surface OH groups and water and justifies the presence of new bands at lower frequencies. Electrostatic interactions between the keyed K ions and O of the inner OH groups would justify the modifications of the 3619 cm-1 OH-stretching band.
Synthesis of troilite by the arc-discharge method
Authors: Daizhang Chen , Xiang Yang
Published: July 2002

Troilite is a sulfide that occurs commonly in meteorites. In the laboratory, it can be synthesized by gas-solid reaction of metallic Fe and H2S-H2 gas mixtures. In this research, the arc-discharge method was used to synthesize troilite. The resulting spherules are up to 2–3 mm in diameter and composed of troilite, pyrrhotite and metallic Fe. Nanometer-sized hollow carbon fibres and balls occur on the surface of the spherules. The features and coexisting relationships of the constituents of the spherules were studied by X-ray diffraction (XRD), energy-dispersive X-ray spectrometry (EDS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and the phenomenon of transformation of pyrite (FeS2) into pyrrhotite (Fe1-xS), troilite (FeS) and metallic Fe under arc-discharge reducing conditions were examined.
Arizona porphyry copper/hydrothermal deposits I. The structure of chenevixite and luetheite
Authors: Burns P. C. , Smith J. V. , Steele I. M.
Published: July 2002

The crystal structure of chenevixite, Cu2M2(AsO4)2(OH)4 (where M = Fe3+ or Al), pseudo-orthorhombic, monoclinic, a = 5.7012(8), b = 5.1801(7), c = 29.265(2) Å, β = 89.99(1)°, V = 864.3(4) Å3, space group B1211, Z = 4, was solved by direct methods and refined by least-squares techniques to R = 8.4% and a goodness-of-fit (S) of 1.37 for 1176 unique observed (F≥4σF) reflections collected for a twinned microcrystal using graphite-monochromated Mo-Kα X-rays and a CCD area detector. Vertex- and edge-sharing arsenate tetrahedra, Alϕ6 octahedra, and Jahn-Teller-distorted Cu2+ϕ6 octahedra [ϕ: O2−;, (OH)−;] form a framework unique from those in Cu2+ oxysalt minerals. Chains of edge-sharing Cu2+ϕ6 octahedra, with Alϕ6 octahedra attached on opposing sides by the sharing of edges, are linked into layers parallel to (001) by sharing vertices with AsO4 tetrahedra, and the layers are linked to form a frameworkby the sharing of polyhedral elements between adjacent Alϕ6 octahedra, as well as between AsO4 tetrahedra and Alϕ6 octahedra.
The mafic mineralogy of the Pandé massif, Tikar plain, Cameroon: implications for a peralkaline affinity and emplacement from highly evolved alkaline magma
Authors: Njonfang E. , Moreau C.
Published: July 2002

The Pandé massif is a small (4.9×63.4 km) subvolcanic complex of the Cameroon Line striking W – E and intrudes a Panafrican granite basement. It comprises a syenite-granite suite, where coarse- to finegrained syenites are predominant and the granites are the product of residual melt after syenite crystallization, and two volcanic (trachyte-rhyolite and trachyte) sequences. Amphibole and pyroxene are the dominant mafic silicates, the first occurring mainly in rhyolites and coarse- to medium-grained syenites, and the second, principally in all syenites, trachytes and granites. Rare biotite flakes are encountered in the coarse-grained or alkaline syenites and fayalite rimmed with oxides occurs in trachyte from the first volcanic sequence (T1). Apatite and zircon are common accessories, whereas some titanite occurs in the medium-grained syenites. The plutonic rocks are drusy, intrude the first volcanic sequence but pre-date the second (T2).

All the mafic minerals are Fe-rich. Detailed studies of amphibole and pyroxene show that their compositions define relatively limited trends, amphibole varying from ferro-richterite to arfvedsonite and pyroxenes along the acmite-hedenbergite join of the Ac-Hd-Di diagram, in both the intrusive suite and volcanic rocks. Where the two minerals coexist, pyroxene crystallized subsequent to amphibole, a situation generally found in late-stage or subsolidus aegirines. The overlap in plutonic and volcanic pyroxene trends suggests their crystallization from magmas of the same composition. However, the presence of quartz and fayalite in T1 and of pure aegirine in T2 and the occurrence of Zr-bearing aegirine (NaZr0.5Fe0.52+Si2O6) in the early crystallizing alkaline syenites evolving towards pure aegirine from medium- to fine-grained quartz syenites and granites, are consistent with changes in oxygen fugacities during magmatic differentiation. Two stages are distinguished: fO2 increasingly decreased from T1 to alkaline syenite emplacement (from 10−16 to 10−24 bracketed by WM and QFM buffers) where a disequilibrium, probably caused by water dissociation with volatile loss (H2) during magma degassing, favoured crystallization of Zr-bearing aegirine; a decrease in amphibole proportions towards medium-grained quartz syenites and an increase in fO2 from the medium-grained quartz syenites to granites and T2 sequence.

