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Mechanical strength of the titin Z1Z2-telethonin complex. | Using molecular dynamics simulations; we have explored the mechanical strength of the titin Z1Z2-telethonin complex; namely; its ability to bear strong forces such as those encountered during passive muscle stretch. Our results show that not only does this complex resist considerable mechanical force through beta strand crosslinking; suggesting that telethonin is an important component of the N-terminal titin anchor; but also that telethonin distributes these forces between its two joined titin Z2 domains t | 16531234 | [
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Mechanical strength of the titin Z1Z2-telethonin complex. | o protect the proximal Z1 domains from bearing too much stress. Our simulations also reveal that without telethonin; apo-titin Z1Z2 exhibits significantly decreased resistance to mechanical stress; and that the N-terminal segment of telethonin (residues 1-89) does not exhibit a stable fold conformation when it is unbound from titin Z1Z2. Consequently; our study sheds light on a key but little studied architectural feature of biological cells-the existence of strong mechanical links that glue separate protei | 16531234 | [
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Structural basis of RNA binding discrimination between bacteriophages Qbeta and MS2. | Sequence-specific interactions between RNA stem-loops and coat protein (CP) subunits play vital roles in the life cycles of the RNA bacteriophages; e.g.; by allowing translational repression of their replicase cistrons and tagging their own RNA genomes for encapsidation. The CPs of bacteriophages Qbeta and MS2 each discriminate in favor of their cognate translational operators; even in the presence of closely related operators from other phages in vivo. Discrete mutations within the MS2 CP have been shown t | 16531233 | [
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Structural basis of RNA binding discrimination between bacteriophages Qbeta and MS2. | o relax this discrimination in vitro. We have determined the structures of eight complexes between such mutants and both MS2 and Qbeta stem-loops with X-ray crystallography. In conjunction with previously determined in vivo repression data; the structures enable us to propose the molecular basis for the discrimination mechanism. | 16531233 | [
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Cryo-electron microscopy studies of human TFIID: conformational breathing in the integration of gene regulatory cues. | The multisubunit transcription factor TFIID is essential for directing eukaryotic promoter recognition and mediating interactions with activators/cofactors during assembly of the preinitiation complex. Despite its central role in transcription initiation and regulation; structural knowledge of the TFIID complex has so far been largely limited to electron microscopy studies of negatively stained samples. Here; we present a cryo-electron microscopy 3D reconstruction of the large endogenous human TFIID complex | 16531235 | [
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Cryo-electron microscopy studies of human TFIID: conformational breathing in the integration of gene regulatory cues. | . The improved cryopreservation has allowed for a more detailed definition of the structural elements in the complex and for the detection; by an extensive statistical analysis of the data; of a conformational opening and closing of the cavity central to the TFIID architecture. We propose that these density rearrangements in the structure are a likely reflection of the plasticity of the interactions between TFIID and its many partner proteins. | 16531235 | [
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Unfolding barriers in bacteriorhodopsin probed from the cytoplasmic and the extracellular side by AFM. | Selecting an individual membrane protein and probing its mechanical properties has become possible by AFM-based single-molecule force spectroscopy. In contrast to earlier studies; we extracted and unfolded bacteriorhodopsin monomers from the purple membrane not only from the cytoplasmic side; but also from the extracellular side; and recorded the force extension profiles. This way different pathways through the potential landscape are explored. A map of the 21 most dominant barriers with their positions rel | 16531236 | [
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Unfolding barriers in bacteriorhodopsin probed from the cytoplasmic and the extracellular side by AFM. | ative to the amino acid sequences is given at an accuracy of +/-3 aa. Most barriers were found to provide resistance to forced unfolding only when extracted toward one of the sides. However; certain barriers have identical positions to within a few amino acids when probed from either of the sides; which typifies them as structural traps. | 16531236 | [
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Conformational and sequence signatures in beta helix proteins. | beta helix proteins are characterized by a repetitive fold; in which the repeating unit is a beta-helical coil formed by three strand segments linked by three loop segments. Using a data set of left- and right-handed beta helix proteins; we have examined conformational features at equivalent positions in successive coils. This has provided insights into the conformational rules that the proteins employ to fold into beta helices. Left-handed beta helices attain their equilateral prism fold by incorporating " | 16531237 | [
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Conformational and sequence signatures in beta helix proteins. | corners" with the conformational sequence P(II)-P(II)-alpha(L)-P(II); which imposes sequence restrictions; resulting in the first and third P(II) residues often being G and a small; uncharged residue (V; A; S; T; C); respectively. Right-handed beta helices feature mid-sized loops (4; 5; or 6 residues) of conserved conformation; but not of conserved sequence; they also display an alpha-helical residue at the C-terminal end of L2 loops. Backbone conformational parameters (phi;psi) that permit the formation of | 16531237 | [
