bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hematopoietic Development from Human Embryonic Stem Cells
Authors: Bhatia Mickie 
Published: November 2007

AbstractThe most common human cell-based therapy applied today is hematopoietic stem cell (HSC) transplantation. HSCs can be defined by two essential properties: self-renewal and multilineage hematopoietic differentiation. These combined HSC properties allow them to differentiate into all blood cell types (multilineage) in a sustained manner for the lifetime of the animal, which requires their ability to make cellular copies of themselves (self-renewal). These features can be tested by transplantation from donor to recipient and provide a functional basis to define and identify HSCs. Currently, human bone marrow (BM), mobilized peripheral blood, and umbilical cord blood (CB) represent the major sources of transplantable HSCs, but their availability for use is limited by both quantity and compatibility. Although increasing evidence suggests that somatic HSCs can be expanded to meet current needs, their in vivo potential is concomitantly compromised after ex vivo culture. Pluripotent human embryonic stem cells (hESCs) may provide an alternative. hESCs possess indefinite proliferative capacity in vitro, and have been shown to differentiate into the hematopoietic cell fate, giving rise to erythroid, myeloid, and lymphoid lineages using a variety of differentiation procedures. In most cases, hESC-derived hematopoietic cells show similar clonogenic progenitor capacity and primitive phenotype to somatic sources of hematopoietic progenitors, but possess limited in vivo repopulating capacity when transplanted into immunodeficient mice. Although this suggests HSC function can be derived from hESCs, the efficiency and quality of these cells must be characterized using surrogate models for potential clinical applications.
Antibody Therapy in Aggressive Lymphomas
Authors: Habermann Thomas M. 
Published: November 2007

AbstractThe aggressive lymphomas are potentially curable. The natural history of certain aggressive lymphomas has been altered by monoclonal antibody therapy. Targeted monoclonal antibody therapy to the CD20 antigen has altered the outcome of patients with diffuse large B-cell lymphoma in patients of all ages. Anti-CD20–based radioimmunoconjugates are being evaluated as radioimmunotherapy approaches in patients who have relapsed and in stem cell transplant settings. Antibody-directed therapy to the B-cell–specific antigen CD22 are ongoing. New approaches include different CD20 antibodies and an antibody to the CD40 antigen, which is a member of the tumor necrosis factor (TNF) receptor family, which is expressed on B-cells. Antibody therapy has been incorporated into CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) therapy and other regimens such as EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) and HyperCVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone). Single-agent anti-CD20 therapy is active in the post-transplantation lymphoproliferative disorders. T-cell antibodies are under evaluation in a number of T-cell lymphoproliferative disorders. Targeted therapy has changed the natural history of a number of aggressive non-Hodgkin lymphomas. This review will describe the contributions of antibody therapies to the treatment of these diseases.
Stem Cell Transplantation in Multiple Myeloma
Authors: Attal Michel , Moreau Philippe , Avet-Loiseau Herve , Harousseau Jean-Luc 
Published: November 2007

AbstractMultiple myeloma (MM) is one of the key hematologic malignancies in which the impact of dose intensity has been demonstrated. Consequently, in 2005, MM was the most common disease for which autologous stem cell transplantation (ASCT) was indicated both in Europe and in the U.S. However, ASCT is not curative, and most patients relapse within a median of 3 years. Novel agents such as thalidomide (Thalidomid), bortezomib (Velcade), or lenalidomide (Revlimid) have been introduced to improve high-dose therapy, and promising results have been reported. Conversely, results from myeloablative allogeneic stem cell transplantation remain disappointing due to high transplantation-related mortality, justifying the exploration of strategies such as reduced-intensity conditioning, which have been shown to be feasible but for which proof of efficacy requires continued study.
The Biology of CML Blast Crisis
Authors: Radich Jerald P. 
Published: November 2007