The Mg-poor nature of all the mafic silicates, subsolidus origin of amphiboles, crystallization of pyroxene subsequent to amphibole and subsolidus trends defined by pyroxenes are compatible with the parental magma having itself been a late-stage derivative magma, e.g. the last product of an alkaline melt from which the voluminous Mayo Darlé granite bodies crystallized.
Thermally induced transformations of Fe oxide-stabilized residues from waste incineration
Authors: Sørensen M. A. , Bender Koch C.
Published: July 2002

Air pollution control (APC) facilities at waste incinerator plants produce large quantities of solid residues rich in salts and heavy metals. Heavy metals are readily released to water from the residues and it has, therefore, been found suitable to apply a rapid co-precipitation/adsorption process as a means to immobilize the toxic elements. In the ‘Ferrox process’, this immobilization is based on co-precipitation with an Fe(III) oxide formed by oxidation of Fe(II) by air in an aqueous slurry with the APC residue at alkaline pH. In this work we have undertaken a Mössbauer spectroscopy study of the Fe oxide phase formed by precipitation at room temperature and of the oxides present after heating to 600 and 900°C. The only Fe oxide observed in the Ferrox product at room temperature is a very poorly crystalline ferrihydrite. Analytical transmission electron microscopy showed that the main elements associated with the ferrihydrite are Si and Ca. Following heating to 600°C the oxide is still characterized as an amorphous Fe oxide, and it is probable that Si associated with the ferrihydrite is decisive in preventing crystallization. After the 900°C treatment a transformation into defect maghemite is observed. Reducing gases produced from carbon in the samples probably induces this transformation. It eases, thus, the reduction of Fe(III) and the consequent formation of magnetite that eventually oxidizes to maghemite during cooling in air.
Structure and chemistry of phosphate minerals
Authors: Hawthorne Frank C.
Published: July 2002

For complex rocks in which the structure of minerals, rather than their chemical composition, changes with progressive evolution of the system, it makes sense to try and monitor such an evolving system through the progressive change in the crystal structures of the constituent phases. In effect, the paragenetic sequences of minerals in such complex environments should be related to the crystal structures of the constituent minerals. In order to consider variations in structure topology, we need to organize crystal structures into hierarchical schemes, using the hypothesis that structures may be hierarchically ordered according to the polymerization of the coordination polyhedra with higher bondstrengths. Structural units are organized according to the mode of polymerization: unconnected polyhedra, clusters, chains, sheets and frameworks.

The bond-valence structure of (OH) and (H2O) shows that on one side, (OH) and H2O are strong Lewis bases; on the other side, they are weak Lewis acids. As a result, a very important role of both (OH) and (H2O) is to prevent polymerization of the structural unit in specific directions. Thus, the dimensionality of the structural unit is controlled primarily by the amount and role of hydrogen in the structure. The way in which we have formulated these ideas also allows development of a predictive framework within which specific aspects of the chemistry and structure of phosphates can be considered.

This approach to mineral structure, applied via the idea of a structural unit, can play a major role in developing structural hierarchies in order to bring about some sort of order to the plethora of hydroxyhydrated-phosphate structures. Furthermore, by combining the idea of binary structural representation with bond-valence theory, we see the eventual possibility of predicting stoichiometry and structural characteristics of these minerals, particularly those in complex low-temperature hydrothermal environments
Textures of diffusion-controlled reaction in contact-metamorphosed Mg-rich granulite, Kokchetav area, Kazakhstan
Authors: Ashworth J. R. , Reverdatto V. V. , kolobov V. YU. , Lepetyukha V. V. , Sheplev V. S. , Bryxina N. A.
Published: July 2002

Abstrsct

In a granulite from the Kokchetav massif, a complex mineral assemblage and intricate textures have resulted from a combination of unusual rock composition and two–stage metamorphic history. The second, contact metamorphism produced mainly cordierite and anthophyllite, reflecting a bulk composition attributed to pre–metamorphic alteration of basic igneous rock. From the first, highpressure metamorphism, garnet relics persist while another mineral has been completely pseudomorphed. The garnet is partly replaced by a symplectite of three minerals: orthopyroxene vermicules in a coarser intergrowth of cordierite and calcic plagioclase. Despite variable proportions of cordierite and plagioclase, the Al:Si ratio of the symplectite is almost constant, because the proportion of orthopyroxene is smaller where the dominant aluminous mineral is cordierite (Al:Si ≈ 0.8) than where the even more aluminous plagioclase (Al:Si ≈ 0.89) is prominent. The bulk Al:Si ratio of this symplectite, approximately 0.69, is very close to that of reactant garnet (0.66), indicating that Al and Si have been retained almost completely during the local reaction, while other elements were more mobile. In the pseudomorphs, aluminous cores (with Al:Si ratios 1.61–1.93) indicate that the mineral which has been completely replaced was probably kyanite. These cores comprise plagioclase, zoisite, corundum and spinel, and are surrounded by layers of plagioclase and cordierite. Fe, Mg, and Ca have diffused to the core, through layers with low bulk concentrations of these elements, probably by grainboundary diffusion in the solid state.
Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation
Authors: Boosalis Michael S. , Bandyopadhyay Ram , Bresnick Emery H. , Pace Betty S. , Van DeMark Karyn , Zhang Baohua , Faller Douglas V. , Perrine Susan P.
Published: July 2002