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Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex. | Interactions between the WW domains of Drosophila Nedd4 (dNedd4) and Commissureless (Comm) PY motifs promote axon crossing at the CNS midline and muscle synaptogenesis. Here we report the solution structure of the dNedd4 WW3* domain complexed to the second PY motif (227'TGLPSYDEALH237') of Comm. Unexpectedly; there are interactions between WW3* and ligand residues both N- and C-terminal to the PY motif. Residues Y232'-L236' form a helical turn; following the PPII helical PY motif. Mutagenesis and binding st | 16531238 | [
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Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex. | udies confirm the importance of these extensive contacts; not simultaneously observed in other WW domain complexes; and identify a variable loop in WW3* responsible for its high-affinity interaction. These studies expand our general understanding of the molecular determinants involved in WW domain-ligand recognition. In addition; they provide insights into the specific regulation of dNedd4-mediated ubiquitination of Comm and subsequent internalization of Comm or the Comm/Roundabout complex; critical for CNS | 16531238 | [
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] |
Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex. | and muscle development. | 16531238 | [
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Principles of protein-DNA recognition revealed in the structural analysis of Ndt80-MSE DNA complexes. | The Saccharomyces cerevisiae transcription factor Ndt80 selectively binds a DNA consensus sequence (the middle sporulation element [MSE]) to activate gene expression after the successful completion of meiotic recombination. Here we report the X-ray crystal structures of Ndt80 bound to ten distinct MSE variants. Comparison of these structures with the structure of Ndt80 bound to a consensus MSE reveals structural principles that determine the DNA binding specificity of this transcription factor. The 5' GC-ri | 16531239 | [
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Principles of protein-DNA recognition revealed in the structural analysis of Ndt80-MSE DNA complexes. | ch end of the MSE contains distinct 5'-YpG-3' steps that are recognized by arginine side chains through a combination of hydrogen bonding and cation-pi interactions. The 3' AT-rich region is recognized via minor groove contacts that sterically exclude the N2 atom of GC base pairs. The conformation of the AT-rich region is fixed by interactions with the protein that favor recognition of poly(A)-poly(T) versus mixed AT sequences through an avoidance of major groove steric clashes at 5'-ApT-3' steps. | 16531239 | [
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Structure-guided engineering of xylitol dehydrogenase cosubstrate specificity. | Xylitol dehydrogenase (XDH) is one of several enzymes responsible for assimilating xylose into eukaryotic metabolism and is useful for fermentation of xylose contained in agricultural byproducts to produce ethanol. For efficient xylose utilization at high flux rates; cosubstrates should be recycled between the NAD+-specific XDH and the NADPH-preferring xylose reductase; another enzyme in the pathway. To understand and alter the cosubstrate specificity of XDH; we determined the crystal structure of the Gluco | 16531240 | [
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Structure-guided engineering of xylitol dehydrogenase cosubstrate specificity. | nobacter oxydans holoenzyme to 1.9 angstroms resolution. The structure reveals that NAD+ specificity is largely conferred by Asp38; which interacts with the hydroxyls of the adenosine ribose. Met39 stacked under the purine ring and was also located near the 2' hydroxyl. Based on the location of these residues and on sequence alignments with related enzymes of various cosubstrate specificities; we constructed a double mutant (D38S/M39R) that was able to exclusively use NADP+; with no loss of activity. | 16531240 | [
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Conformational flexibility in the multidrug efflux system protein AcrA. | Intrinsic resistance to multiple drugs in many gram-negative bacterial pathogens is conferred by resistance nodulation cell division efflux pumps; which are composed of three essential components as typified by the extensively characterized Escherichia coli AcrA-AcrB-TolC system. The inner membrane drug:proton antiporter AcrB and the outer membrane channel TolC export chemically diverse compounds out of the bacterial cell; and require the activity of the third component; the periplasmic protein AcrA. The cr | 16531241 | [
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Conformational flexibility in the multidrug efflux system protein AcrA. | ystal structures of AcrB and TolC have previously been determined; and we complete the molecular picture of the efflux system by presenting the structure of a stable fragment of AcrA. The AcrA fragment resembles the elongated sickle shape of its homolog Pseudomonas aeruginosa MexA; being composed of three domains: beta-barrel; lipoyl; and alpha-helical hairpin. Notably; unsuspected conformational flexibility in the alpha-helical hairpin domain of AcrA is observed; which has potential mechanistic significanc | 16531241 | [
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Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil. | Rho-kinase is a key regulator of cytoskeletal events and a promising drug target in the treatment of vascular diseases and neurological disorders. Unlike other protein kinases; Rho-kinase requires both N- and C-terminal extension segments outside the kinase domain for activity; although the details of this requirement have been elusive. The crystal structure of an active Rho-kinase fragment containing the kinase domain and both the extensions revealed a head-to-head homodimer through the N-terminal extensio | 16531242 | [
