tbuckley/cabot-search huggingface dataset:
Acute Lymphocytic Leukemia-Associated Cell Membrane Antigen<xref ref-type="fn" rid="FN2">2</xref>
Authors: Ronald Billing, Jun Minowada, M. Cline, Bill Clark, Kathy Lee
Journal: JNCI Journal of the National Cancer Institute (1978)

Antisera were raised in New Zealand White rabbits against non-B, non-T acute lymphocytic leukemia (ALL) cells coated with antilymphocyte serum. Following minimal absorption with chronic lymphocytic leukemia (CLL) cells, the antiserum reacted mainly with non-B, non-T ALL cells. The following numbers of patients had leukemia cells that reacted with the ALL antisera: 13 of 18 with ALL, 3 of 27 with acute myelocytic leukemia, 1 of 8 with chronic myelocytic leukemia (CML), and 0 of 12 with CLL. The positive CML was a patient in CML blast crisis. Normal peripheral blood B- and T-lymphocytes and normal bone marrow were negative. Reactions of the anti-ALL serum (136K) were compared with the reactions of a rabbit anti-B-cell antiserum (63K) that reacted with approximately 70% of leukemia cells. Cultured lymphoblastoid cell lines from normal donors were negative by both cytotoxicity and immunofluorescence tests. However, by immunofluorescence testing, 8 of 17 known malignant lines from a variety of lymphoproliferative disorders were positive; 4 of these lines were of T-cell origin. By immunoprecipitation and polyacrylamide gel electrophoresis, the ALL antigen appeared to consist of a single polypeptide chain of approximately 98,000 daltons. The anti-ALL antiserum was not cytotoxic for normal myeloid stem cells (colony-forming units).
Prevention of ankle sprains in sport: a systematic literature review
Authors: Y Kaplan
Journal: British Journal of Sports Medicine (2011)

Background Ankle sprains are the most common musculoskeletal injuries that occur in athletes. The importance of finding ways to prevent these injuries is therefore of paramount importance to athletes, their teams and the medical system as a whole. Objective To review the published evidence on the effectiveness of various methods in the prevention of ankle sprains in the athletic population. Design A literature search was conducted using multiple databases and only included prospective, level 1 and 2, randomised and quasi-randomised controlled trials (RCTs) published between 1980 and August 2010. Keywords used in the search were prevention in combination with ankle sprains. Results Overall, 19 RCTs were reviewed consisting of a total of 12 233 participants. The studies showed a significant reduction in the number of ankle sprains in individuals allocated to an external ankle support group. This reduction was greater for those with a previous history of ankle sprains. Braces seemed to be more effective in preventing ankle sprains than tape. Appropriately applied braces, tape or orthoses, do not adversely affect performance. Proprioceptive training reduced the incidence of ankle sprains in athletes with recurrent ankle sprains to the same level as subjects without any history of ankle sprains. Conclusion Semi–rigid orthoses or aircasts are more effective than taping to reduce the incidence of sprains. Sensori-motor control can seemingly be improved in previously injured ankles, such that the risk equals that of healthy ankles. Rules must be changed to limit contact between players and possibly harsher penalties introduced. When the above interventions are utilised effectively, ankle sprains can be significantly prevented.
Human tumor necrosis factor alpha gene regulation in phorbol ester stimulated T and B cell lines.
Authors: A E Goldfeld, J L Strominger, C Doyle
Journal: The Journal of Experimental Medicine (1991)

The minimal region of the human tumor necrosis factor alpha (TNF-alpha) gene promoter necessary for its transcriptional induction by phorbol esters (PMA) in human T and B lymphocyte cell lines has been localized between -52 and +89 nucleotides (nt) relative to the gene's transcriptional start site. Comparison of these sequences to those required to mediate virus or lipopolysaccharide (LPS) induction of the gene reveal significant differences, and thus, the sequence requirements for PMA induction are distinct from those that mediate induction by virus or LPS. Although three sites in the TNF-alpha promoter (kappa 1, kappa 2, and kappa 3) specifically bind the transcription factor NF-kappa B in lymphoid nuclear extracts, TNF-alpha mRNA induction by PMA does not correlate with NF-kappa B binding activities displayed by different T and B cell lines. Moreover, kappa 1-kappa 3 can each be deleted from the TNF-alpha promoter with little effect on the gene's inducibility by PMA. Therefore, TNF-alpha mRNA induction by PMA, like its induction by virus and LPS, is not primarily mediated by NF-kappa B, but rather is mediated through other sequences and protein factors. Surprisingly, multimers of kappa 1-kappa 3 can confer PMA inducibility on a heterologous promoter in a B (Raji), but not a T (HUT78) cell line. However they are not functional on a truncated TNF-alpha promoter, indicating that promoter context and cell type specificity influence the PMA inducible function of these NF-kappa B binding sites.
Anatomy and biochemistry of entheses
Authors: MICHAEL BENJAMIN, MATTHIAS BOLLOW, JÃœRGEN BRAUN, JAN BRANDT, JÃœRGEN BRAUN, JÃœRGEN BRAUN, JOACHIM SIEPER, RUBÃ‰N BURGOS-VARGAS, PASCAL CLAUDEPIERRE, KURT DE VLAM, ERIC VEYS, FRITS EULDERINK, MICHAEL BENJAMIN, MATTHIAS BOLLOW, JÃœRGEN BRAUN, JAN BRANDT, JÃœRGEN BRAUN, JÃœRGEN BRAUN, JOACHIM SIEPER, RUBÃ‰N BURGOS-VARGAS, PASCAL CLAUDEPIERRE, JÃ–RG KRIEGSMANN, STEFFEN GAY, MARJATTA LEIRISALO-REPO, MATTHIAS BOLLOW, JÃœRGEN BRAUN, JAN BRANDT, JÃœRGEN BRAUN, JÃœRGEN BRAUN, JOACHIM SIEPER, RUBÃ‰N BURGOS-VARGAS, PASCAL CLAUDEPIERRE, YIPING ZHANG, A ROBIN POOLE
Journal: Annals of the Rheumatic Diseases (2000)