Current chemotherapeutic and butyrate therapeutics that induce fetal hemoglobin expression generally also suppress erythropoiesis, limiting the production of cells containing fetal hemoglobin (F cells). Recently, selected short-chain fatty acid derivatives (SCFADs) were identified that induce endogenous γ-globin expression in K562 cells and human burst-forming units–erythroid and that increase proliferation of human erythroid progenitors and a multilineage interleukin-3–dependent hematopoietic cell line. In this report, γ-globin inducibility by these SCFADs was further demonstrated in mice transgenic for the locus control region and the entire β-globin gene locus in a yeast artificial chromosome and in 2 globin promoter-reporter assays. Conditioned media experiments strongly suggest that their proliferative activity is a direct effect of the test compounds. Investigation of potential mechanisms of action of these SCFADs demonstrates that these compounds induce prolonged expression of the growth-promoting genes c-myb andc-myc. Both butyrate and specific growth-stimulatory SCFADs induced prolonged signal transducer and activator of transcription (STAT)-5 phosphorylation and activation, and c-cisexpression, persisting for more than 120 minutes, whereas with IL-3 alone phosphorylation disappeared within minutes. In contrast to butyrate treatment, the growth-stimulating SCFADs did not result in bulk histone H4 hyperacetylation or induction of p21Waf/Cip, which mediates the suppression of cellular growth by butyrate. These findings suggest that the absence of bulk histone hyperacetylation and p21 induction, but prolonged induction of cis, myb, myc, and STAT-5 activation, contribute to the cellular proliferation induced by selected SCFADs.
Plasma elevation of stromal cell–derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells
Authors: Hattori Koichi , Heissig Beate , Tashiro Kei , Honjo Tasuku , Tateno Masatoshi , Shieh Jae-Hung , Hackett Neil R. , Quitoriano Mannix S. , Crystal Ronald G. , Rafii Shahin , Moore Malcolm A. S.
Published: July 2002

The chemokine, stromal cell–derived factor-1 (SDF1), is produced in the bone marrow and has been shown to modulate the homing of stem cells to this site by mediating chemokinesis and chemotaxis. Therefore, it was hypothesized that elevation of SDF1 level in the peripheral circulation would result in mobilization of primitive hematopoietic stem and progenitor cells. SDF1 plasma level was increased by intravenous injection of an adenoviral vector expressing SDF1α (AdSDF1) into severe combined immunodeficient mice. This resulted in a 10-fold increase in leukocyte count, a 3-fold increase in platelets, and mobilization of progenitors, including colony-forming units–granulocyte-macrophage to the peripheral circulation. In addition, AdSDF1 induced mobilization of cells with stem cell potential, including colony-forming units in spleen and long-term reconstituting cells. These data demonstrate that overexpression of SDF1 in the peripheral circulation results in the mobilization of hematopoietic cells with repopulating capacity, progenitor cells, and precursor cells. These studies lay the foundation for using SDF1 to induce mobilization of hematopoietic stem and progenitor cells in in vivo studies.
The effect of leukocyte-reduction method on the amount of human cytomegalovirus in blood products: a comparison of apheresis and filtration methods
Authors: Dumont Larry J. , Luka Janos , VandenBroeke Tania , Whitley Pamella , Ambruso Daniel R. , Elfath M. Dean
Published: July 2002

This study examined the effectiveness of 3 leukocyte-reduction (LR) methods in depleting the residual level of cytomegalovirus (CMV) in blood products measured by quantitative polymerase chain reaction (QA-PCR). At 2 locations over 3 allergy seasons, apheresis platelets and whole blood were collected from 52 healthy CMV seropositive subjects having an elevated titer of CMV DNA (median = 2400 genome equivalents [GE]/mL) resulting in 32 evaluable LR apheresis platelets, 31 filtered platelets from whole blood, and 31 filtered red blood cells (RBCs) from whole blood. Leukoreduction by apheresis and filtration resulted in substantial reduction of detectable CMV DNA levels with 99.9% of the LR products expected to have less than 500 GE/mL of CMV DNA. No difference was found between methods (P = .52). CMV genomic leukocyte subset localization was determined by QA-PCR of fluorescence-activated cell sorter (FACS)-sorted peripheral blood from 20 seropositive subjects (n = 10 > 100 GE/mL, n = 10 QA-PCR negative). CMV was detected in monocyte (13 of 20) and granulocyte (3 of 20) fractions. Presence of competent virus in QA-PCR positive (> 100 GE/mL) peripheral blood samples was verified with 4 of 19 subjects positive in shell vial assay, and 8 of 18 positive for CMV gene products (messenger RNA). We observed a seasonal DNAemia variation in seropositive subjects. CMV seropositive subjects (n = 45) entered into longitudinal monitoring in March/April 1999 were QA-PCR negative at baseline. Subjects converted to a positive QA-PCR coincident with increased seasonal allergen levels (Norfolk 15 of 18 evaluable in 43.4 ± 9.48 days; Denver, 16 of 23 evaluable in 96 ± 26.3 days). These data demonstrate effective reduction of CMV load by LR during periods of DNAemia in CMV seropositive subjects.
Signal transduction involved in MCP-1–mediated monocytic transendothelial migration
Authors: Cambien Béatrice , Pomeranz Manuel , Millet Marie-Ange , Rossi Bernard , Schmid-Alliana Annie
Published: July 2002