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] |
Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil. | n forming a helix bundle that structurally integrates the C-terminal extension. This structural organization enables binding of the C-terminal hydrophobic motif to the N-terminal lobe; which defines the correct disposition of helix alphaC that is important for the catalytic activity. The bound inhibitor fasudil significantly alters the conformation and; consequently; the mode of interaction with the catalytic cleft that contains local structural changes. Thus; both kinase and drug conformational pliability | 16531242 | [
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Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil. | and stability confer selectivity. | 16531242 | [
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Serendipitous discovery and X-ray structure of a human phosphate binding apolipoprotein. | We report the serendipitous discovery of a human plasma phosphate binding protein (HPBP). This 38 kDa protein is copurified with the enzyme paraoxonase. Its X-ray structure is similar to the prokaryotic phosphate solute binding proteins (SBPs) associated with ATP binding cassette transmembrane transporters; though phosphate-SBPs have never been characterized or predicted from nucleic acid databases in eukaryotes. However; HPBP belongs to the family of ubiquitous eukaryotic proteins named DING; meaning that | 16531243 | [
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Serendipitous discovery and X-ray structure of a human phosphate binding apolipoprotein. | phosphate-SBPs are also widespread in eukaryotes. The systematic absence of complete genes for eukaryotic phosphate-SBP from databases is intriguing; but the astonishing 90% sequence conservation between genes belonging to evolutionary distant species suggests that the corresponding proteins play an important function. HPBP is the only known transporter capable of binding phosphate ions in human plasma and may become a new predictor of or a potential therapeutic agent for phosphate-related diseases such as | 16531243 | [
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Serendipitous discovery and X-ray structure of a human phosphate binding apolipoprotein. | atherosclerosis. | 16531243 | [
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Novel homeobox gene recombination in T-cell acute lymphoblastic leukemia. | nan | 16531247 | [
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Cytotoxicity of Campath-1H for acute lymphoblastic leukemia cells carrying the t(12;21) translocation. | nan | 16531248 | [
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The role of graft-versus-host disease in the inhibition of normal B-lymphopoiesis and leukemic control of B-lineage acute lymphocytic leukemia after allogeneic stem cell transplantation. | nan | 16531250 | [
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Biclonality versus intraclonal evolution of a single tumor cell clone in B-cell chronic lymphoproliferative disorders. | nan | 16531249 | [
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Is this clinical trial fully registered? A statement from the International Committee of Medical Journal Editors. | nan | 16531251 | [
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Registration of clinical trials: a step forward but still a long path ahead. | nan | 16531252 | [
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The biological characteristics of CD34+ CD2+ adult acute promyelocytic leukemia and the CD34 CD2 hypergranular (M3) and microgranular (M3v) phenotypes. | Acute promyelocytic leukemia (APL) is characterized by leukemic cells blocked at the promyelocytic stage of granulocytic differentiation. To date; it is still not clear whether CD34 expression identifies a subset of APL patients with peculiar characteristics. We; therefore; conducted a detailed analysis of CD34 expression at diagnosis in 136 adults with de novo APL.We investigated 136 newly diagnosed APL patients from four Italian Institutions. All 136 cases were tested for CD34 and CD2 expression: 124 (91% | 16531253 | [
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The biological characteristics of CD34+ CD2+ adult acute promyelocytic leukemia and the CD34 CD2 hypergranular (M3) and microgranular (M3v) phenotypes. | ) cases were classified as hypergranular (M3) and 12 (9%) as the hyporgranular M3 variant (M3v). The parameters considered were white blood cell (WBC) and platelet counts; hemoglobin levels; percentage of peripheral blood leukemic promyelocytes (PBLP); CD15; CD56 and HLA-DR expression; and the PML/RARalpha isoform; to assess their relationship with CD34 and CD2 expression.CD34 expression was associated with the M3v subtype and higher proportion of HLA-DR+ and CD2+ cases. Moreover; compared with CD34- APL pa | 16531253 | [
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The biological characteristics of CD34+ CD2+ adult acute promyelocytic leukemia and the CD34 CD2 hypergranular (M3) and microgranular (M3v) phenotypes. | tients; CD34+ APL patients had a significantly higher percentage of PBLP at presentation; were more frequently female and had a higher proportion of bcr3 expression. Among the 136 APL cases; 24 (17.6%) and 80 (58.8%) were identified as CD34+CD2+ and CD34-CD2-; respectively. The two groups showed statistically significant differences in terms of M3vfrequency; WBC and platelet counts; percentage of PBLP; and bcr3 expression. Moreover; the CD34+CD2+ group showed a higher proportion of CD34+ and bcr3 isoforms c | 16531253 | [
