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[PMID]: 25238757
[Au] Autor:Park KS; Bayles I; Szlachta-McGinn A; Paul J; Boiko J; Santos P; Liu J; Wang Z; Borghesi L; Milcarek C
[Ad] Address:Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261; and....
[Ti] Title:Transcription Elongation Factor ELL2 Drives Ig Secretory-Specific mRNA Production and the Unfolded Protein Response.
[So] Source:J Immunol;193(9):4663-74, 2014 Nov 1.
[Is] ISSN:1550-6606
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Differentiation of B cells into Ab-secreting cells induces changes in gene transcription, IgH RNA processing, the unfolded protein response (UPR), and cell architecture. The transcription elongation factor eleven nineteen lysine-rich leukemia gene (ELL2) stimulates the processing of the secreted form of the IgH mRNA from the H chain gene. Mice (mus musculus) with the ELL2 gene floxed in either exon 1 or exon 3 were constructed and crossed to CD19-driven cre/CD19(+). The B cell-specific ELL2 conditional knockouts (cKOs; ell2(loxp/loxp) CD19(cre/+)) exhibit curtailed humoral responses both in 4-hydroxy-3-nitrophenyl acetyl-Ficoll and in 4-hydroxy-3-nitrophenyl acetyl-keyhole limpet hemocyanin immunized animals; recall responses were also diminished. The number of immature and recirculating B cells in the bone marrow is increased in the cKOs, whereas plasma cells in spleen are reduced relative to control animals. There are fewer IgG1 Ab-producing cells in the bone marrow of cKOs. LPS ex vivo-stimulated B220(lo)CD138(+) cells from ELL2-deficient mouse spleens are 4-fold less abundant than from control splenic B cells; have a paucity of secreted IgH; and have distended, abnormal-appearing endoplasmic reticulum. IRE1α is efficiently phosphorylated, but the amounts of Ig κ, ATF6, BiP, Cyclin B2, OcaB (BOB1, Pou2af1), and XBP1 mRNAs, unspliced and spliced, are severely reduced in ELL2-deficient cells. ELL2 enhances the expression of BCMA (also known as Tnfrsf17), which is important for long-term survival. Transcription yields from the cyclin B2 and the canonical UPR promoter elements are upregulated by ELL2 cDNA. Thus, ELL2 is important for many aspects of Ab secretion, XBP1 expression, and the UPR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.4049/jimmunol.1401608

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[PMID]: 25238756
[Au] Autor:Li J; Kurasawa Y; Wang Y; Clise-Dwyer K; Klumpp SA; Liang H; Tailor RC; Raymond AC; Estrov Z; Brandt SJ; Davis RE; Zweidler-McKay P; Amin HM; Nagarajan L
[Ad] Address:Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030;...
[Ti] Title:Requirement for ssbp2 in hematopoietic stem cell maintenance and stress response.
[So] Source:J Immunol;193(9):4654-62, 2014 Nov 1.
[Is] ISSN:1550-6606
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Transcriptional mechanisms governing hematopoietic stem cell (HSC) quiescence, self-renewal, and differentiation are not fully understood. Sequence-specific ssDNA-binding protein 2 (SSBP2) is a candidate acute myelogenous leukemia (AML) suppressor gene located at chromosome 5q14. SSBP2 binds the transcriptional adaptor protein Lim domain-binding protein 1 (LDB1) and enhances LDB1 stability to regulate gene expression. Notably, Ldb1 is essential for HSC specification during early development and maintenance in adults. We previously reported shortened lifespan and greater susceptibility to B cell lymphomas and carcinomas in Ssbp2(-/-) mice. However, whether Ssbp2 plays a regulatory role in normal HSC function and leukemogenesis is unknown. In this study, we provide several lines of evidence to demonstrate a requirement for Ssbp2 in the function and transcriptional program of hematopoietic stem and progenitor cells (HSPCs) in vivo. We found that hematopoietic tissues were hypoplastic in Ssbp2(-/-) mice, and the frequency of lymphoid-primed multipotent progenitor cells in bone marrow was reduced. Other significant features of these mice were delayed recovery from 5-fluorouracil treatment and diminished multilineage reconstitution in lethally irradiated bone marrow recipients. Dramatic reduction of Notch1 transcripts and increased expression of transcripts encoding the transcription factor E2a and its downstream target Cdkn1a also distinguished Ssbp2(-/-) HSPCs from wild-type HSPCs. Finally, a tendency toward coordinated expression of SSBP2 and the AML suppressor NOTCH1 in a subset of the Cancer Genome Atlas AML cases suggested a role for SSBP2 in AML pathogenesis. Collectively, our results uncovered a critical regulatory function for SSBP2 in HSPC gene expression and function.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.4049/jimmunol.1300337