Monocyte chemoattractant protein-1 (MCP-1) is a major chemoattractant for monocytes and T lymphocytes. The MonoMac6 cell line was used to examine MCP-1 receptor-mediated signal transduction events in relation to MCP-1–mediated monocytic transendothelial migration. MCP-1 stimulates, with distinct time courses, extracellular signal-related kinases (ERK1 and ERK2) and stress-activated protein kinases (SAPK1/JNK1 and SAPK2/p38). SAPK1/JNK1 activation was blocked by piceatannol, indicating that it is regulated by Syk kinase, whereas SAPK2/p38 activation was inhibited by PP2, revealing an upstream regulation by Src-like kinases. In contrast, ERK activation was insensitive to PP2 and piceatannol. Pertussis toxin, a blocker of Go/Gi proteins, abrogated MCP-1–induced ERK activation, but was without any effect on SAPK1/JNK1 and SAPK2/p38 activation. These results underscore the major implication of Go/Gi proteins and nonreceptor tyrosine kinases in the early MCP-1 signaling. Furthermore, MCP-1–mediated chemotaxis and transendothelial migration were significantly diminished by a high concentration of SB202190, a broad SAPK inhibitor, or by SB203580, a specific inhibitor of SAPK2/p38, and abolished by pertussis toxin treatment. Altogether, these data suggest that coordinated action of distinct signal pathways is required to produce a full response to MCP-1 in terms of monocytic locomotion.
Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12)
Authors: Kuno Yoshie , Abe Akihiro , Emi Nobuhiko , Iida Minako , Yokozawa Toshiya , Towatari Masayuki , Tanimoto Mitsune , Saito Hidehiko
Published: July 2002

The TEL gene on 12p12-13 is a target for a number of translocations associated with various hematological malignancies. The fusion of the TEL gene to the Sykgene in a patient with myelodysplastic syndrome (MDS) with t(9;12)(q22;p12) is reported. Southern blot analysis of patient bone marrow cells with TEL and Syk gene probes detected rearranged fragments. Anchored polymerase chain reaction identified the Syk gene, a nonreceptor tyrosine kinase, on 9q22 fused downstream of TEL exon 5. The TELgene was fused in-frame to Syk and produced a fusion protein that was constitutively phosphorylated in tyrosine with dimerization that was mediated by the helix-loop-helix domain of TEL. A TEL-Syk fusion product transformed the murine hematopoietic cell line BaF3 to interleukin-3 growth factor independence. TEL-Syk is a novel transforming protein and leads to the transformation of hematopoietic cells. These data implicate that the rearranged Syk gene is involved in the pathogenesis of hematopoietic malignancies.
SH2 domain–mediated targeting, but not localization, of Syk in the plasma membrane is critical for FcεRI signaling
Authors: Sada Kiyonao , Zhang Juan , Siraganian Reuben P.
Published: July 2002

Aggregation of the high-affinity IgE receptor induces the tyrosine phosphorylation of subunits of the receptor and the subsequent association with the receptor of the cytosolic protein tyrosine kinase Syk. The current experiments examined the functional importance of membrane association of Syk and the role of the SH2 domain in receptor-mediated signal transduction. Wild-type Syk and chimeric Syk molecules with the c-Src myristylation sequence at the amino-terminus were expressed in a Syk-negative mast cell line. Chimeric Syk with the myristylation sequence was membrane associated, and a small fraction was constitutively colocalized with FcεRI, Lyn, and LAT (linker for T-cell activation) in the glycolipid-enriched microdomains or rafts. However, even under these conditions, the tyrosine phosphorylation of Syk and the downstream propagation of signals required FcεRI aggregation. This chimeric Syk was less active than wild-type Syk in FcεRI-mediated signal transduction. In contrast, a truncated membrane-associated form of Syk that lacked the SH2 domains was not tyrosine phosphorylated by receptor aggregation and failed to transduce intracellular signals. These findings suggest that SH2 domain–mediated membrane translocation of Syk is essential for the FcεRI-mediated activation of Syk for downstream signaling events leading to histamine release. Furthermore, the localization of Syk in glycolipid-enriched microdomains by itself is not enough to generate or enhance signaling events.
Growth factor–induced angiogenesis in vivo requires specific cleavage of fibrillar type I collagen
Authors: Seandel Marco , Noack-Kunnmann Katharina , Zhu Dan , Aimes Ronald T. , Quigley James P.
Published: July 2002

The contribution of specific type I collagen remodeling in angiogenesis was studied in vivo using a quantitative chick embryo assay that measures new blood vessel growth into well-defined fibrillar collagen implants. In response to a combination of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), a strong angiogenic response was observed, coincident with invasion into the collagen implants of activated fibroblasts, monocytes, heterophils, and endothelial cells. The angiogenic effect was highly dependent on matrix metalloproteinase (MMP) activity, because new vessel growth was inhibited by both a synthetic MMP inhibitor, BB3103, and a natural MMP inhibitor, TIMP-1. Multiple MMPs were detected in the angiogenic tissue including MMP-2, MMP-13, MMP-16, and a recently cloned MMP-9–like gelatinase. Using this assay system, wild-type collagen was compared to a unique collagenase-resistant collagen (r/r), with regard to the ability of the respective collagen implants to support cell invasion and angiogenesis. It was found that collagenase-resistant collagen constitutes a defective substratum for angiogenesis. In implants made with r/r collagen there was a substantial reduction in the number of endothelial cells and newly formed vessels. The presence of the r/r collagen, however, did not reduce the entry into the implants of other cell types, that is, activated fibroblasts and leukocytes. These results indicate that fibrillar collagen cleavage at collagenase-specific sites is a rate-limiting event in growth factor–stimulated angiogenesis in vivo.
Experiences of donors enrolled in a randomized study of allogeneic bone marrow or peripheral blood stem cell transplantation
Authors: Rowley Scott D. , Donaldson Gary , Lilleby Kathy , Bensinger William I. , Appelbaum Frederick R.
Published: July 2002