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The biological characteristics of CD34+ CD2+ adult acute promyelocytic leukemia and the CD34 CD2 hypergranular (M3) and microgranular (M3v) phenotypes. | ompared to the M3v cases. There were no differences between the two groups in terms of complete remission; overall survival and disease-free survival.Our findings suggest that immunophenotypic analysis can distinguish a subset of APL patients with different biological characteristics. | 16531253 | [
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The effect of a novel recombination between the homeobox gene NKX2-5 and the TRD locus in T-cell acute lymphoblastic leukemia on activation of the NKX2-5 gene. | The NK-like homeobox gene (NKX2-5/CSX) plays a crucial role in cardiac development but is not normally expressed in hematopoietic cells. Here; we describe for the first time a fusion between NKX2-5 and the T-cell receptor delta locus (TRD) resulting in NKX2-5 activation in a case of T-cell acute lymphoblastic leukemia (T-ALL).Genomic DNA from a T-ALL patient with an atypical rearrangement; detected by Southern blotting; was analyzed by ligation-mediated polymerase chain reaction (PCR) with TRD-specific prim | 16531254 | [
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The effect of a novel recombination between the homeobox gene NKX2-5 and the TRD locus in T-cell acute lymphoblastic leukemia on activation of the NKX2-5 gene. | ers. Expression of NKX2-5 was analyzed by real-time quantitative PCR in the T-ALL case with the NKX2-5-TRD rearrangement; 18 other cases of T-ALL; three T-ALL derived cell lines; two non-hematopoietic cell lines; peripheral blood mononuclear cells from six healthy individuals and sorted thymocyte subsets.Sequence analysis of ligation-mediated PCR products revealed a novel rearrangement between the third diversity segment of the TRD locus (TRDD3) and a region on chromosome 5q35.1 located 32 kb downstream of | 16531254 | [
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The effect of a novel recombination between the homeobox gene NKX2-5 and the TRD locus in T-cell acute lymphoblastic leukemia on activation of the NKX2-5 gene. | the NKX2-5/CSX gene. As a result of this recombination NKX2-5 was placed under influence of the TRD enhancer; resulting in strong ectopic NKX2-5 expression. High NKX2-5 expression was also found in the T-cell lines PEER and CCRF-CEM; which harbor an NKX2-5-BCL11B rearrangement; and in the embryonic kidney cell line 293. NKX2-5 was not expressed in any of the major thymocyte subsets; in normal peripheral blood mononuclear cells; or in the majority (17/18) of the other cases of T-ALL.Our finding of overexpres | 16531254 | [
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The effect of a novel recombination between the homeobox gene NKX2-5 and the TRD locus in T-cell acute lymphoblastic leukemia on activation of the NKX2-5 gene. | sion of yet another homeobox gene in T-ALL further supports the hypothesis that homeobox genes play an important role in malignant transformation of particular types of T-ALL. | 16531254 | [
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The sensitivity of acute lymphoblastic leukemia cells carrying the t(12;21) translocation to campath-1H-mediated cell lysis. | Campath-1H is used in conditioning regimens and more recently as an anti-leukemic therapy in acute lymphoblastic leukemias (ALL). We therefore investigated CD52 expression and campath-1H-mediated lysis of ALL cells in vitro.Complement-mediated cytotoxicity assays were performed on freshly isolated neoplastic cells and cell lines using human serum. Antibody-dependent cellular cytotoxicity (ADCC) was performed by calcein-AM release assays.CD52 was expressed in four out of eight ALL cell lines studied. Among 6 | 16531255 | [
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The sensitivity of acute lymphoblastic leukemia cells carrying the t(12;21) translocation to campath-1H-mediated cell lysis. | 1 freshly isolated ALL samples CD52 was expressed at varying levels in 87% of cases. Whereas ADCC was equivalent in different CD52+ lines; complement-dependent cytotoxicity (CDC) was variable. The REH cell line bearing the t(12;21) translocation showed 47-60% lysis when treated with 10 microg/mL campath-1H compared to 0-6% for the other cell lines expressing equivalent amounts of CD52. Furthermore all nine ALL samples with t(12;21) showed very high CDC (mean 97%) compared to the other 24 CD52+cases (mean 24 | 16531255 | [
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The sensitivity of acute lymphoblastic leukemia cells carrying the t(12;21) translocation to campath-1H-mediated cell lysis. | %)(p<0.0001). In t(12;21) samples; efficient CDC was obtained with as little as 1 microg/mL campath-1H. CDC correlated in part with CD52 levels; suggesting that CD52 expression and other yet undefined factors contribute to the particular sensitivity of t(12;21) cells. The resistance of non t(12;21) ALL cases could be overcome to a limited extent by increasing the concentration of campath-1H; blocking the CD55 and CD59 complement inhibitors; and more effectively by combining campath-1H with fludarabine.We co | 16531255 | [
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The sensitivity of acute lymphoblastic leukemia cells carrying the t(12;21) translocation to campath-1H-mediated cell lysis. | nclude that most ALL samples express CD52 to a variable level and that campath-1H has cytotoxic activity against CD52+ALL; alone or in combination with cytotoxic drugs. | 16531255 | [
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Heterogeneity of neoplastic cells in B-cell chronic lymphoproliferative disorders: biclonality versus intraclonal evolution of a single tumor cell clone. | B-cell chronic lymphoproliferative disorders (B-CLPD) are usually monoclonal expansions of a single B-cell clone. However in some cases; two unrelated B-cell clones co-exist. Additionally; cases with two B-cell subpopulations displaying a similar phenotype but distinct DNA contents exist; the exact nature of these cases remaining unknown. In order to gain insight into the characteristics of these complex B-CLPD we examined two cohorts of patients.One cohort had two phenotypically distinct B-cell populations | 16531256 | [