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[PMID]: 24658222
[Au] Autor:Stabley JN; Moningka NC; Behnke BJ; Delp MD
[Ad] Address:1Center for Exercise Science, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL; and 2Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL.
[Ti] Title:Exercise Training Augments Regional Bone and Marrow Blood Flow during Exercise.
[So] Source:Med Sci Sports Exerc;46(11):2107-12, 2014 Nov.
[Is] ISSN:1530-0315
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:INTRODUCTION: The principal nutrient artery to the femur demonstrates an increase in nitric oxide-mediated vasodilation in rats after treadmill exercise training. The present study sought to determine whether exercise training improves hindlimb bone and marrow blood flow distribution at rest and during exercise. METHODS: Six 8-month old male Sprague-Dawley rats were exercise trained (ET) with treadmill walking at 15 m·min up a 15° incline for 60 min·d over a 10- to 12-wk period. Sedentary (SED) control animals were acclimated to treadmill exercise for 5 min·d during the week preceding the blood flow measurements. Blood flow to nine distinct regions of the femur, tibia, and fibula was determined at rest and during low-intensity exercise (15 m·min walking, 0° incline) using the reference sample microsphere method. RESULTS: The results demonstrate an augmentation of exercise hyperemia above that observed in SED rats during exercise in only one region of the bone, the femoral diaphysis, of ET rats. However, whereas exercise hyperemia occurred in three of the nine hindlimb bone regions measured in SED rats, exercise hyperemia occurred in seven of nine regions in ET rats. CONCLUSIONS: These data indicate an increase in generalized hindlimb bone and marrow blood flow during physical activity after a period of exercise training. Elevations in regional bone and marrow blood flow after training may augment medullary pressure and bone interstitial fluid flow, thus benefiting bone integrity.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1249/MSS.0000000000000342

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[PMID]: 25323256
[Au] Autor:Kim SW; Houge M; Brown M; Davis ME; Yoon YS
[Ad] Address:Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia; Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Incheon, South Korea; International St. Mary's Hospital, Incheon, South Korea; Department of Anatomy and Ce...
[Ti] Title:Cultured Human Bone Marrow-Derived CD31(+) Cells Are Effective for Cardiac and Vascular Repair Through Enhanced Angiogenic, Adhesion, and Anti-Inflammatory Effects.
[So] Source:J Am Coll Cardiol;64(16):1681-94, 2014 Oct 21.
[Is] ISSN:1558-3597
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Cell therapy for cardiovascular disease has been limited by low engraftment of administered cells and modest therapeutic effects. Bone marrow (BM) -derived CD31(+) cells are a promising cell source owing to their high angiovasculogenic and paracrine activities. OBJECTIVES: This study sought to identify culture conditions that could augment the cell adhesion, angiogenic, and anti-inflammatory activities of BM-derived CD31(+) cells, and to determine whether these cultured CD31(+) cells are effective for cardiac and vascular repair. METHODS: CD31(+) cells were isolated from human BM by magnetic-activated cell sorting and cultured for 10 days under hematopoietic stem cell, mesenchymal stem cell, or endothelial cell culture conditions. These cells were characterized by adhesion, angiogenesis, and inflammatory assays. The best of the cultured cells were implanted into myocardial infarction (MI) and hindlimb ischemia (HLI) models to determine therapeutic effects and underlying mechanisms. RESULTS: The CD31(+) cells cultured in endothelial cell medium (EC-CD31(+) cells) showed the highest adhesion and angiogenic activities and lowest inflammatory properties in vitro compared with uncultured or other cultured CD31(+) cells. When implanted into mouse MI or HLI models, EC-CD31(+) cells improved cardiac function and repaired limb ischemia to a greater extent than uncultured CD31(+) cells. Histologically, injected EC-CD31(+) cells exhibited higher retention, neovascularization, and cardiomyocyte proliferation. Importantly, cell retention and endothelial transdifferentiation was sustained up to 1 year. CONCLUSIONS: Short-term cultured EC-CD31(+) cells have higher cell engraftment, vessel-formation, cardiomyocyte proliferation, and anti-inflammatory potential, are highly effective for both cardiac and peripheral vascular repair, and enhance survival of mice with heart failure. These cultured CD31(+) cells may be a promising source for treating ischemic cardiovascular diseases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review