The experiences of 69 (38 marrow and 31 peripheral blood stem cell [PBSC]) donors participating in a randomized trial comparing allogeneic bone marrow with PBSC transplantation were studied. Marrow was collected by means of standard harvest techniques and general or regional anesthesia. PBSC donors were treated with 5 to 7 days of filgrastim at a dose of 16 μg/kg/d and underwent 1 to 3 days of apheresis to obtain 5 × 106 CD34+ cells per kilogram recipient weight. Donors completed questionnaires describing their health experiences before, during, and then weekly after donation until return to baseline status. Both marrow and PBSC donors reported minimal fluctuation in symptoms measuring emotional status. In contrast, both groups of donors reported deterioration in physical status starting with administration of filgrastim (PBSC donors) or after the marrow collection procedure. The symptom burden reported was similar, with pain a prominent symptom for both groups. Equivalent mean levels of maximal pain, average pain, and pain duration through the day were reported, although toxicity peaks occurred at different time points during the harvest procedures. All PBSC donors but only 79% of marrow donors reported good physical status by 14 days after the harvest procedures. These data demonstrate similar levels of physical discomfort for hematopoietic stem cell donors regardless of the collection procedure used, but a quicker resolution of symptoms for PBSC donors.
Diagnostic and clinical relevance of the number of circulating CD34+ cells in myelofibrosis with myeloid metaplasia
Authors: Barosi Giovanni , Viarengo Gianluca , Pecci Alessandro , Rosti Vittorio , Piaggio Giovanna , Marchetti Monia , Frassoni Francesco
Published: July 2002

The absolute content of CD34+ cells in the peripheral blood of 84 patients with myelofibrosis with myeloid metaplasia (MMM) and 23 patients with other Philadelphia-negative (Ph−) chronic myeloproliferative disorders (CMDs) was investigated. In MMM, the median absolute number of circulating CD34+cells was consistently high (91.6 × 106/L; range, 0-2460 × 106/L). Receiver operating characteristic curve analysis showed that 15 × 106/L as a decision criterion for CD34+cells produced an almost complete discrimination between MMM patients out of therapy and other Ph− CMDs (positive predictive value, 98.4%; negative predictive value, 85.0%). MMM patients with higher numbers of CD34+ cells had a significantly longer disease duration (P = .019) and higher spleen volume index (P = .014), liver volume (P = .000), percentage of circulating immature myeloid cells (P = .020), and percentage of myeloid blasts (P = .000). When CD34+ cells were correlated with the use of Dupriez risk stratification, CD34+ cells increased significantly from low-risk (median, 68.1 × 106/L) to intermediate-risk (median, 112.8 × 106/L) and high-risk patients (median 666.1 × 106/L) (F = 4.95;P = .009). When CD34+ cells were correlated with a severity score on the basis of both myeloproliferative and myelodepletive characteristics of the disease, only the myeloproliferation index was significantly associated with CD34+ cell level (F = 5.7;P = .000). Overall survival and interval to blast transformation from the time of CD34+ cell analysis were significantly shorter in patients with more than 300 × 106/L CD34+ cells (P = .005 and .0005, respectively). In conclusion, the absolute number of CD34+ circulating cells allows MMM to be distinguished from other Ph− CMDs; it is strongly associated with the extent of myeloproliferation and predicts evolution toward blast transformation.
A proteolytically truncated form of free CD18, the common chain of leukocyte integrins, as a novel marker of activated myeloid cells
Authors: Drbal Karel , Angelisová Pavla , Hilgert Ivan , Černý Jan , Novák Petr , Hořejšı́ Václav
Published: July 2002

An unusual CD18 monoclonal antibody (mAb) MEM-148 binds, in contrast to standard CD18 mAbs, specifically to peripheral blood monocytes and neutrophils activated by various stimuli such as phorbol myristate acetate, opsonized zymosan, heat-aggregated immunoglobulin, and (after priming with lipopolysaccharide, tumor necrosis factor, or granulocyte-macrophage colony-stimulating factor) also by formyl-methionyl-leucyl-phenylalanine. In addition, in vivo activated neutrophils obtained from urine of patients following recent prostatectomy were also strongly positive for MEM-148. On the activated myeloid cells the mAb recognized a 65- to 70-kd protein identified immunochemically and by mass spectrometric peptide sequencing as a membrane-anchored fragment of CD18 (the common chain of leukocyte integrins) produced by proteolytic cleavage. The CD18 fragment originated mainly from integrin molecules stored intracellularly in resting cells, it was unassociated with CD11 chains, and its formation was inhibited by several types of protease inhibitors. Thus, the 65- to 70-kd CD18 fragment represents a novel abundant activation marker of myeloid cells of so far unknown function but possibly involved in conformational changes in leukocyte integrin molecules resulting in increased affinity to their ligands.
Vγ2Vδ2 T-cell receptor–mediated recognition of aminobisphosphonates
Authors: Das Hiranmoy , Wang Lisheng , Kamath Arati , Bukowski Jack F.
Published: July 2002