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Heterogeneity of neoplastic cells in B-cell chronic lymphoproliferative disorders: biclonality versus intraclonal evolution of a single tumor cell clone. | (group A; n= 9) and the other; two B-cell subsets showing different DNA contents and/or light scatter properties; but a similar immunophenotype (group B; n= 7).Fluorescent in situ hybridization studies revealed the presence of genetic abnormalities in six cases from group A; either in one (n=5) or the two co-existing B-cell populations (n=1); in all these cases the two B-cell populations showed unrelated IgH gene rearrangements. In all seven cases from group B; the B-cell population showing higher DNA cont | 16531256 | [
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Heterogeneity of neoplastic cells in B-cell chronic lymphoproliferative disorders: biclonality versus intraclonal evolution of a single tumor cell clone. | ents had additional chromosomal abnormalities as compared to the other subset; molecular analysis confirmed the monoclonal nature of these cases.In summary; we show that in group A; two phenotypically/cytogenetically distinct; unrelated B-cell clones co-exist; while the two B-cell populations from group B appear to represent different stages of evolution of a single clone. | 16531256 | [
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The impact of acute and chronic graft-versus-host disease on normal and malignant B-lymphoid precursors after allogeneic stem cell transplantation for B-lineage acute lymphoblastic leukemia. | The development of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT) for B-lineage acute lymphoblastic leukemia (B-ALL) is associated with a lower probability of leukemia relapse. However; mechanisms by which this GVHD-associated graft-versus-leukemia effect is exerted are poorly understood. In this study; we simultaneously traced the kinetics of normal donor-derived and leukemic recipient-derived B-lymphopoiesis comparing patients with or without GVHD.We used multiparameter | 16531257 | [
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The impact of acute and chronic graft-versus-host disease on normal and malignant B-lymphoid precursors after allogeneic stem cell transplantation for B-lineage acute lymphoblastic leukemia. | flow-cytometry to quantify pro-B (CD19+CD10+CD34+); pre-B (CD19+CD10+CD34-) precursors and malignant lymphoblasts identified by leukemia-associated markers in 161 prospective marrow samples from 39 consecutive B-ALL patients after allogeneic SCT. Chimerism analysis was performed by quantitative real-time polymerase chain reaction of null alleles and insertion/deletion (indel) polymorphisms.Acute GVHD of grades II-IV is associated with a strong inhibition of normal donor-derived pro-B and pre-B precursors at | 16531257 | [
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The impact of acute and chronic graft-versus-host disease on normal and malignant B-lymphoid precursors after allogeneic stem cell transplantation for B-lineage acute lymphoblastic leukemia. | days +30 and +60 post-SCT. Patients who develop chronic GVHD have lower percentages of marrow B-cell precursors during the first year after SCT. Likewise; recipient-derived leukemia B cells were absent at days +30 and +60 in patients with acute GVHD grades II-IV and were less likely to be detected in patients with chronic GVHD. Induction of GVHD as treatment of increasing amounts of leukemia cells causes inhibition of both normal and malignant B compartments even in the absence of steroid therapy.We conclu | 16531257 | [
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The impact of acute and chronic graft-versus-host disease on normal and malignant B-lymphoid precursors after allogeneic stem cell transplantation for B-lineage acute lymphoblastic leukemia. | de that the development of GVHD after allogeneic SCT is associated with a non-specific inhibition of B-lymphopoiesis. | 16531257 | [
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Leukemia-derived dendritic cells: towards clinical vaccination protocols in acute myeloid leukemia. | The ability of acute myeloid leukemic (AML) blasts to differentiate into leukemic dendritic cells (DC) thus acquiring the potential to present known and unknown leukemic antigens efficiently; holds promise as a possible new treatment for AML patients with minimal residual disease. Recent advances in culture methods have made the clinical use of leukemic DC feasible. However; additional measures appear to be essential in order to potentiate vaccines and to overcome the intrinsic tolerant state of the patient | 16531258 | [
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Leukemia-derived dendritic cells: towards clinical vaccination protocols in acute myeloid leukemia. | s immune system. This review describes ways to improve AML-DC vaccines and discusses critical aspects concerning the development of clinical vaccination protocols. | 16531258 | [
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Immunophenotypic heterogeneity of bone marrow-derived mesenchymal stromal cells from patients with hematologic disorders: correlation with bone marrow microenvironment. | The immunophenotypic analysis of ex vivo-expanded mesenchymal stromal cells (MSC) has so far been confined to single or dual staining analysis in normal subjects. In this study; using a four-color cytofluorimetric protocol; we demonstrated that cultured MSC derived from the bone marrow of patients with hematologic malignancies showed alterations in the expression of CD105; CD90; CD184; and HLA-DR molecules. The decrease in the percentage of CD105+ and CD90+ MSC correlated with an increased bone marrow angio | 16531259 | [
