bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relationship between Circulating Microparticles and Complications of Pregnancy.
Authors: Salomon Ophira , Dardik Rima , Katz Ben-Zion , Steinberg David M. , Achiron Reuven , Seligsohn Uri 
Published: October 2019

Abstract
Uteroplacental thrombosis has been implicated in the pathogenesis of fetal loss, intrauterine growth restriction (IUGR) and preeclampsia. The role of inherited and acquired thrombophilias in such pregnancy complications is controversial. Recently, increased levels of circulating procoagulant microparticles (MPs) were related to fetal loss and preeclampsia (Laude et al. Thromb Haemost2001;85:18, Gonzalez-Quintero et al. Am J Obstet Gynecol2004;191:1418)). In this study, we measured the level of MPs derived from endothelial cells, platelets, and monocytes by flow cytometry using monoclonal antibodies against CD31, CD41 and CD14, respectively in 262 healthy unrelated primipara with a spontaneous singleton pregnancy. Expression of tissue factor by a monoclonal antibody and phosphatidyl serine by annexin 5 on MPs were also measured. All women were followed from the 24th week of gestation until delivery and IUGR, small for gestational age (SGA) at birth, pregnancy induced hypertension (PIH) or preeclampsia (PE) or none of the above were recorded. Blood sampling was carried out at 24th week of gestation. The levels of CD31 and CD41- positive MPs in women with and without the above pregnancy complications are presented in the table. Not shown are values of CD14, annexin 5 or tissue factor on MPs since their median levels were negligible in all study groups. There was no statistically significant difference in CD31 and CD41- positive MPs between women who developed or not the indicated pregnancy complications. Also, there was no significant difference in levels of these MPs between women with and without the common inherited thrombophilias, factor V Leiden and or prothrombin mutation (28 patients) and lupus anticoagulant (10 patients). These data indicate that measurement of the level of MP at the 24th week of gestation has no predictive value for development of PIH, PE, IUGR or SGA.
CD31 CD41 Number Median % p Median % p PIH or PE No 226 1.50 0.22 1.80 PIH Yes 13 1.57 3.07 0.53 PE Yes 22 0.62 1.87 IUGR No 207 1.53 0.13 1.95 0.08 IUGR Yes 32 1.30 1.71 SGA No 232 1.48 0.64 1.85 0.81 SGA Yes 26 1.27 2.24
Acceptibility of Patient Self-Testing of Oral Anticoagulation in New Patients.
Authors: Pescott Marie A. , Longair Ian , Gardiner Chris , Austin Steven K. , Machin Samuel J. 
Published: October 2019

Abstract
Monitoring oral anticoagulation therapy (OAT) remains a significant burden on health care resources. Patient self-testing (PST) of OAT using point of care devices may alleviate these demands and improve the quality of treatment. Previous studies have shown limited benefit, as recruitment amongst patients previously established on OAT has proven to be difficult with only around 10–15 % of those invited agreeing to participate, suggesting that PST may only be suitable for a minority of patients. We aimed to assess whether PST is more acceptable to patients if offered at the commencement of treatment. 216 consecutive adults referred to anticoagulation clinics were assessed for their suitability for PST. Exclusion criteria included: short therapeutic duration (e.g. pre-cardioversion); known drug/alcohol abuse; atypical INR target values; language barriers; physical/intellectual impairment. Suitable patients were offered the opportunity to perform PST with 2 training sessions and thereafter monitor their INR every 1–2 weeks using CoaguChek S (Roche Diagnostics). It was noted during recruitment of the first 100 patients, that patients awaiting cardioversion accounted for a large proportion of the patients excluded (15/54, 28%), but many patients awaiting cardioversion received OAT in excess of six months. We therefore modified initial entry criteria, to include those with atrial fibrillation awaiting cardioversion. Of the 116 patients subsequently approached 37 (32%) were then recruited to PST (compared with only 17 cardiac patients from the first 100 enrolled into the study). 98 (45%) patients fulfilled our entry criteria for PST, of whom 54 (25%) consented to PST. Of the 118 ineligible patients: 23 had previously received OAT; 15 were awaiting cardioversion; the expected duration of OAT was less than 6 months in 13 patients; and PST was logistically impractical in 32 other patients. A further 35 were excluded for a wide variety of reasons including non-standard INR ranges, language barriers, discontinuation of OAT and planned surgical procedures. Only two of the 54 patients who started PST elected to return to hospital testing. Overall 53 % (52/98) of eligible patients have continued to self-test. The INR values obtained from these patients showed that their oral anticoagulant control remained stable (mean time in therapeutic range of 71%), and compared favourably to those patients electing to attend our routine anticoagulant clinic. Our data show that patients offered PST as an alternative to routine clinic management during induction of anticoagulation were more likely to participate in PST than established patients. Furthermore, the vast majority of patients (96%) continued to self-test, a higher figure than previous studies involving established patients.
Genomic Distribution of Transcripts and DNA Associated Proteins in One Percent of the Genome of Erythroid and Myeloid Cells.
Authors: Lian Jin , Lian Zheng , Karpikov Alexander , Mahajan Milind , Gerstein Mark , Snyde Michael , Weissman Sherman 
Published: October 2019