Aminobisphosphonates, potent derivatives of bisphosphonates, are frequently used for the treatment of conditions such as osteoporosis and bone metastases that are characterized by excessive osteoclastic bone resorption. Using T-cell receptor (TCR) transfer studies, we show that recognition of antigenic aminobisphosphonates that are known to stimulate human γδ T cells in vitro and in vivo (potency: risedronate > alendronate > pamidronate) requires expression of the Vγ2Vδ2 TCR and is thus Vγ2Vδ2 TCR–dependent. Myeloma cells or monocytes pulsed with risedronate and then washed rendered these target cells sensitive to lysis by a Vγ2Vδ2 T-cell clone or cell line. These results suggest that Vγ2Vδ2 TCR–dependent recognition leading to direct cytolysis of aminobisphosphonate-sensitized osteoclast or tumor targets may be a mechanism whereby aminobisphosphonate treatment of cancers metastatic to bone decreases osteoclastic activity and tumor burden and also may account for the decreased osteoclastic activity associated with successful treatment of osteoporosis.
Delayed donor red cell chimerism and pure red cell aplasia following major ABO-incompatible nonmyeloablative hematopoietic stem cell transplantation
Authors: Bolan Charles D. , Leitman Susan F. , Griffith Linda M. , Wesley Robert A. , Procter Jo L. , Stroncek David F. , Barrett A. John , Childs Richard W.
Published: July 2002

Delayed donor red cell engraftment and pure red cell aplasia (PRCA) are well-recognized complications of major ABO-incompatible hematopoietic stem cell transplantation (SCT) performed by means of myeloablative conditioning. To evaluate these events following reduced-intensity nonmyeloablative SCT (NST), consecutive series of patients with major ABO incompatibility undergoing either NST (fludarabine/cyclophosphamide conditioning) or myeloablative SCT (cyclophosphamide/high-dose total body irradiation) were compared. Donor red blood cell (RBC) chimerism (initial detection of donor RBCs in peripheral blood) was markedly delayed following NST versus myeloablative SCT (median, 114 versus 40 days;P < .0001) and strongly correlated with decreasing host antidonor isohemagglutinin levels. Antidonor isohemagglutinins declined to clinically insignificant levels more slowly following NST than myeloablative SCT (median, 83 versus 44 days;P = .03). Donor RBC chimerism was delayed more than 100 days in 9 of 14 (64%) and PRCA occurred in 4 of 14 (29%) patients following NST, while neither event occurred in 12 patients following myeloablative SCT. Conversion to full donor myeloid chimerism following NST occurred significantly sooner in cases with, compared with cases without, PRCA (30 versus 98 days; P = .008). Cyclosporine withdrawal appeared to induce graft-mediated immune effects against recipient isohemagglutinin-producing cells, resulting in decreased antidonor isohemagglutinin levels and resolution of PRCA following NST. These data indicate that significantly delayed donor erythropoiesis is (1) common following major ABO-incompatible NST and (2) associated with prolonged persistence of host antidonor isohemagglutinins. The clinical manifestations of these events are affected by the degree and duration of residual host hematopoiesis.
Relationship between transferrin saturation and iron stores in the African American and US Caucasian populations: analysis of data from the third National Health and Nutrition Examination Survey
Authors: McLaren Christine E. , Li Kuo-Tung , Gordeuk Victor R. , Hasselblad Victor , McLaren Gordon D.
Published: July 2002

In previous analyses of transferrin saturation data in African Americans and Caucasians from the second National Health and Nutrition Examination Survey (NHANES II), subpopulations were found consistent with population genetics for common loci that influence iron metabolism. The goal of this new study was to determine if these transferrin saturation subpopulations have different levels of iron stores. Statistical mixture modeling was applied to transferrin saturation data for African Americans and Caucasians from the third National Health and Nutrition Examination Survey (NHANES III), and then the mean serum ferritin concentrations were determined for the transferrin saturation subpopulations that were identified. After adjustment for diurnal variation, 3 subpopulations of transferrin saturation were identified in each racial group. Satisfying Hardy-Weinberg conditions for major locus effects, in both racial groups the sum of the square roots of the proportion with the lowest mean transferrin saturation and the proportion with the highest mean transferrin saturation was approximately 1. When weighted to reflect the US adult population as a whole, these subpopulations of increasing transferrin saturations had progressively increasing mean age-adjusted serum ferritin concentration values in each ethnic grouping as stratified by sex (trend test, P < .002 for all). These results are consistent with the concept that population transferrin saturation subpopulations reflect different levels of storage iron.
Loss of blood CD11c+ myeloid and CD11c−plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load
Authors: Donaghy Heather , Pozniak Anton , Gazzard Brian , Qazi Nad , Gilmour Jill , Gotch Frances , Patterson Steven
Published: July 2002