  5 / 312476 MEDLINE  
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[PMID]: 25320545
[Au] Autor:Pan XN; Zheng LQ; Lai XH
[Ad] Address:Xing-Nan Pan, Lian-Qiu Zheng, Xiao-Huan Lai, Clinical Liver Center, 180 Hospital of People's Liberation Army, Quanzhou 362000, Fujian Province, China.
[Ti] Title:Bone marrow-derived mesenchymal stem cell therapy for decompensated liver cirrhosis: A meta-analysis.
[So] Source:World J Gastroenterol;20(38):14051-7, 2014 Oct 14.
[Is] ISSN:2219-2840
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:AIM: To assess the efficacy and safety of bone marrow-derived mesenchymal stem cell (BM-MSC) in the treatment of decompensated liver cirrhosis. METHODS: The search terms "bone marrow stem cell" "chronic liver disease" "transfusion" and "injection" were used in the Cochrane Library, Med-Line (Pub-Med) and Embase without any limitations with respect to publication date or language. Journals were also hand-searched and experts in the field were contacted. The studies which used BM-MSC in the treatment of any chronic liver disease were included. Comprehensive Review Manager and Meta-Analyst software were used for statistical analysis. Publication bias was evaluated using Begg's test. RESULTS: Out of 78 studies identified, five studies were included in the final analysis. The studies were conducted in China, Iran, Egypt and Brazil. Analysis of pooled data of two controlled studies by Review Manager showed that the mean decline in scores for the model for end-stage liver disease (MELD) was -1.23 [95%CI: -2.45-(-0.01)], -1.87 [95%CI: -3.16-(-0.58)], -2.01 [95%CI: -3.35-(-0.68)] at 2, 4 and 24 wk, respectively after transfusion. Meta-analysis of the 5 studies showed that the mean improvement in albumin levels was -0.28, 2.60, 5.28, 4.39 g/L at the end of 8, 16, 24, and 48 wk, respectively, after transfusion. MELD scores, alanine aminotransferase, total bilirubin levels and prothrombin times improved to some extent. BM-MSC injections resulted in no serious adverse events or complications. CONCLUSION: BM-MSC infusion in the treatment of decompensated liver cirrhosis improved liver function. At the end of year 1, there were no serious side effects or complications.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3748/wjg.v20.i38.14051