Abstract
The NIHGRI has sponsored a multi-group enterprise to use a variety of approaches to map DNA elements in one per cent of the human genome-the ENCODE Project. As part of this effort we have mapped sites of active transcription (transcriptionally active regions or TARS) for myeloid cells including the undifferentiated and retinoic acid treated promyelocytic NB4 cell line and normal neutrophils, as well as the erythroid cell line K562. The results show a large number of intergenic and intronic transcripts, particularly in neutrophils. One feature of note is the amount of cell type specific intergenic transcription in the HoxA cluster. In addition we have been developing simple methods to map the sites of polyadenylation of RNAs and applied this to several cell types. This method also indicates the presence of polyadenylated transcripts derived from the multiple introns of known genes as well as intergenic regions.
In parallel with the transcript mapping, we have been performing microarray based chromatin immunoprecipitation studies (Chip-chip) on several factors, analyzing them on oligonucleotide arrays tiling the ENCODE selected genomic regions. These include various phosphorylated forms of RNA polymerase, various methylated forms of histone H3, certain DNA sequence specific transcription factors, and some other factors either broadly involved in chromatin remodeling or specifically found to be associated with certain sequences in the beta globin cluster. Among other things, our results as well as those of other members of the ENCODE consortium, provide a signature motif commonly associated with promoters.
The Expression and Clinical Significance of FLT3/ITD Gene Mutation in Different Hematologic Malignancy.
Authors: Xu Bing , Tang Jia-hong , Li Lin 
Published: October 2019

Abstract
Objective To analyze Fms-like tyrosine kinase 3 (FLT3) gene internal- tandem duplications(ITD) mutation in various kinds of hematologic malignancy. Methods Polymerase chain reaction(PCR)was used to detect FLT3/ITD gene mutation in 103 AML cases, 63 ALL cases, 53 CML in chronic phase(CML-CP), 34 CML cases in blast crisis(CML-BC), 11 CLL cases, 36 MDS cases, 9 MM cases and 13 NHL cases with marrow infiltration. Results The mutation of FLT3/ITD gene was detected in 22.3% AML cases, in 6.5% CML -BC cases, in 5.6% MDS cases and in 2.6% ALL cases, This two ALL cases with FLT3/ITD mutation were both with myeloid antigen expression and were diagnosed as acute mixed-lineage leukemia after immunology examination. FLT3/ITD gene mutation were not detected in CML-CP, MM, NHL and CLL cases. FLT3/ITD+ AML shew high white blood cell count and high percentage of bone marrow blast cells and had a unfavourable cumulative relapse rates. Conclusion FLT3/ITD gene mutation was majority in AML cases and FLT3/ITD+ AML had a poor prognosis. Detection of FLT3/ITD gene mutation may be valuable in genotyping of leukemia, differential diagnosis between AML and ALL and estimate the prognosis of leukemia.
E6-Associated Protein (E6-AP): A Potential Tumor Suppressor Protein for Non-Hodgkin Lymphoma.
Authors: Zafar Shazia , Srinivasan Sathish , Nawaz Zafar 
Published: October 2019