Human blood contains at least 2 subpopulations of antigen-presenting dendritic cells (DCs) that can be differentiated by their expression of CD11c. Myeloid DCs (myDCs), which are CD11c+, trap invading pathogens in the tissues and then migrate to lymphoid tissues where they stimulate pathogen-specific T-cell responses. Plasmacytoid DCs (pcDCs), which are CD11c−, secrete interferon-α in response to viral infections. This study reports that in HIV-1 infection there is a progressive depletion of both these DC populations and that this correlates with an increasing HIV-1 plasma virus load. The median numbers of myDCs and pcDCs were 6978/mL and 9299/mL, respectively, in healthy male controls and 2298/mL and 1640/mL, respectively, in patients with more than 105 HIV-1 RNA copies/mL. Both DC populations expressed CD4, CCR5, and CXCR4. The findings suggest that loss of DCs in HIV infection may contribute to disease progression.
Sphingosine 1-phosphate antagonizes apoptosis of human leukemia cells by inhibiting release of cytochrome c and Smac/DIABLO from mitochondria
Authors: Cuvillier Olivier , Levade Thierry
Published: July 2002

Sphingosine 1-phosphate (S-1P) has been implicated as a second messenger preventing apoptosis by counteracting activation of executioner caspases. Here it is reported that S-1P prevents apoptosis and executioner caspase-3 activation by inhibiting the translocation of cytochrome c and Smac/DIABLO from mitochondria to the cytosol induced by anti-Fas, tumor necrosis factor-α (TNF-α), serum deprivation, and cell-permeable ceramides in the human acute leukemia Jurkat, U937, and HL-60 cell lines. Furthermore, the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate, which stimulates sphingosine kinase, the enzyme responsible for S-1P production, also inhibits cytochrome c and Smac/DIABLO release. In contrast, dimethylsphingosine (DMS), a specific inhibitor of sphingosine kinase, sensitizes cells to cytochrome c and Smac/DIABLO release triggered by anti-Fas, TNF-α, serum deprivation, or ceramide. DMS-induced mitochondrial apoptogenic factor leakage can likewise be overcome by S-1P cotreatment. Hence, S-1P, likely generated through a protein kinase C– mediated activation of sphingosine kinase, inhibits the apoptotic cascade upstream of the release of the mitochondrial apoptogenic factors, cytochrome c, and Smac/DIABLO in human acute leukemia cells.
Acidic and neutral sialidase in the erythrocyte membrane of type 2 diabetic patients
Authors: Venerando Bruno , Fiorilli Amelia , Croci Gianluigi , Tringali Cristina , Goi Giancarlo , Mazzanti Laura , Curatola Giovanna , Segalini Giovanni , Massaccesi Luca , Lombardo Adriana , Tettamanti Guido
Published: July 2002

The behavior of the 2 sialidase forms present in the erythrocyte membrane was investigated in 117 subjects with type 2 diabetes mellitus versus 95 healthy controls. A significant increase of the acidic form of sialidase, which is anchored to the membrane by a glycosylphosphatidylinositol bridge, was observed in erythrocyte resealed membranes. On the contrary, the neutral form of the enzyme, the only one capable of removing lipid- and protein-bound sialic acid from endogenous and exogenous sialoderivatives, was significantly reduced with a consequent increase of erythrocyte membrane total sialic acid content. Disease duration, therapy, glycemia, parameters of metabolic control, and presence of complications, except nephropathies, had no influence on the tested enzyme activities. Diabetic subjects showed a different erythrocyte age distribution, with an almost double proportion of young red cells and only one quarter of senescent ones compared with controls. In young erythrocytes, diabetic and control subjects had the same distribution of the 2 enzymes, while in senescent cells the acidic enzyme was increased 3.5-fold and the neutral form was reduced by half in the diabetic subjects. The increase of both acidic sialidase and total membrane-bound sialic acid, together with an overpresence of young red cells in diabetics, suggests that in this pathological condition there might be an altered aging process with a diminished expression of the neutral form of the enzyme and an increase of bound sialic acid. It has been suggested that the expression of the neutral enzyme requires some activation mechanism that is impaired in diabetes.
Partial deletion in the JK locus causing a Jknull phenotype
Authors: Lucien Nicole , Chiaroni Jacques , Cartron Jean-Pierre , Bailly Pascal
Published: July 2002

A new alteration of the blood group JK*A allele was identified in a Jknull patient from Tunisia with an allo–anti-Jk3 in her serum. Southern blot and exon mapping analyses revealed an internal deletion within the Kidd (JK) locus encompassing exons 4 and 5. Sequence analysis of the Jk transcript showed that exons 4 and 5 were missing but were replaced by a 136–base-pair (bp) intron 3 sequence located 315 bp and 179 bp upstream from exon 4. This sequence is flanked by typical donor–acceptor cryptic splice sites used in the mutant but not in the normal JK gene. Because the translation initiation codon is located in exon 4, the Jk protein is not produced.
Lineage-specific defect in gene expression in human platelet phospholipase C-β2 deficiency
Authors: Mao Guang Fen , Vaidyula Vijender R. , Kunapuli Satya P. , Rao A. Koneti
Published: July 2002