There are two different types of entheses. Fibrous entheses are characterised by pure dense fibrous connective tissue that links the tendon or ligament to the bone, but fibrocartilaginous entheses have a transitional zone of fibrocartilage at the bony interface. Most entheses are fibrocartilaginous—for example, those of the annulus fibrosus, Achilles tendon, and most insertions on long bone epiphyses or apophyses. Typically, four zones of tissue are present—dense fibrous connective tissue, uncalcified fibrocartilage, calcified fibrocartilage, and bone. The two fibrocartilage zones are separated by a calcification front known as the tidemark.

 Uncalcified fibrocartilage probably reduces stress concentration by gradually dissipating any fibre bending and stretch-induced narrowing of the tendon/ligament away from the junctional region where wear and tear are most likely to occur. It is prominent at sites at which a great deal of bending of the tendon/ligament accompanies joint movement. It also creates a vascular and cellular barrier between bone and tendon/ligament cells.

 The calcified fibrocartilage serves to link the tendon/ligament to the bone via an irregular interface—probably in the manner of a jigsaw, with little direct continuity of collagen fibres. The stress dissipation role of enthesis fibrocartilage hinges on its compression tolerance properties—any bending or narrowing of a tendon/ligament increases compressive loading. As in articular cartilage, its ability to resist compression is linked to the presence of aggrecan and type II collagen in the extracellular matrix. These molecules have been demonstrated at several entheses by rerverse transcriptase-polymerase chain reaction, western blotting, and/or immunohistochemistry. At most sites, they are synthesised by fibrocartilage cells that appear relatively late in development by fibroblast metaplasia. In the inner annulus, however, the fibrocartilage is derived from hyaline cartilage that is present during early development.

# Enthesophytes develop by endochondral ossification in enthesis fibrocartilage and their formation can be an extension of normal enthesis development: detailed MRI assessments of the axial skeleton in spondyloarthropathy {#article-title-2}

The sacroiliac joints (SIJ) are initially affected in most patients with ankylosing spondylitis (AS). In later stages affection of vertebral …
GPR54 and kisspeptin in reproduction
Authors: Manuel Tena-Sempere
Journal: Human Reproduction Update (2006)

Kisspeptins, the peptide products of the KiSS-1 gene, were identified in 2001 as natural ligands of the previously orphan G protein-coupled receptor, GPR54. They include, among others, metastin and kisspeptin-10. The known biological functions of kisspeptins were initially restricted to their ability to suppress tumour metastasis, hence the name of metastin. However, in late 2003, two groups independently reported that loss-of-function mutations of the GPR54 gene are linked to absence of puberty onset and hypogonadotrophic hypogonadism in humans—a phenotype that was reproduced in GPR54-null mice. Those seminal observations revealed a totally unexpected, fundamental role of the KiSS-1/GPR54 system in control of puberty and reproductive function and boosted an extraordinary interest for the characterization of these novel facets of kisspeptin physiology. Indeed, in the last 2 years, metastin and kisspeptin-10 have been demonstrated as very potent stimulators of the gonadotrophic axis, in a number of species and through different routes of administration. In addition, the hypothalamic KiSS-1/GPR54 system has been proven as an essential gatekeeper of GnRH neurons, involved in their activation at puberty and their regulation by gonadal steroids and (probably) metabolic factors. This review comprehensively examines the experimental evidence obtained to date supporting a pivotal role of kisspeptins and GPR54 in the control of reproduction.
Overcoming Persistent Dependency on Androgen Signaling after Progression to Castration-Resistant Prostate Cancer
Authors: Masuo Yamaoka, Takahito Hara, Masami Kusaka
Journal: Clinical Cancer Research (2010)