Abstract
Over the past decade considerable progress has been made in cloning and characterization of potential tumor suppressor genes. Tumor suppressors have a repressive effect on the regulation of the cell cycle or promote apoptosis and sometimes do both. The function of tumor suppressor proteins fall into several categories, tumor suppressor genes are presumed to encode negative regulator of proliferation and inhibit mitotic activity. Loss of tumor suppressor protein or function of a tumor suppressor protein has been shown to be associated with the cancer formation. Continued investigation into the biochemical and cell biological functions of the tumor suppressor is critical to elucidate the mechanisms by which they normally inhibit proliferation/tumor development and to provide a molecular explanation for their frequent inactivation in cancer. Our laboratory has previously shown that the expression of E6-associated protein (E6-AP), which is an E3 ubiquitin-protein ligase and a coactivator of nuclear hormone receptors, is significantly reduced in human cancers having epithelial cell origin such as breast cancer. In this prospective study, we want to extend our observation to the cancers originating from lymphoid tissue. Non-Hodgkin lymphoma is a cancer of lymphoid tissue. The main cell type found in lymphoid tissue is the lymphocyte. The 2 main types of lymphocytes are B-lymphocytes (B-cells) and T-lymphocytes (T-cells). B-cell lymphomas are much more common than T-cell lymphomas. In the U. S., 85% of all cases of non-Hodgkin lymphoma come from B lymphocytes (B-cell) and 15% from T lymphocytes (T-cell). We performed immunohistochemistry analysis to investigate the expression pattern of E6-AP in normal lymph nodes and lymphoid tumors. Tissue micro arrays representing samples from 60 different patients were analyzed in this study. Our analysis suggest that on an average there was about 55 % reduction in E6-AP protein levels in B-cell lymphomas (P =0.0001) and 98.5 % reduction in E6-AP levels in T-cell lymphomas (P =0.0002) compared to normal lymph node. Based on our previous studies in breast and prostate tumors and considering our current finding of reduced/loss of E6-AP in lymphoid tumors, we propose that E6-AP may act as a potential tumor suppressor protein. This proposed idea is consistent with our in vivo data generated from E6-AP null mice which shows that the number of B- and T-cells are significantly increased in spleen compared to normal wild-type animals. Taken together our data establish the role of E6-AP as a potential growth and tumor suppressor protein.
The Four and a Half LIM Domain Protein 2 (FHL2) Interacts with CALM and Is Highly Expressed in AML with Complex Aberrant Karyotpes.
Authors: Pasalic Zlatana , Tizazu Belay , Archangelo Leticia , Krause Alexandre , Philipp Greif , Bohlander Stefan K. 
Published: October 2019

Abstract
The balanced chromosomal translocation t(10;11)(p13;q14) results in the CALM/AF10 fusion gene. This translocation is found in acute myeloid leukemia (AML), T-cell acute lymphoblastic leukaemia (T-ALL) and malignant lymphoma. The CALM/AF10 fusion gene has recently been shown to cause an aggressive biphenotypic leukemia in a murine bone marrow transplant model. The CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) gene product is a clathrin assembly protein which plays a role in clathrin mediated endocytosis and trans Golgi network trafficking. AF10 is a putative transcription factor most likely involved in processes related to chromatin organization and has polycomb group gene like properties.
To learn more about the function of the CALM/AF10 fusion protein, we searched for protein interaction partners of CALM. In a yeast two hybrid screen the four and a half LIM domain protein FHL2 was identified as putative CALM interacting partner. The CALM FHL2 interaction was confirmed by co-transformation assay in yeast and by GST-pulldown experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294 to 335 of CALM using the yeast two hybrid assay. In co-localization studies with transiently expressed fluorescent protein tagged CALM and FHL2, both proteins showed cytoplasmatic localization. Expression analysis (Affymetrix based) in different AML subtypes showed a significantly higher expression of FHL2 in AML with complex aberrant karyotypes compared to AML with normal karyotypes or balanced chromosomal translocations like the t(8;21), inv(16) or t(15;17).
FHL2, which is also known as DRAL (downregulated in rhabdomyosarcoma LIM protein), is a TP53 responsive gene known to interact with numerous proteins in both the nucleus and the cytoplasm and can function as a transcriptional cofactor. Known FHL2 interactors include TP53, BRCA1, PLZF (promyelocytic leukemia zinc finger protein), the proto-oncogene SKI1 and beta-catenin. High expression of FHL2 in breast cancer has recently been shown to be associated with an adverse prognosis. CALM has been shown to shuttle between the nucleus and the cytoplasm because inhibition of CREM-mediated nuclear export by leptomycin B leads to the accumulation of CALM in the nucleus. Reporter gene assays using a GAL4-DNA binding domain CALM fusion protein and a GAL4 responsive luciferase reporter were able to demonstrate a transcriptional activation function of CALM. We are currently investigation the effect of FHL2 co-expression on this aspect of the CALM function.
It is thus conceivable that FHL2 is playing an important role in CALM/AF10-mediated leukemogenesis by tethering the CALM/AF10 fusion protein to various nuclear transcription factor complexes.
Identification of Peptide Epoxy-Ketone Proteasome Inhibitors with Differential Active Site Selectivity.
Authors: Demo Susan D. , Aujay Monette A. , Goldstein Eileen , Laidig Guy J. , Parlati Francesco , Lu Yan , Shenk Kevin D. , Sun Congcong M. , Sylvain Catherine , Woo Tina M. , Zhou Hanjie , Bennett Mark K. 
Published: October 2019