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Immunophenotypic heterogeneity of bone marrow-derived mesenchymal stromal cells from patients with hematologic disorders: correlation with bone marrow microenvironment. | genesis. This paper provides evidence that multiparametric flow cytometry is essential for the establishment of a standardized protocol to identify various MSCs subsets and aberrant phenotypes. | 16531259 | [
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Multilineage engraftment of refrozen cord blood hematopoietic progenitors in NOD/SCID mice. | Seven cord blood (CB) units were tested for their capacity to repopulate irradiated NOD/SCID mice after one or two successive cryopreservation procedures. In primary transplants with frozen or refrozen CB cells we observed equivalent human colonies and percentages of human CD45+ cells; with multilineage engraftment. In secondary transplants flow cytometry and polymerase chain reaction for the a satellite region of chromosome 17 showed equivalent levels of human engraftment. Since CB units have; to date; mai | 16531260 | [
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Multilineage engraftment of refrozen cord blood hematopoietic progenitors in NOD/SCID mice. | nly been stored in individual bags; our results suggest new options for optimizing the timing of infusions of expanded and non-expanded progenitors in transplants. | 16531260 | [
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Long-term follow-up of autologous stem cell transplantation after intensive chemotherapy in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. | We report on the outcomes of 53 patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS; autografted in first complete remission. Five (9.4%) died from the procedure whereas hematological reconstitution occurred in all the remaining patients. Forty patients (75%) relapsed; with 87.5% of the relapses occurring within 2 years of the autologous transplant. With a median follow-up of 6.2 years; the median actuarial disease-free survival and overall survival were 8 and 17 months | 16531261 | [
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Long-term follow-up of autologous stem cell transplantation after intensive chemotherapy in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. | after autograft; respectively. Karyotype was the only prognostic factor for disease-free and overall survival. The eight survivors (15%); including two patients with unfavorable or intermediate karyotype; remained in first complete remission 50+ to 119+ months after transplantation and are probably cured. | 16531261 | [
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The role of BCR/ABL isoforms in the presentation and outcome of patients with Philadelphia-positive acute lymphoblastic leukemia: a seven-year update of the GIMEMA 0496 trial. | To verify the potential clinical and prognostic value of BCR/ABL isoforms; we analyzed 101 consecutive adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia enrolled in the GIMEMA 0496 trial between October 1996 and December 1999. A p190 or p210 with or without p190 BCR/ABL transcript was documented in 59 (58.5%) and 42 cases (41.5%); respectively. At diagnosis; a white cell count <16 x 10(9)/L and a higher level of CD34 and CD33 expression were associated with the p190 BCR/ABL t | 16531262 | [
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The role of BCR/ABL isoforms in the presentation and outcome of patients with Philadelphia-positive acute lymphoblastic leukemia: a seven-year update of the GIMEMA 0496 trial. | ranscript (p<0.05; p=0.009 and p=0.03; respectively). A complete remission was achieved in 62/92 (67.4%) patients; while 16/92 (17.4%) were resistant and 14/92 (15.2%) died of therapy-related complications. Fifty-two patients underwent intensive re-induction treatment; which was followed by stem cell transplant consolidation in the 36 in persistent complete remission (allogeneic = 20 patients; autologous = 16 patients). Response rates to induction therapies were similar in the two BCR/ABL isoform groups. By | 16531262 | [
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The role of BCR/ABL isoforms in the presentation and outcome of patients with Philadelphia-positive acute lymphoblastic leukemia: a seven-year update of the GIMEMA 0496 trial. | contrast; the p190 emerged as the only independent prognostic factor favorably affecting the 5-year overall survival and disease-free survival rates (p=0.008 and p=0.02; respectively). | 16531262 | [
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Stimulation of erythropoiesis by thalidomide in multiple myeloma patients: its influence on FasL, TRAIL and their receptors on erythroblasts. | The expression of proteins of the tumor necrosis factor (TNF) family on erythroblasts was measured during thalidomide treatment in 29 patients with multiple myeloma (MM). A clinical response was observed in 17 patients (58.6%) and haemoglobin concentration increased in 22 patients (75.9%). The expression of FasL; Fas; TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL-R1 on erythroblasts decreased significantly during thalidomide treatment. Additional in vitro studies revealed that the apoptosis of ery | 16531263 | [
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Stimulation of erythropoiesis by thalidomide in multiple myeloma patients: its influence on FasL, TRAIL and their receptors on erythroblasts. | throblasts and the expression of FasL; TRAIL; TRAIL-R1 and TRAIL-R2 was lower in cultures with thalidomide than in control cultures. Altogether our results suggest that thalidomide may stimulate erythropoiesis in MM patients by decreasing the expression of TNF-like ligands/receptors on erythroblasts. | 16531263 | [
