bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Haemostatic Properties of Diverse Haematophagous Hirudinea from around the World Could Have New Therapeutic Potentials.
Authors: Wakeman Lisa , Munro Roger , Al-Ismail Saad 
Published: October 2019

Abstract
The purpose of this study was to survey the anti-haemostatic nature of cephalic extracts prepared from phylogenetically diverse rhyncobdellid (proboscis-bearing) and arhynchobdellid (jawed) leeches and to evaluate the significance in the context of their evolutionary development. Cephalic extracts from specimens of each species were prepared by homogenising in tris buffer the anterior one-third region of the bodies containing the salivary glands. In the case of the giant leech Haementeria ghilianii, paired anterior salivary glands were removed by excision through the oesophagus. The posterior musculature served as control material. Homogenates were double-centrifuged and supernatants micro-filtered. Individual extracts (or imidazole buffer as control) were pre-incubated 1:4 with pooled normal citrated plasma for 5 minutes prior to testing for inhibition of coagulation or with platelet rich plasma prior to assessing their effect on platelet aggregation. All extracts were kept on ice and tested within 1 hour of preparation. Coagulation screening tests using Dade-Behring reagents on a Sysmex CA-1500 coagulometer included PT, APTT, thrombin clotting time, atroxin clotting time, euglobulin clot lysis and anti-Xa assay. Collagen (2μg/ml) and ADP (5μM) were used as inducers of platelet aggregation. The species of leeches examined and their country of origin were:
Proboscid Leeches Source Sub-Family Haementeria ghilianii Brazil Haementeriinae Oosthuizobdella garoui South Africa Haementeriinae Placobdella parasitica Canada Glossiphoniinae Jawed Leeches Macrobdella decora N. America Macrobdellinae Hirudinaria manillensis China Hirudinariinae Hirudinaria javanica Indonesia Hirudinariinae Poecilobdella granulosa India Hirudinariinae Myxobdella africana Kenya Praodbellinae
Our findings indicate that cephalic extracts from all the species examined contain anti-thrombin properties. However, only the giant leech H. ghilianii appears to possess fibrin(ogen)olytic activity. No evidence of a plasminogen activator was detected in any of the extracts. Platelet aggregation responses induced by both agonists were completely inhibited in the presence of all cephalic extracts. No such inhibition was detectable in the posterior musculature control material. Anti-Factor Xa activity was present in extracts from H. ghilianii. Our findings suggest that anti-haemostatic properties in Hirudinea appear to have evolved in response to biological adaptations rather than in keeping with phylogenetic affinities but further work is required to define the precise nature of such mechanisms in related species The different anti-haemostatic properties in these extracts may offer new therapeutic potentials.
Carotid and Vertebral Artery Dissection Syndromes.
Authors: Grand Beatriz , Solimano Jorge , Ventura Adriana , Micheo Ernesto Quiroga , Riveros Dardo 
Published: October 2019

Abstract
Objetives: To describe the clinical presentation, diagnosis and treatment of patients with carotid and vertebral artery dissection (CAD, VAD).
Design: Retrospective, observational
Patients and methods: Clinical recording were evaluated from 1996 to 2005; 6 patients (3 women, 3 men, mean age 37 years) with CAD (3) and VAD (3) were referred to our hematology unit.
Clinical presentation: progressing stroke 4/6 and transient ischemic attack (TIA) 2/6; warning sings and symptoms preceding the onset of stroke in 80%. Vascular risk factors included smoking and hypertension; associated features were headache, visual symptoms and Horner’s syndrome; Predisposing factors as physical exercise and trauma were found in 4/6. One patient was at 20 weeks of pregnancy.
Diagnosis: Diagnostic tests included: Doppler ultrasound, magnetic resonance imaging (MRI) and angiography (MRA). On admission angiographic studies showed occlusion or stenoses of dissected arteries.
Treatment: Anticoagulation with heparin or low molecular weight heparin followed by oral anticoagulants.
Outcome: No hemorrhagic complication, no recurrence, complete recovery in 5 patients and mild dysarthria in one.
Conclusion: TIA and progressing stroke in young patients are presenting features of CAD and VAD. The diagnosis is based on clinical signs and confirming angiographic investigation. Our experience shows that anticoagulation is the treatment of choice, although controlled studies to show their effectiveness are lacking.
Pharmaco-Economic Impact of Transfusion and Erythropoietin (EPO) Administration for Patients Having Myelodysplastic Syndromes (MDS) in an Hematology Department.
Authors: Rossi Jean-Francois , Lopez Ernesto , Kanouni Tarik , Navarro Robert , Borghero Marc , Latry Pascal 
Published: October 2019