AbstractThe natural history of chronic myeloid leukemia (CML) progresses from a relatively benign chronic phase into a fatal blast crisis, which resembles acute leukemia, but is incurable by chemotherapy. Fortunately, the progression can usually be blocked by tyrosine kinase therapy or allogeneic transplantation. The seemingly stereotypical march of progression involves changes in genetic instability and DNA repair, proliferation, differentiation, and apoptosis, and thus may serve as a unique model of cancer evolution and progression. Given that all treatments work much better in chronic-phase than advanced-phase disease, the clinical dilemma is predicting and detecting patients bound to evolve into advanced disease. This is especially important in the age of tyrosine kinase inhibition (TKI) therapy. The purpose of this review is to address the biology of blast crisis in the age of tyrosine kinase therapy, with an emphasis on what genes or pathways may be future targets of predictive assays or treatments of progression.
Modifying the Epigenome as a Therapeutic Strategy in Myelodysplasia
Authors: Garcia-Manero Guillermo 
Published: November 2007

AbstractThe term epigenetics refers to a number of biochemical modifications of chromatin that, without altering the primary sequence of DNA, have a role in genomic regulation and in particular gene expression control. These modifications can occur at the DNA level (i.e., DNA methylation), and affect the chromatin protein scaffold (i.e., histone code modifications), among several others. The study of these modifications is a very active area of research both at the basic and clinical levels. Clinical interest in these epigenetic alterations stems mainly from two observations. First, detection of specific epigenetic alterations could be used to develop cancer biomarkers (e.g., for the early detection or prognostication of cancer). Second, most epigenetic alterations are reversible both in vitro and in vivo, leading the way to the development of new anticancer therapies. This review focuses on the current clinical information regarding different forms of epigenetic therapy in patients with myelodysplastic syndromes (MDS). Basic aspects of DNA methylation or histone code alterations are not covered in detail in this review.
Targeting Treatment in AML
Authors: Burnett Alan K. , Knapper Steve 
Published: November 2007

AbstractCurrently available chemotherapy has probably reached the limits of its potential in treating acute myeloid leukemia (AML). In considering the next steps it is appropriate to exploit on the one hand knowledge of the molecular, immunophenotypic and biological characteristics of the disease and on the other the biology of the patient. The aim is to move towards a more targeted approach.Immunophenotyping has defined an adequate target (CD33) for antibody-directed treatment, although this is not leukemia specific. Monotherapy has produced important response rates in relapsed disease but it is unlikely to displace conventional chemotherapy. Several randomized trials of antibody directed chemotherapy in combination with chemotherapy nearing completion will establish the usefulness of this approach. In most patients a leukemia-specific immunophenotype can be characterized that can be used to monitor treatment. Minimal residual disease (MRD) detection in morphological remission can detect patients at high risk of relapse, as can a limited number of molecular markers. The clinical value of intervening at the time of MRD detection is not clear. Among the increasing molecular abnormalities described in AML, FLT-3 mutations appear the most attractive for therapeutic intervention. Several phase 2 studies have shown limited efficacy, and randomized trials in combination are underway. Other mechanisms that can be specifically targeted include farnesylation, methylation status, and histone deacelylation. Newer knowledge about the immunophenotypic and biological characteristics of the leukemic stem cell population has opened opportunities to develop treatments that exploit characteristics of the leukemic stem cells that differ from the normal stem cell. Some of these initiatives are now discussed.
The Yin and Yang of Stem Cell Gene Therapy: Insights into Hematopoiesis, Leukemogenesis, and Gene Therapy Safety
Authors: Dunbar Cynthia E. 
Published: November 2007

Abstract
Over the past decade, success in the treatment of serious genetic disorders via gene therapy was finally achieved. However, this progress was tempered by the occurrence of serious adverse events related to vector integration into the genome and activation of adjacent proto-oncogenes. Investigators are now focused on retaining the clinical potential of integrating vectors while decreasing the risk of insertional mutagenesis.
Trials and Tribulations of Systematic Reviews and Meta-Analyses
Authors: Crowther Mark A. , Cook Deborah J. 
Published: November 2007