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Hyperhomocysteinemia and functional cobalamin deficiency due to granulocytosis-induced alterations in the cobalamin-binding protein. | Serum cobalamin and homocysteine levels were studied in patients with chronic myelogenous leukemia (CML) and in stem cell donors treated with granulocyte-colony stimulating factor (G-CSF). Cytoreductive treatment in patients with CML resulted in a decrease of cobalamin and homocysteine levels. In stem cell donors cobalamin and homocysteine levels increased after G-CSF administration. The increase of homocysteine level was accompanied by a decrease in the serum levels of the cobalamin-binding protein transco | 16531264 | [
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Hyperhomocysteinemia and functional cobalamin deficiency due to granulocytosis-induced alterations in the cobalamin-binding protein. | balamin. We hypothesize that the increased homocysteine levels in patients with CML and donors treated with G-CSF may be the result of a functional methylcobalamin deficiency due to decreased transcobalamin levels. | 16531264 | [
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Prognostic value of donor cytotoxic T-lymphocyte precursor frequencies for acute graft-versus-host disease in hematopoietic stem cell transplantation from HLA-matched siblings: a single center experience in a cohort of 92 patients. | We investigated the prognostic value of cytotoxic T-lymphocyte precursor frequencies (CTL-p-f) for the development of graft-versus-host disease (GvHD) in a cohort of 92 recipients of a hematopoietic stem cell transplantation from HLA-matched sibling donors. CTL-p-f and clinical variables were correlated with acute GvHD and chronic GvHD in univariate and multivariate analyses. CTL-p-f resulted an independent risk factor for severe acute GvHD. Moreover; a trend towards a correlation between CTL-p-f and chroni | 16531265 | [
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Prognostic value of donor cytotoxic T-lymphocyte precursor frequencies for acute graft-versus-host disease in hematopoietic stem cell transplantation from HLA-matched siblings: a single center experience in a cohort of 92 patients. | c GvHD was observed. In summary CTL-p-f may be considered as a functional assay useful for identifying patients at high risk of severe GVHD. | 16531265 | [
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The incidence of hemorrhagic cystitis and BK-viruria in allogeneic hematopoietic stem cell recipients according to intensity of the conditioning regimen. | The influence of BK-viruria; donor background; and conditioning on the development of hemorrhagic cystitis was examined in 90 allogeneic hematopoetic stem cell transplant patients; of whom 15 developed hemorrhagic cystitis. Thirty-two patients had related and 58 had unrelated donors; while 44 received full; and 46 received reduced intensity conditioning (RIC). BK-viruria was more common in patients with hemorrhagic cystitis than in those without (p<0.01); and hemorrhagic cystitis was less common in patients | 16531266 | [
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The incidence of hemorrhagic cystitis and BK-viruria in allogeneic hematopoietic stem cell recipients according to intensity of the conditioning regimen. | with related donors than in those with unrelated donors (p=0.02). Finally; hemorrhagic cystitis and BK-viruria were less common in patients receiving RIC; rather than full conditioning (p<0.01 and p<0.01; respectively). | 16531266 | [
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The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease. | Acute graft-versus-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation. We performed a phase II study on patients with acute steroid-refractory GVHD grades II to IV given extracorporeal photochemotherapy (ECP) weekly and analyzed response and long-term survival. Complete resolution of GVHD was achieved in 82% of patients with cutaneous involvement; 61% with liver involvement; and 61% with gut involvement. The probability of survival was 59% among patien | 16531267 | [
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The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease. | ts who responded completely to ECP compared to 11% in patients not responding completely. We conclude that intensified ECP is highly effective in acute GVHD and that sustained responses are associated with over 50% long-term survival. | 16531267 | [
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A longitudinal study of the JAK2(V617F) mutation in myelofibrosis with myeloid metaplasia: analysis at two time points. | Serial analysis for the activating JAK2(V617F) mutation performed in 44 patients with myelofibrosis with myeloid metaplasia showed no interval change in 88% (22/25) of patients over a median interval of 18.6 months. The increase in JAK2 expression observed in three patients did not correspond to disease progression or leukemic transformation. | 16531268 | [
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The value of autofluorescence as a diagnostic feature of acute promyelocytic leukemia. | Autofluorescence is an immunophenotypic characteristic of leukemic blasts in acute promyelocytic leukemia (APL). We examined the fluorescent intensity of isotype controls in 25 cases of APML and 25 controls with acute myeloid leukemia. The fluorescence of the FITC- and PE-conjugated controls was consistently higher in APML. Autofluorescence may therefore represent a helpful diagnostic marker in APML. | 16531269 | [
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Molecular response in two children with relapsed acute myeloid leukemia treated with a combination of gemtuzumab ozogamicin and cytarabine. | Phase I/II studies of gemtuzumab ozogamicin (GO) in pediatric refractory/relapsed acute myeloid leukemia (AML) have been reported. We present the cases of two children with relapsed AML who were treated with GO plus cytarabine; leading to a decrease of minimal residual disease down to levels not previously obtained. The toxicity profile of this treatment was relatively mild; except for severe but manageable myelosuppression. | 16531270 | [