Abstract
The University Hospital of Montpellier is the major university hospital in Languedoc-Roussillon, a region with 2.4 milions of inhabitants including 23–26% of the population having more than 65 years. This hospital includes 1015 beds and places in medicine, and 809 in surgery. Total cost of the products for transfusion concerning the hospital is 7 7606 121$. For the hematology department (56 beds, with 130–150 transplantations per year), the cost of the transfusion products represents 39.53% of the whole budget. 21.26% of the total expenditure of red blood cell (RBC) transfusion and 70.17% of the total expenditure of platelet transfusion are from this hematology department. The outpatient clinic of the department (12 beds) is the major localization for transfusing patients with MDS, representing around 20% of the activity in this part of the department. The total fee of transfusion products for this outpatient clinic is 798 739 $ with 351 464$ for RBC transfusion, representing 44%, while RBC transfusion represents 28% of the activity for the whole department, with 19.7% of increase between 2003 and 2004. The activity of hematology is linked to 2 other sites for outpatient and hospitalization in the region of Languedoc-Roussillon (including 35+10 additional beds). Similar increase of the transfusion was observed. New system of price list concerning medical activity in hospitals has been established in France, with a transfusion price fixed at 873$. By using this new accounting, transfusion appears to be slightly in deficit for an outpatient clinic in a university hospital such ours, considering the other medical activities, particularly transplantation and ambulatory chemotherapy. In addition, the number of patients with MDS is increasing in the region, according to the increase of elderness and number of treated cancers. From 01/02 to 04/05, we treat new patients having MDS, excluding AREB-t, by EPO, subcutaneously, from 12 000 to 60 000 UI per week. 85 patients entered this study. The response rate was based on an increase of hemoglobin level superior or equal to 1.5g%, or a reduction superior or equal to 30% of the transfusion consumption observed for more than 6 months. 22% of the patients reached one of these criteria, with 35% of the patients having refractory anemia (RA), sideroblastic RA or 5q- RA and only 12% of the patients having AREB. Only 5% of the patients transfused had a benefit of EPO. In some patients, we observed a dose effect of EPO between 10 000 and 40 000 UI, but at a lesser extend between 40 to 60 000 UI per week, and lasting less than 3 months. Mean duration of the effect was 1.6 year, depending the transformation risk. Benefit of EPO was not correlated with the hemoglobin level at the inclusion but to the status of MDS. Whole data concerning the indirect and direct costs will be presented for this cohort.
A Novel Method for Efficient Production of Multipotential Hematopoietic Progenitors from Human Embryonic Stem Cells by Co-Culture with Murine Fetal Liver-Derived Stromal Cells.
Authors: Ma Feng , Wang Dan , Hanada Sachiyo , Kawasaki Hirohide , Zaike Yuji , Heike Toshio , Kitamura Toshio , Nakahata Tatsutoshi , Tsuji Kohichiro 
Published: October 2019