Abstract
The proteasome is a multi-subunit structure responsible for degrading the majority of proteins in the cell. The three catalytic subunits in the 20S core of the proteasome are defined by their preference for amino acid side chains at the P1 position: the beta5 subunit (chymotrypsin-like), the beta2 subunit (trypsin-like), and the beta1 subunit (caspase-like) hydrolyze substrates after hydrophobic, basic, and acidic residues, respectively. Bortezomib (Velcade®), currently an approved drug for the treatment of multiple myeloma, is a potent inhibitor of the beta5 subunit but also has activity against the beta1 subunit (9-fold less active) and the beta2 subunit (250-fold less active). PR-171, a peptide epoxy-ketone proteasome inhibitor currently in Phase I clinical trials in multiple myeloma and NHL patients, has a distinct profile of inhibition. Similar to bortezomib, PR-171 is most potent against the beta5 subunit, but differs in its activity against the beta2 and beta1 subunits (45-fold less active and 140-fold less active, respectively). Although both bortezomib and PR-171 are cytotoxic to a variety of tumor cell types, the connection between inhibition of specific proteasomal subunits and cellular consequences, including induction of apoptosis, is currently unclear. To investigate this relationship, we synthesized a series of PR-171 analogs and profiled them in our proteasome-specific active site ELISA binding assay to identify compounds with differential binding profiles for the three catalytic subunits. Using this approach, we have identified compounds that bind all three catalytic sites with approximately equivalent activity as well as compounds that have increased specificity for the beta5 subunit. We have extended this approach to search for compounds with differential binding profiles for the immunoproteasome catalytic subunits. The immunoproteasome is the predominant form of the proteasome expressed in cells of hematopoetic origin and in other cell types after interferon-g stimulation. In the 20S core of the immunoproteasome the beta5, beta2 and beta1 subunits of the “constitutive” proteasome are replaced by the homologous subunits LMP7, MECL1, and LMP2. We have successfully identified inhibitors with distinct active site profiles for the immunoproteasome as well as the constitutive proteasome. The impact of differential active site inhibition on tumor cell viability is under investigation in a variety of solid and hematological tumor cell lines expressing the constitutive proteasome or the immunoproteasome.
Immunogenicity of Influenza Vaccination in Patients with Non-Hodgkin Lymphoma: Final Report after Two Epidemic Seasons.
Authors: Centkowski Piotr , Brydak Lidia B. , Machala Magdalena , Kalinka Ewa , Blasinska-Morawiec Maria , Federowicz Irena , Walewski Jan , Wegrzyn Joanna , Wolowiec Dariusz , Maranda Ewa , Sawczuk-Chabin Joanna , Bilinski Przemyslaw , Warzocha Krzysztof 
Published: October 2019