Phospholipase C (PLC)–β2 plays a major role in platelet activation. Previous studies have described a unique patient with impaired receptor-mediated platelet aggregation, secretion, calcium mobilization, and phospholipase C (PLC) activation associated with a selective decrease in platelet PLC-β2 isozyme. To identify the mechanisms leading to the defect, platelet RNA from the patient and healthy subjects was subjected to reverse transcription–polymerase chain reaction (RT-PCR) and the products sequenced. The PLC-β2 cDNA sequence in the patient showed no abnormalities. Platelet PLC-β2 and β-actin (internal control) mRNA levels were assessed by RT-PCR; the ratio of PLC-β2 to β-actin mRNA levels was 0.80 to 0.95 in 4 healthy subjects and 0.28 in the patient. PLC-β2 mRNA levels were similarly reduced compared with GPIIb and Gαq mRNA levels. PLC-γ2 and platelet factor 4 mRNA levels were normal. Calcium mobilization was studied in neutrophils upon activation with formyl-Met-Leu-Phe (fMLP), adenosine diphosphate (ADP), platelet-activating factor (PAF), interleukin-8 (IL-8), C5a, and leukotriene B4 (LTB4), and it was normal. Neutrophil elastase secretion upon activation with fMLP, ADP, PAF, IL-8, C5a, and LTB4 was normal, as were neutrophil PLC-β2 mRNA and PLC-β2 on immunoblotting. Thus, responses to activation, PLC-β2 protein, and PLC-β2 mRNA are decreased in patient platelets but not in neutrophils, providing evidence for a hitherto undescribed lineage (platelet)–specific defect in PLC-β2 gene expression. These studies provide a physiologically relevant model to delineate regulation of PLC-β2 gene and its tissue-specific expression.
A functional platelet fibrinogen receptor with a deletion in the cysteine-rich repeat region of the β3 integrin: the Oea alloantigen in neonatal alloimmune thrombocytopenia
Authors: Santoso Sentot , Kiefel Volker , Richter Ina G. , Sachs Ulrich J. H. , Rahman Abdul , Carl Bettina , Kroll Harmut
Published: July 2002

This report describes a new low-frequency alloantigen, Oea, responsible for a case of neonatal alloimmune thrombocytopenia (NAIT). In a population study none of 600 unrelated blood donors was an Oea carrier. By immunochemical studies the Oea antigen could be assigned to platelet glycoprotein (GP) IIIa. Sequencing of GPIIIa complementary DNA from an Oea (+) individual showed deletion of a lysine residue at position 611 (ΔLys611). Analysis of 20 Oea(−) and 3 Oea (+) individuals showed that the ΔLys611 form of GPIIIa was related to the phenotype. Anti-Oea reacted with the ΔLys611, but not with the wild-type isoforms on stable transfectants expressing GPIIIa, indicating that ΔLys611 directly induces the expression of Oea epitopes. Under nonreducing conditions the Pro33ΔLys611 variant migrated with a slightly decreased molecular weight compared to the Pro33Lys611 isoform suggesting that ΔLys611 has an influence on the disulfide bonds of GPIIIa. The Pro33ΔLys611 GPIIIa could undergo conformational changes and bind to fibrinogen in a similar manner as the Pro33Lys611 isoform. No difference was found in the tyrosine phosphorylation of pp125FAK, suggesting that ΔLys611 has no effect on integrin function. In contrast to all other low-frequency antigens, the ΔLys611 isoform was associated with the HPA-1b, but not with the high frequency HPA-1a allele. Comparison with GPIIIa DNA from nonhuman primates indicated that the HPA-1a allele represents the ancestral form of GPIIIa. It can be assumed that the Oea form did arise as a result of a mutational event from an already mutated GPIIIa allele.
Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1–transformed T cells
Authors: Yoshie Osamu , Fujisawa Ryuichi , Nakayama Takashi , Harasawa Hitomi , Tago Hideaki , Izawa Dai , Hieshima Kunio , Tatsumi Youichi , Matsushima Kouji , Hasegawa Hitoshi , Kanamaru Akihisa , Kamihira Shimeru , Yamada Yasuaki
Published: July 2002

Chemokines and chemokine receptors play important roles in migration and tissue localization of various lymphocyte subsets. Here, we report the highly frequent expression of CCR4 in adult T-cell leukemia (ATL) and human T-cell leukemia virus type 1 (HTLV-1)–immortalized T cells. Flow cytometric analysis revealed that ATL and HTLV-1–immortalized T-cell lines consistently expressed CCR4. Inducible expression of HTLV-1 transcriptional activator tax in a human T-cell line Jurkat did not, however, up-regulate CCR4 mRNA. In vitro immortalization of peripheral blood T cells led to preferential outgrowth of CD4+ T cells expressing CCR4. We further demonstrated highly frequent expression of CCR4 in fresh ATL cells by (1) reverse transcriptase–polymerase chain reaction (RT-PCR) analysis of CCR4 expression in peripheral blood mononuclear cells (PBMCs) from patients with ATL and healthy controls; (2) flow cytometric analysis of CCR4-expressing cells in PBMCs from patients with ATL and healthy controls; (3) CCR4 staining of routine blood smears from patients with ATL; and (4) an efficient migration of fresh ATL cells to the CCR4 ligands, TARC/CCL17 and MDC/CCL22, in chemotaxis assays. Furthermore, we detected strong signals for CCR4, TARC, and MDC in ATL skin lesions by RT-PCR. Collectively, most ATL cases have apparently derived from CD4+ T cells expressing CCR4. It is now known that circulating CCR4+ T cells are mostly polarized to Th2 and also contain essentially all skin-seeking memory T cells. Thus, HTLV-1–infected CCR4+ T cells may have growth advantages by deviating host immune responses to Th2. CCR4 expression may also account for frequent infiltration of ATL into tissues such as skin and lymph nodes.