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Characterization of the t(17;19) translocation by gene-specific fluorescent in situ hybridization-based cytogenetics and detection of the E2A-HLF fusion transcript and protein in patients' cells. | This is the first report to comprehensively characterize the E2A-HLF fusion generated from the t(17;19)(q22;p13) translocation in childhood B-lineage acute lymphoblastic leukemia. E2A gene rearrangement and E2A-HLF transcript and protein expression were determined using conventional cytogenetics; fluorescent in situ hybridization; reverse transcriptase polymerase chain reaction and Western blotting in leukemic cells from three patients. | 16531271 | [
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Rituximab and DHAP followed by intensive therapy with autologous stem-cell transplantation as first-line therapy for mantle cell lymphoma. | We report on a series of 24 patients with newly diagnosed mantle cell lymphoma treated with four to six courses of DHAP-rituximab followed by autologous stem cell transplantation for patients <65 years. Three-year overall survival (OS) and event free survival (EFS) rates were 69% and 65% respectively; for the 24 patients. In intent-to-treat analysis; 3-year OS and EFS were 75% and 76% for the 17 patients < 65 years old. This treatment is quite feasible and compares favourably with other regimens. | 16531272 | [
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The diagnostic value of cerebrospinal fluid pleocytosis and protein in the detection of lymphomatous meningitis in primary central nervous system lymphomas. | The exact rate of lymphomatous meningitis in primary central nervous system lymphomas (PCNSL) is uncertain. In this prospective multicenter study; cerebrospinal fluid (CSF) from 116 immunocompetent patients with newly diagnosed PCNSL was evaluated. Lymphoma cells were found in 18.1%; protein elevation (>45 mg/dL) in 65%; and CSF pleocytosis (>5/microL) in 36% of patients. Pleocytosis correlated with positive cytology; whereas CSF protein did not (specificity cell count vs. protein 74% vs. 34% [p<0.001]; sen | 16531273 | [
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The diagnostic value of cerebrospinal fluid pleocytosis and protein in the detection of lymphomatous meningitis in primary central nervous system lymphomas. | sitivity 86% vs. 62% [p=0.18]). | 16531273 | [
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BCL2 family of apoptosis-related genes: functions and clinical implications in cancer. | One of the most effective ways to combat different types of cancer is through early diagnosis and administration of effective treatment; followed by efficient monitoring that will allow physicians to detect relapsing disease and treat it at the earliest possible time. Apoptosis; a normal physiological form of cell death; is critically involved in the regulation of cellular homeostasis. Dysregulation of programmed cell death mechanisms plays an important role in the pathogenesis and progression of cancer as | 16531274 | [
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BCL2 family of apoptosis-related genes: functions and clinical implications in cancer. | well as in the responses of tumours to therapeutic interventions. Many members of the BCL2 (B-cell CLL/lymphoma 2; Bcl-2) family of apoptosis-related genes have been found to be differentially expressed in various malignancies; and some are useful prognostic cancer biomarkers. We have recently cloned a new member of this family; BCL2L12; which was found to be differentially expressed in many tumours. Most of the BCL2 family genes have been found to play a central regulatory role in apoptosis induction. Resu | 16531274 | [
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] |
BCL2 family of apoptosis-related genes: functions and clinical implications in cancer. | lts have made it clear that a number of coordinating alterations in the BCL2 family of genes must occur to inhibit apoptosis and provoke carcinogenesis in a wide variety of cancers. However; more research is required to increase our understanding of the extent to which and the mechanisms by which they are involved in cancer development; providing the basis for earlier and more accurate cancer diagnosis; prognosis and therapeutic intervention that targets the apoptosis pathways. In the present review; we des | 16531274 | [
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BCL2 family of apoptosis-related genes: functions and clinical implications in cancer. | cribe current knowledge of the function and molecular characteristics of a series of classic but also newly discovered genes of the BCL2 family as well as their implications in cancer development; prognosis and treatment. | 16531274 | [
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The molecular diagnosis of hepatitis B virus-associated hepatocellular carcinoma. | Hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC) worldwide. The pathogenesis of HBV-associated HCC has been studied extensively; and molecular changes during malignant transformation have been identified. It has been proposed that the insertion of HBV DNA into the human genome results in chromosomal instability and inactivation of tumor suppressor genes. Transactivation of oncogenes; inactivation of tumor suppressor genes; and alteration of the cell cycle by HBV protein | 16531275 | [
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The molecular diagnosis of hepatitis B virus-associated hepatocellular carcinoma. | s are also involved in the progression of hepatocellular carcinogenesis. Traditional clinical examinations of HCC; such as biopsy; computer tomography; ultrasonic imaging; and detection of such biomarkers as a-fetoprotein; are currently the "gold standard" in diagnosis. These tests diagnose HCC only in the late stages of disease. This limitation has greatly reduced the chance of survival of HCC patients. To resolve this problem; new biomarkers that can diagnose HCC in earlier stages are necessary. Based on | 16531275 | [
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