Abstract
Vaccination against influenza is recommended for immunocompromised individuals. However, there is little information concerning the efficacy of vaccination in patients (pts) with non-Hodgkin lymphoma (NHL). The purpose of this study was to assess humoral response to standard intramuscular trivalent subunit influenza vaccine in pts with NHL as compared to healthy subjects. In two consecutive epidemic seasons, 2003/2004 and 2004/2005, 163 pts and 92 healthy controls were vaccinated. Antibody titers to hemagglutinin (HA) and neuraminidase (NA) were measured in serum samples collected before vaccination, and 1 and 6 months apart. Changes in the hemagglutination inhibition (HAI) and neuraminidase inhibition (NII) antibody titers were assessed by comparing geometric mean titers and mean fold increases to baseline values and by comparing changes in the HA seroconversion and seroprotection rates. Pts who received influenza vaccine during 2003/2004 season had after one month increases in the geometric mean titers by a factor of 8,64–26,60 for HI and 6,93–12,66 for NI, as compared with respective increases by a factor of 9,12–24,41 and 4,83–10,31 for the healthy controls. At one month after vaccination seroprotection and seroresponse rates were similar in the two groups, ranging from 68,42 to 84,21 % and 71,93 to 94,74 % in NHL and 66,67–82,22 % and 62,22–86,67 % in controls, respectively. After six months, seroprotection and seroresponse rates had decreased in NHL group to 31,91–38,30% and 46,81–72,34%, respectively. Pts who received influenza vaccine during 2004/2005 season had after 1 month increases in the geometric mean titers by a factor of 38,76–41,49 for HI and 26,59–30,31 for NI, as compared with respective increases by a factor of 81,19–104,32 and 52,16–54,52 for the healthy controls. Seroprotection and seroresponse rates were lower in the former group, ranging from 62,11 to 65,26 % and 74,47 to 77,66 %, respectively. After six months, these parameters had decreased to 24,72–31,46% and 57,30–59,55%, respectively. In both studied seasons, pts achieved titres of functional antibodies greater than the protective threshold, irrespective of the previous chemotherapy administration. The results of this study indicate that standard influenza vaccination induces sufficient immune responses in pts with NHL. Previous chemotherapy adminstration seems to have no impact on the efficacy of vaccination.
RNA Interference Against Bcl-2 mRNA Increases Radiosensitivity of Raji Cells.
Authors: He Dongmei , Zhang Yuan , Liu Gexiu 
Published: October 2019

Abstract
Bcl-2 is the prominent member of a family of proteins responsible for dysregulation of apoptosis, and resistance to chemotherapy. It has been shown that reduction in Bcl-2 protein levels could ultimately induce a lower apoptotic threshold and restore chemosensitivity in a variety of malignancies. Short interfering RNA (siRNA) has been evaluated as an attractive and effective tool for suppressing a target protein by specifically digesting its mRNA. In our lab, we have identified a siRNA targeting against Bcl-2 could effectively down-regulate Bcl-2 protein. In this study, we investigated the effect of gamma radiation combined with the siRNA targeting Bcl-2 on proliferation and apoptosis in B-lymphoma Raji cells. The siRNA was introduced into cells using Oligofectamine transfection. Cells were treated with Bcl-2 siRNA alone or with 2–8 Gy dose of (60)Co gamma rays. Expression of Bcl-2 mRNA and protein was assayed by quantitative reverse transcriptase-polymerase chain reaction and Western blotting analysis. Radiosensitivity was determined by clonogenic cell survival assay. Apoptosis was determined by Giemsa staining, Annexin-V binding assay and flow cytomertry. Furthermore caspase-3 activity and poly (ADP-ribose) polymerase (PARP) cleavage were evaluated. Transfection of Raji cells with 100 nmol/L siRNA targeted against Bcl-2 resulted in reduction of Bcl-2 mRNA by 75% compared with control-siRNA treated group and the vehicle control group(p<0.05). The levels of Bcl-2 protein were significantly reduced by 70% compared with the two control groups (p<0.05). There was significant difference in the radiosensitivity of Raji cells in which Bcl-2 was silenced compared with the cells transfected vehicle or control siRNA.Apoptosis index of the Raji cells treated with Bcl-2 siRNA combined with radiation was significantly increased (p<0.05), compared with either control siRNA / radiation combination or radiation-treatment cells alone, or Bcl-2 siRNA-treatment cells alone.Raji cells treated with Bcl-2 siRNA combined with radiation revealed enhanced caspase-3 and PARP cleavage as compared to Bcl-2 siRNA treated cells alone or only irradiated cells. These findings show that Bcl-2 siRNA synergistically enhances radiation-induced apoptosis through the expression of proteins involved in the programmed cell death.