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[PMID]: 25320692
[Au] Autor:Thandassery RB; Sharma M; Abdelmola A; Derbala MF; Al Kaabi SR
[Ad] Address:Department of Gastroenterology and Hepatology, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar....
[Ti] Title:Uncommon gastrointestinal complications of enteric fever in a non-endemic country.
[So] Source:Qatar Med J;2014(1):46-9, 2014.
[Is] ISSN:0253-8253
[Cp] Country of publication:Qatar
[La] Language:eng
[Ab] Abstract:Enteric fever is a systemic illness with varying presentation. It is an important infectious disease in developing countries and also in industrialized countries where many migrants reside. Enteric fever can result in complications in different organ systems and delay in identification and prompt treatment can be fatal. The important gastrointestinal complications of enteric fever include hepatitis, intestinal ulcers, bleeding and bowel perforation. We report three relatively uncommon complications of enteric fever in Qatar, a non-endemic country, ileal ulcer presenting with hematochezia; duodenal ulcer with polyserositis, cholestatic hepatitis and bone marrow suppression; enteric fever related peritonitis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Cu] Class update date: 141018
[Lr] Last revision date:141018
[Da] Date of entry for processing:141016
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.5339/qmj.2014.7

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[PMID]: 25261237
[Au] Autor:Balkin ER; Kenoyer A; Orozco JJ; Hernandez A; Shadman M; Fisher DR; Green DJ; Hylarides MD; Press OW; Wilbur DS; Pagel JM
[Ad] Address:Radiation Oncology, University of Washington, Seattle, Washington....
[Ti] Title:In Vivo Localization of 90Y and 177Lu Radioimmunoconjugates Using Cerenkov Luminescence Imaging in a Disseminated Murine Leukemia Model.
[So] Source:Cancer Res;74(20):5846-54, 2014 Oct 15.
[Is] ISSN:1538-7445
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Cerenkov radiation generated by positron-emitting radionuclides can be exploited for a molecular imaging technique known as Cerenkov luminescence imaging (CLI). Data have been limited, however, on the use of medium- to high-energy ß-emitting radionuclides of interest for cancer imaging and treatment. We assessed the use of CLI as an adjunct to determine localization of radioimmunoconjugates to hematolymphoid tissues. Radiolabeled (177)Lu- or (90)Y-anti-CD45 antibody (Ab; DOTA-30F11) was administered by tail vein injection to athymic mice bearing disseminated murine myeloid leukemia, with CLI images acquired at times afterward. Gamma counting of individual organs showed preferential uptake in CD45(+) tissues with significant retention of radiolabeled Ab in sites of leukemia (spleen and bone marrow). This result was confirmed in CLI images with 1.35 × 10(5) ± 2.2 × 10(4) p/s/cm(2)/sr and 3.45 × 10(3) ± 7.0 × 10(2) p/s/cm(2)/sr for (90)Y-DOTA-30F11 and (177)Lu-DOTA-30F11, respectively, compared with undetectable signal for both radionuclides using the nonbinding control Ab. Results showed that CLI allows for in vivo visualization of localized ß-emissions. Pixel intensity variability resulted from differences in absorbed doses of the associated energies of the ß-emitting radionuclide. Overall, our findings offer a preclinical proof of concept for the use of CLI techniques in tandem with currently available clinical diagnostic tools. Cancer Res; 74(20); 5846-54. ©2014 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/0008-5472.CAN-14-0764