Abstract
Systematic reviews can help practitioners keep abreast of the medical literature by summarizing large bodies of evidence and helping to explain differences among studies on the same question. A systematic review involves the application of scientific strategies, in ways that limit bias, to the assembly, critical appraisal, and synthesis of all relevant studies that address a specific clinical question. A meta-analysis is a type of systematic review that uses statistical methods to combine and summarize the results of several primary studies. Because the review process itself (like any other type of research) is subject to bias, a useful review requires rigorous methods that are clearly reported. Used increasingly to inform medical decision making, plan future research agendas, and establish clinical policy, systematic reviews may strengthen the link between best research evidence and optimal health care. In this article, we discuss key steps in how to critically appraise and how to conduct a systematic review or meta-analysis.
Coagulation in the Pathophysiology of Hemolytic Anemias
Authors: Cappellini Maria Domenica 
Published: November 2007

AbstractCoagulation abnormalities are frequently reported in hemolytic anemias (HA). Several pathophysiologic mechanisms are common to different HA. In this review three different hemolytic disorders will be discussed.In sickle cell disease and in β-thalassemia, a thrombophilic status has been well documented as multifactorial involving hemostatic changes and activation of the coagulation cascade. Moreover, in such disorders, elevated levels of endothelial adhesion protein (ICAM-1, ELAM-1, VCAM-1, von Willebrand factor, and thrombomodulin) are often increased, suggesting that endothelial activation may be involved in vascular occlusion. As an additional mechanism of hypercoagulability in thalassemia, a procoagulant status of thalassemic red cells was recognized.The main clinical manifestation of paroxysmal nocturnal hemoglobinuria (PNH) is HA, and the most common complications are thrombosis, pancytopenia, and myelodysplastic syndrome or acute leukemia. The intravascular hemolysis is explained by a deficiency of glycosil phosphatidylinositol (GPI)-anchored complement regulatory proteins such as CD59 and CD55 on the membrane of red blood cells (RBCs), but the mechanism responsible for the increased incidence of thrombotic events in PNH remains unclear.Recent advances have been made in understanding the coagulation involvement in a heterogeneous group of diseases, thrombotic microangiopathies (TMA) characterized by microangiopathic hemolytic anemia and thrombocytopenia due to platelet clumping in the microcirculation, leading to ischemic organ dysfunction with neurologic symptoms and renal impairment.
Current Issues in Sickle Cell Pain and Its Management
Authors: Ballas Samir K. 
Published: November 2007

AbstractPain is the insignia of sickle cell disease and the acute painful crisis is the number-one cause of hospital admissions. Tissue damage due to vaso-occlusion releases numerous inflammatory mediators that initiate the transmission of painful stimuli and the perception of pain. The acute sickle cell painful crisis evolves along four distinct phases coupled with changes in certain markers of the disease. Hospital readmission within 1 week occurs in about 16% of discharged patients. Failure to treat acute pain aggressively may lead to chronic pain syndrome. Management of sickle pain is primarily pharmacologic in nature, and opioids are the analgesics used most often. Cellular and molecular mechanisms of opioids explain individual differences among patients and justify the use of individualized treatment plans.
Identification of single nucleotide polymorphisms in bovine CARD15 and their associations with health and production traits in Canadian Holsteins
Authors: Pant Sameer D , Schenkel Flavio S , Leyva-Baca Ivan , Sharma Bhawani S , Karrow Niel A 
Published: November 2007

Abstract

Background
Toll-like receptor-2 (TLR2) and Caspase Recruitment Domain 15 (CARD15) are important pattern recognition receptors that play a role in the initiation of the inflammatory and subsequent immune response. They have been previously identified as susceptibility loci for inflammatory bowel diseases in humans and are, therefore, suitable candidate genes for inflammatory disease resistance in cattle. The objective of this study was to identify single nucleotide polymorphisms (SNPs) in the bovine TLR2 and CARD15 and evaluate the association of these SNPs with health and production traits in a population of Canadian Holstein bulls.