Abstract
Human embryonic stem cells provide a unique tool to study early events occurring in the development of human embryonic hematopoiesis, and their totipotent capability indicates a potent clinical application based on the cellular therapy and the evaluation of drug effects on hematopoietic and blood cells. To achieve efficient production of hematopoietic cells from human embryonic stem cells, we attempted to reproduce the circumstance surrounding embryonic hematopoietic cells in vitro. Since fetal liver is the predominant source of hematopoietic and blood cells in mammalian embryogenesis, we established stromal cells from mouse fetal liver at days 14 to 15 of gestation. In the co-culture of human embryonic stem cells with the established stromal cells, a number of hematopoietic progenitors were generated at around day 14 of co-culture, and this hematopoietic activity was highly enriched in the cobble stone-like cells under the stromal layer. Most of the cobble stone-like cells collected expressed CD34 and contained a variety of hematopoietic colony-forming cells, especially multilineage colony-forming cells, at a high frequency. The multipotential hematopoietic progenitors in the cobble stone-like cells produced all types of mature blood cells, including adult type hemoglobin-synthesizing erythrocytes and tryptase and chymase-bouble positive mast cells in the suspension cultiue with a cytokine cocktail. The developed co-culture system of human embryonic stem cells should offer a novel source for hematopoietic and blood cells applicable to cellular therapies and drug screening.
A Gene-Targeted Mouse Model for Bone Marrow Failure Syndrome.
Authors: Kasai Masataka , Fukuda Yuko , Ishida Reiko 
Published: October 2019

Abstract
Bone marrow failure is a disease syndrome characterized by dysfunction of bone marrow to produce mature blood cells. However, molecular mechanisms causing the disease syndromes remain remarkably obscure. We generated mice homozygous for an inactivating mutation of the Translin gene. Most of the aged mutant mice (Translin−/−) were found to exhibit progressive bone marrow dysfunction manifested by a reduction in immature myeloid cells and erythroblasts, and eventually developed marked splenomegaly, with up to 30-fold elevation in weight. Histological examination of enlarged spleens revealed extramedullary hematopoiesis, prominent expansion of the red pulp areas with an increase in the number of mature granulocytes and a marked lack of immature myeloid cells. Furthermore, these mice also featured complete loss of immature myeloid cells and erythroblasts in bone marrow. On the other hand, an increase in the number of reticulocytes (over 10 %) and unusual appearance of metamyelocytes and orthochromatic erythroblasts were seen in peripheral blood. A cascade of the lineage-restricted transcription factors is known to determine developmental decisions regarding hematopoiesis. How levels of transcription factors are translated into a decision to control lineage commitment is an intriguing question in hematopoiesis which remains to be explored. Therefore, we considered the bone marrow failure in aged Translin−/− might be due to decreased expression of the Ets family transcription factor PU.1 that has previously been suggested to be essential for myeloid development. However, quantitative RT-PCR analysis showed PU.1 mRNA to be expressed at equivalent levels in bone marrows of mutant and wild mice. In contrast, our data indicated a sharp reduction of the mRNA levels of the basic helix-loop-helix (bHLH) protein, E2A and its dimerization partner, TAL1, suggesting a contribution of E47/TAL heterodimer having distinctive DNA-binding properties for fine tune control of gene expression during hematopoiesis. In conclusion, the present studies demonstrated that expression levels of Translin are crucial to the bone marrow’s functional ability, and that our findings will shed light on the molecular events involved in bone marrow failure syndromes.
Effects of 5-Androstenediol on Survival, Clonogenicity, and Expression of IL-6 and NFKB in Irradiated Human Osteoblast and Hematopoietic CD34+ Cells.
Authors: Xiao Mang , Inal Cynthia E. , Whitnall Mark H. 
Published: October 2019