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[PMID]: 25164013
[Au] Autor:Parker KH; Sinha P; Horn LA; Clements VK; Yang H; Li J; Tracey KJ; Ostrand-Rosenberg S
[Ad] Address:Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland....
[Ti] Title:HMGB1 Enhances Immune Suppression by Facilitating the Differentiation and Suppressive Activity of Myeloid-Derived Suppressor Cells.
[So] Source:Cancer Res;74(20):5723-33, 2014 Oct 15.
[Is] ISSN:1538-7445
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Chronic inflammation often precedes malignant transformation and later drives tumor progression. Likewise, subversion of the immune system plays a role in tumor progression, with tumoral immune escape now well recognized as a crucial hallmark of cancer. Myeloid-derived suppressor cells (MDSC) are elevated in most individuals with cancer, where their accumulation and suppressive activity are driven by inflammation. Thus, MDSCs may define an element of the pathogenic inflammatory processes that drives immune escape. The secreted alarmin HMGB1 is a proinflammatory partner, inducer, and chaperone for many proinflammatory molecules that MDSCs develop. Therefore, in this study, we examined HMGB1 as a potential regulator of MDSCs. In murine tumor systems, HMGB1 was ubiquitous in the tumor microenvironment, activating the NF-κB signal transduction pathway in MDSCs and regulating their quantity and quality. We found that HMGB1 promotes the development of MDSCs from bone marrow progenitor cells, contributing to their ability to suppress antigen-driven activation of CD4(+) and CD8(+) T cells. Furthermore, HMGB1 increased MDSC-mediated production of IL-10, enhanced crosstalk between MDSCs and macrophages, and facilitated the ability of MDSCs to downregulate expression of the T-cell homing receptor L-selectin. Overall, our results revealed a pivotal role for HMGB1 in the development and cancerous contributions of MDSCs. Cancer Res; 74(20); 5723-33. ©2014 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/0008-5472.CAN-13-2347

  9 / 312476 MEDLINE  
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[PMID]: 25313644
[Au] Autor:Cardelli M; Aubin JE
[Ad] Address:Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
[Ti] Title:ERRγ Is Not Required for Skeletal Development but Is a RUNX2-Dependent Negative Regulator of Postnatal Bone Formation in Male Mice.
[So] Source:PLoS One;9(10):e109592, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:To assess the effects of the orphan nuclear Estrogen receptor-related receptor gamma (ERRγ) deficiency on skeletal development and bone turnover, we utilized an ERRγ global knockout mouse line. While we observed no gross morphological anomalies or difference in skeletal length in newborn mice, by 8 weeks of age ERRγ +/- males but not females exhibited increased trabecular bone, which was further increased by 14 weeks. The increase in trabecular bone was due to an increase in active osteoblasts on the bone surface, without detectable alterations in osteoclast number or activity. Consistent with the histomorphometric results, we observed an increase in gene expression of the bone formation markers alkaline phosphatase (Alp) and bone sialoprotein (Bsp) in bone and increase in serum ALP, but no change in the osteoclast regulators receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) or the resorption marker carboxy-terminal collagen crosslinks (CTX). More colony forming units-alkaline phosphatase and -osteoblast (CFU-ALP, CFU-O respectively) but not CFU-fibroblast (CFU-F) formed in ERRγ +/- versus ERRγ +/+ stromal cell cultures, suggesting that ERRγ negatively regulates osteoblast differentiation and matrix mineralization but not mesenchymal precursor number. By co-immunoprecipitation experiments, we found that ERRγ and RUNX2 interact in an ERRγ DNA binding domain (DBD)-dependent manner. Treatment of post-confluent differentiating bone marrow stromal cell cultures with Runx2 antisense oligonucleotides resulted in a reduction of CFU-ALP/CFU-O in ERRγ +/- but not ERRγ +/+ mice compared to their corresponding sense controls. Our data indicate that ERRγ is not required for skeletal development but is a sex-dependent negative regulator of postnatal bone formation, acting in a RUNX2- and apparently differentiation stage-dependent manner.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0109592

  10 / 312476 MEDLINE  
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[PMID]: 25317169
[Au] Autor:Dong Y; Yang L; Yang L; Zhao H; Zhang C; Wu D
[Ad] Address:Department of Orthopedics, the First Affiliated Hospital of Xinxiang Medical College, Weihui, Henan Province, China....
[Ti] Title:Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury.
[So] Source:Neural Regen Res;9(16):1520-4, 2014 Aug 15.
[Is] ISSN:1673-5374
[Cp] Country of publication:India
[La] Language:eng
[Ab] Abstract:Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1410
[Cu] Class update date: 141018
[Lr] Last revision date:141018
[Da] Date of entry for processing:141015
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.4103/1673-5374.139478


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