Results
A selective DNA pool was constructed based on the estimated breeding values (EBVs) for SCS. Gene segments were amplified from this pool in PCR reactions and the amplicons sequenced to reveal polymorphisms. A total of four SNPs, including one in intron 10 (c.2886-14A>G) and three in the exon 12 (c.3020A>T, c.4500A>C and c.4950C>T) were identified in CARD15; none were identified in TLR2. Canadian Holstein bulls (n = 338) were genotyped and haplotypes were reconstructed. Two SNPs, c.3020A>T and c.4500A>C, were associated with EBVs for health and production traits. The SNP, c.3020A>T, for example, was associated with SCS EBVs (p = 0.0097) with an allele substitution effect of 0.07 score. When compared to the most frequent haplotype Hap12(AC), Hap22(TC) was associated with increased milk (p < 0.0001) and protein (p = 0.0007) yield EBVs, and hap21(TA) was significantly associated with increased SCS EBV(p = 0.0120). All significant comparison-wise associations retained significance at 8% experimental-wise level by permutation test.

Conclusion
This study indicates that SNP c.3020A>T might play a role in the host response against mastitis and further detailed studies are needed to understand its functional mechanisms.
Bursts and horizontal evolution of DNA transposons in the speciation of pseudotetraploid salmonids
Authors: de Boer Johan G , Yazawa Ryosuke , Davidson William S , Koop Ben F 
Published: November 2007

Abstract

Background
Several genome duplications have occurred in the evolutionary history of teleost fish. In returning to a stable diploid state, the polyploid genome reorganized, and large portions are lost, while the fish lines evolved to numerous species. Large scale transposon movement has been postulated to play an important role in the genome reorganization process. We analyzed the DNA sequence of several large loci in Salmo salar and other species for the presence of DNA transposon families.

Results
We have identified bursts of activity of 14 families of DNA transposons (12 Tc1-like and 2 piggyBac-like families, including 11 novel ones) in genome sequences of Salmo salar. Several of these families have similar sequences in a number of closely and distantly related fish, lamprey, and frog species as well as in the parasite Schistosoma japonicum. Analysis of sequence similarities between copies within the families of these bursts demonstrates several waves of transposition activities coinciding with salmonid species divergence. Tc1-like families show a master gene-like copying process, illustrated by extensive but short burst of copying activity, while the piggyBac-like families show a more random copying pattern. Recent families may include copies with an open reading frame for an active transposase enzyme.

Conclusion
We have identified defined bursts of transposon activity that make use of master-slave and random mechanisms. The bursts occur well after hypothesized polyploidy events and coincide with speciation events. Parasite-mediated lateral transfer of transposons are implicated.
Recent Developments in Hydraulic Couplings
Authors: Sinclair Harold 
Published: November 2007

The use of hydraulic couplings in practically all fields of engineering has increased rapidly during the last few years. The paper traces the history of the Vulcan-Sinclair hydraulic coupling, which is of the turbo or hydro-kinetic type, from the days of its inception up to the present time, and gives details of other designs of the displacement or hydro-static type that have been developed, and the principles upon which they operate. The main advantages of the turbo design are enumerated and considerable test data are given, with particular reference to the Vulcan coupling, which, in theory, is the forerunner of the Vulcan-Sinclair designs. Advantage is taken to explain the difference between fluid couplings and torque converters, concerning which a good deal of confusion exists. The differences between the various types of Vulcan-Sinclair hydraulic couplings and the improvements that have been effected in design during recent years are described in detail. The paper deals comprehensively with numerous applications of the different types of couplings covering both the industrial and automotive fields. The difficulties, and their cures, which have arisen in connexion with a number of applications are given prominence. A section deals with change-speed gearboxes arranged in conjunction with hydraulic couplings for use in Diesel traction.
P-Selectin–Coated Microtube for Enrichment of CD34+ Hematopoietic Stem and Progenitor Cells from Human Bone Marrow
Authors: Narasipura Srinivas D , Wojciechowski Joel C , Charles Nichola , Liesveld Jane L , King Michael R 
Published: November 2007