Abstract
We previously reported that 5-androstenediol (5-AED) administration enhanced survival in mice exposed to whole-body ionizing-radiation (IR). 5-AED also induced hematopoiesis and hematopoietic growth factor expression in blood-forming tissue. Since osteoblasts comprise an important part of the hematopoietic niche, we evaluated the radioprotective effects of 5-AED in a human fetal osteoblast cell line (hFOB) and primary human hematopoietic CD34+ progenitor cells. 5-AED (1000 ng/ml) increased hFOB cell survival from 39% (vehicle-treated) to 85% 3 days after a radiation dose of 2 Gy, and from 56% to 64% after 4 Gy. In clonogenic assays of CD34+ cells starting with 104 cells/dish, BFU-E colonies in 5-AED (1000 ng/ml)-treated cultures increased from 163±17 (vehicle-treated) to 418±20 24 h after 2 Gy, and from 59±5 to 118±11 after 4 Gy. CFU-GM colonies in 5-AED-treated cultures rose from 89±6 to 177±13 after 2 Gy, and from 27±3 to 51±3 cells after 4 Gy. Furthermore, 5-AED administration to irradiated CD34+ cell cultures led to an elevated frequency of CD11b+ cells (granulocytes, monocytes and NK cells) as determined by flow cytometry 22 days after irradiation. To test our hypothesis that 5-AED acts via initiation of a cytokine cascade in hematopoietic cells, endogenous IL-6 protein expression was evaluated using ELISA. Administration of 5-AED before and after IR elicited a 10-fold increase in IL-6 levels in CD34+ cultures 24 h after IR. In contrast, IL-6 levels were not elevated in 5-AED-treated, unirradiated CD34+ cells. Recent studies showed that nuclear factor kappa B (NFkB) may play an important role in IR induced damage. We assessed NFkB activation in human FOB and CD34+ cells and now report for the first time that NFkB subunit NFkB1 (p50) expression was significantly inhibited by IR in CD34+ cells in a dose-dependent manner. Moreover, 5-AED at least partially blocked the downregulation of NFkB1 expression in irradiated cells. Taken together, our results demonstrate that 5-AED counters the effects of IR in human hematopoietic CD34+ and osteoblast cells, and that these effects may be mediated by modulation of IL-6 and NFkB.
Splice Form Specific Signaling of the Hematopoietic Growth Factor Receptor c-Kit.
Authors: Pedersen Malin , Sundberg Christina , Ronnstrand Lars 
Published: October 2019

Abstract
c-Kit is a member of the receptor tyrosine kinase family class III. Upon stimulation with its ligand, stem cell factor, c-Kit becomes activated and phosphorylated on tyrosine residues. The receptor activation leads to cellular responses such as proliferation, differentiation, survival and migration. c-Kit is known to be involved in the pathogenesis of several forms of cancer, e.g. gastrointestinal stroma tumors, leukemias and small-cell lung cancer. c-Kit exists in different isoforms due to alternative mRNA splicing. We are studying one pair of isoforms which varies by the presence or absence of four amino acids GNNK, in the juxtamembrane region just outside the plasma membrane. They are denoted GNNK− and GNNK+, respectively, and have previously been shown by our group to display functional differences in the activation of signaling pathways and cellular responses in the fibroblast cell line NIH3T3. The GNNK− splice form binds and activates Src family kinases more efficiently than the GNNK+ splice form. This leads to stronger phosphorylation of ShcA, extracellular signal regulated kinase 1/2 (Erk) and Cbl compared to the GNNK+ form. In order to study the two GNNK spliceforms in a more physiological context, we have retrovirally transduced two hematopoietic cell lines, 32D and BaF/3, which we now use as our model system. We could demonstrate that SCF stimulation induced a kinetically faster and stronger tyrosine phosphorylation pattern in the GNNK− splice form than the c-Kit GNNK+ splice form. Moreover, the phosphorylation of Erk and Shc is stronger in the c-Kit GNNK− splice form. These results are in line with the results described for NIH3T3 fibroblasts and previously published by our group. We are investigating the SCF-induced proliferative response in the hematopoietic cell lines 32D and BaF/3. Having established these model cell lines, we now aim to use Affymetrix microarray technology to detect differences in gene expression between the two splice forms upon ligand stimulation for different periods of time. As these different splice forms show remarkable differences in their signaling capacity we expect to find significant differences, but also similarities, in gene induction/repression mediated by the c-Kit splice forms. The idea is to link these findings to the biological responses induced by the two splice forms. We will more thoroughly investigate these findings using different c-Kit mutants and a battery of inhibitors of signaling proteins of interest available in the lab. An increased knowledge of c-Kit signaling in general and of the two different c-Kit splice forms in particular will help to find rational treatment for the unfavorable effect of c-Kit in cancer.
Mesenchymal Stem Cells, Fibroblasts and Pericytes: Different Functional States of the Same Cell?.
Authors: Covas Dimas T. , Penepucci Rodrigo A. , Fontes Aparecida M. , Orellana Maristela , Prata Karen L. , Neder Luciano , Perez Luiz C. , Carrara Rita C. , Araujo Amelia G. , Zago Marco A. 
Published: October 2019

Abstract
Mesenchymal stem cells (MSC) are multipotent precursors present in the bone marrow (BM), capable of differentiating into osteoblasts, adipocytes, chondrocytes and myoblasts. In addition to BM, MSC can be obtained from a variety of adult and fetal tissues. Additionally pericytes, that form a continuous subendothelial network of the vascular bed, share many properties with MSC, whereas the name stromal cell or fibroblast is often used interchangeably with MSC. How similar are MSCs obtained from different human tissues and what is their relationship with fibroblasts and pericytes? To answer these questions we have examined the expression of a set of 30 genes in 18 different human cell lines cultured in vitro: 7 MSC cultures from different sources (3 adult tissues: bone marrow, saphena vein, adipose tissue, and 4 fetal tissues: artery, liver, umbilical artery and umbilical vein), 2 of fibroblasts, 2 MSC cultures differentiated in vitro into adipocytes or osteoblasts, and one each of pericytes from the human retina, of bone marrow, endothelial cells, liver, brain, skeletal muscle and heart. Genes were selected on the basis of previous results of SAGE for MSC, CD34+ cells and fibroblasts. Cluster analysis using the software Cluster 3.0 UPGMA (average linkage) showed that all the MSC lines formed a very close cluster with pericytes and fibroblasts, separated from other normal human cells. Changes of the expression of highly expressed MSC genes were modest during in vitro differentiation of MSCs into osteoblasts or adipocytes, although the differentiation was accompanied by the increased expression of tissue specific genes. In addition, all the MSC lines had similar immunophenotypic markers and capacity for in vitro differentiation. Similarity of the gene expression profiles of MSC and fibrobasts were further confirmed by clustering of the 1,000 top expressed tags of SAGE libraries for 21 normal human tissues. Despite the similarity, expression of genes related to angiogenesis, especially CXCL6, was higher in MSC from umbilical vein, adult saphena vein and in pericytes than in BM-derived MSC. In conclusion, MSC that can be obtained from a variety of adult and fetal tissues have very similar biological markers, differentiation potential and gene expression profiles. Comparison of these characteristics also shows that MSC, fibroblasts and pericytes are very closely related, representing probably different functional states of the same cell. Finally, differentiaton of MSC into osteoblasts or adipocytes is marked by the expression of tissue specific genes, without dramatical changes of the overall profile.
Dicentric(7;9)(p11;p11) in Acute Lymphoblastic Leukemia: A Clinical and Laboratory Study of 7 Cases.
Authors: Pan Jin-lan , Xue Yong-quan , Wu Ya-fang , Wang Yong , Shen Juan 
Published: October 2019

Abstract
The clinical and experimental features of 7 cases of acute lymphoblastic leukemia(ALL) with the dicentric chromosome dic(7;9) (p11;p11) were investigated. Five patients were male and two were female. Their median age was 32 years. Cytogenetic examination of bone marrow cells was performed by direct method or 24h culture method. R banding techique was used for karyotype analysis. Among them, dic(7;9) was found to be the sole abnormality in 2 cases, t(9;22) and other additional aberrations were detected besides dic(7;9) in 4 cases as well as dic(7;9) and other abnormalities without t(9;22) were found in one case. Hyperleukocytosis(>100×109/L) was found in 4 cases with dic(7;9) and t(9;22), whereas 3 cases with sole dic(7;9) or dic(7;9) and other abnormalities had a WBC of 1.0–100×109/L. Enlargement of liver, spleen and/or lymph nodes were found in 6 cases. Immunophenotyping analysis showed that 5/6 cases of dic(7;9) ALL were B lineage ALL. Dual-color FISH detected BCR/ABL rearrangment in 3/6 cases and confirmed that the centromere of the derivative chromosome was originated from both chromosomes 7 and 9. A reciprocal translocation between chromosomes 7 and 9 was proved by chromosome patinting technique using whole chromosome paint probes for both chromosomes 7 and 9. This study has increased the number of reported cases of dic(7;9) from 8 to 15. Thus, we consider that dic(7;9) was a rare, but recurrent chromosome abnormality in ALL. It may appear as a primary change but also as secondary one following t(9;22), and had unique clinical and laboratory features.