Abstract
Background: Enrichment and purification of hematopoietic stem and progenitor cells (HSPCs) is important in transplantation therapies for hematologic disorders and in basic stem cell research. Primitive CD34+ HSPCs have demonstrated stronger rolling adhesion on selectins than mature CD34− mononuclear cells (MNCs). We have exploited this differential rolling behavior to capture and purify HSPCs from bone marrow by perfusing MNCs through selectin-coated microtubes.
Methods: Bone marrow MNCs were perfused through the cell-capture microtubes coated with adhesion molecules. We washed the device lumen and visualized and estimated captured cells by video microscopy. Adherent cells were eluted by high shear, calcium-free buffer, and air embolism. We used immunofluorescence staining followed by flow cytometry to analyze CD34+ HSPCs.
Results: CD34+ HSPC purity of cells captured in adhesion molecule–coated devices was significantly higher than the fraction of CD34+ cells found in bone marrow MNCs [mean (SE) 2.5% (0.8%)]. P-selectin–coated surfaces yielded 16% to 20% CD34+ cell purity, whereas antibody-coated surfaces yielded 12% to 18%. Although CD34+ cell purity was comparable between selectin and antibody surfaces, the total number of CD34+ HSPCs captured was significantly higher in P-selectin devices (approximately 5.7 × 104 to 7.1 × 104) than antibody devices (approximately 1.74 × 104 to 2.61 × 104).
Conclusions: P-selectin can be used in a compact flow device to capture HSPCs. Selectin-mediated capture of CD34+ HSPCs resulted in enrichment approximately 8-fold higher than the CD34+ cell population from bone marrow MNCs. This study supports the hypothesis that flow-based, adhesion molecule–mediated capture may be a viable alternative approach to the capture and purification of HSPCs.
Ultraviolet B radiation induces cell shrinkage and increases osmolyte transporter mRNA expression and osmolyte uptake in HaCaT keratinocytes
Authors: Warskulat Ulrich , Brookmann Stefanie , Reinen Andrea , Häussinger Dieter 
Published: November 2007

Abstract
We have previously shown that compatible organic osmolytes, such as betaine, myo-inositol and taurine, are part of the stress response of normal human keratinocytes (NHKs) to ultraviolet B (UVB) radiation. In this regard, we tested human HaCaT keratinocytes as a surrogate cell line for NHK. HaCaT cells osmo-dependently express mRNA specific for transport proteins for betaine (BGT-1), myo-inositol (SMIT) and taurine (TAUT). Compared to normoosmotic (305 mosmol/l) controls, which strongly constitutively expressed BGT-1 mRNA, strong induction of SMIT and TAUT mRNA as well as low induction of BGT-1 mRNA expression was observed between 3 and 9 h after hyperosmotic exposure (405 mosmol/l). This expression correlated with an increased osmolyte uptake. Conversely, hypoosmotic (205 mosmol/l) stimulation led to a significant efflux of osmolytes. Exposure to UVB (290–315 nm) radiation induced cell shrinkage which was followed by an upregulation of osmolyte transporter mRNA levels and osmolyte uptake. These results demonstrate that human HaCaT keratinocytes possess an osmolyte strategy including UVB-induced cell shrinkage and following increased osmolyte uptake. However, several differences in osmolyte transporter expression and uptake were noted between NHK and HaCaT cells, indicating that the use of HaCaT cells as a surrogate cell line for NHK has limitations.
FOXM1, a typical proliferation-associated transcription factor
Authors: Wierstra Inken , Alves Jürgen 
Published: November 2007

Abstract
FOXM1 is a typical proliferation-associated transcription factor: it stimulates proliferation by promoting S-phase entry as well as M-phase entry and is involved in proper execution of mitosis. Accordingly, FOXM1 regulates genes that control G1/S-transition, S-phase progression, G2/M-transition and M-phase progression. Consistently, its expression and its activity are antagonistically regulated by many important proliferation and anti-proliferation signals. Furthermore, FOXM1 is implicated in tumorigenesis and contributes to both tumor initiation and progression. In addition to its function as a conventional transcription factor, FOXM1 transactivates the human c-myc P1 and P2 promoters directly via their TATA-boxes by a new transactivation mechanism, which it also employs for transactivation of the human c-fos, hsp70 and histone H2B/a promoters. This review summarizes the current knowledge on FOXM1, in particular its two different transactivation mechanisms, the regulation of its transcriptional activity by proliferation versus anti-proliferation signals and its function in normal cell cycle progression and tumorigenesis.