Prostate cancer is the most common form of cancer in males in the United States, and the second leading cause of cancer death. Initially, most cases of prostate cancer respond well to hormone therapy; however, resistance often develops rapidly, leading to castration-resistant prostate cancer (CRPC). Several mechanisms for castration resistance have been proposed, of which the most significant seems to be the "intracrine" production of androgens from adrenal androgen or intratumorally via the de novo route. This mechanism stimulates disease progression through reactivation of androgen receptor signaling in patients who have previously undergone castration therapy. 17,20-lyase is essential for androgen synthesis in both the adrenal glands and CRPC tissue, and some 17,20-lyase inhibitors and second-generation anti-androgens that were developed to treat CRPC are currently under clinical investigation, with encouraging preliminary data reported so far. However, resistance to some of these therapies has already been noted. The study of circulating tumor cells will likely be important not only to identify patients likely to receive benefit from this therapeutic approach, but also to further understand the molecular mechanisms of resistance.
Targets of Balancing Selection in the Human Genome
Authors: A. M. Andres, M. J. Hubisz, A. Indap, D. G. Torgerson, J. D. Degenhardt, A. R. Boyko, R. N. Gutenkunst, T. J. White, E. D. Green, C. D. Bustamante, A. G. Clark, R. Nielsen
Journal: Molecular Biology and Evolution (2009)

Balancing selection is potentially an important biological force for maintaining advantageous genetic diversity in populations, including variation that is responsible for long-term adaptation to the environment. By serving as a means to maintain genetic variation, it may be particularly relevant to maintaining phenotypic variation in natural populations. Nevertheless, its prevalence and specific targets in the human genome remain largely unknown. We have analyzed the patterns of diversity and divergence of 13,400 genes in two human populations using an unbiased single-nucleotide polymorphism data set, a genome-wide approach, and a method that incorporates demography in neutrality tests. We identified an unbiased catalog of genes with signatures of long-term balancing selection, which includes immunity genes as well as genes encoding keratins and membrane channels; the catalog also shows enrichment in functional categories involved in cellular structure. Patterns are mostly concordant in the two populations, with a small fraction of genes showing population-specific signatures of selection. Power considerations indicate that our findings represent a subset of all targets in the genome, suggesting that although balancing selection may not have an obvious impact on a large proportion of human genes, it is a key force affecting the evolution of a number of genes in humans.
Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control
Authors: Michelle Hong, Anne-Laure Puaux, Caleb Huang, Laure Loumagne, Charlene Tow, Charles Mackay, Masashi Kato, Armelle Prévost-Blondel, Marie-Françoise Avril, Alessandra Nardin, Jean-Pierre Abastado
Journal: Cancer Research (2011)

T-cell infiltration is known to impact tumor growth and is associated with cancer patient survival. However, the molecular cues that favor T-cell infiltration remain largely undefined. Here, using a genetically engineered mouse model of melanoma, we show that CXCR3 ligands and CCL5 synergize to attract effector T cells into cutaneous metastases, and their expression inhibits tumor growth. Treatment of tumor-bearing mice with chemotherapy induced intratumoral expression of these chemokines and favored T-cell infiltration into cutaneous tumors. In patients with melanoma, these chemokines were also upregulated in chemotherapy-sensitive lesions following chemotherapy, and correlated with T-cell infiltration, tumor control, and patient survival. We found that dacarbazine, temozolomide, and cisplatin induced expression of T-cell-attracting chemokines in several human melanoma cell lines in vitro. These data identify the induction of intratumoral expression of chemokines as a novel cell-extrinsic mechanism of action of chemotherapy that results in the recruitment of immune cells with antitumor activity. Therefore, identifying chemotherapeutic drugs able to induce the expression of T-cell-attracting chemokines in cancer cells may represent a novel strategy to improve the efficacy of cancer immunotherapy.
Regulation of accumulation and function of myeloid derived suppressor cells in different murine models of hepatocellular carcinoma
Authors: Tamar Kapanadze, Jaba Gamrekelashvili, Chi Ma, Carmen Chan, Fei Zhao, Stephen Hewitt, Lars Zender, Veena Kapoor, Dean W. Felsher, Michael P. Manns, Firouzeh Korangy, Tim F. Greten
Journal: Journal of Hepatology (2013)
Response to Letter Regarding Article, “Endocarditis Secondary to <i>Microsporidia</i> : Giant Vegetation in a Pacemaker User”
Authors: Martino Martinelli Filho, Henrique B. Ribeiro, Leonardo J.C. Paula, Silvana A.D. Nishioka, Wagner T. Tamaki, Roberto Costa, Sérgio F. Siqueira, Joyce T. Kawakami, Maria Lourdes Higuchi
Journal: Circulation (2010)
Diabetes Is Associated With Dramatically Decreased Survival in Female but Not Male Subjects With Cystic Fibrosis
Authors: Carlos E. Milla, Joanne Billings, Antoinette Moran
Journal: Diabetes Care (2005)

OBJECTIVE—Survival analysis was performed on a prospectively followed cohort of patients with cystic fibrosis (CF) to determine the impact of the development of diabetes on survival. RESEARCH DESIGN AND METHODS—Clinical data were retrieved for patients diagnosed with CF-related diabetes (CFRD) at the Minnesota CF Center in 1987–2002. Kaplan-Meier survival analysis was performed to estimate median survival. Data were analyzed by Cox regression to evaluate the influence of clinical characteristics at the time of CFRD diagnosis on mortality. RESULTS—Clinical information was reviewed from 1,081 CF patients. A total of 123 patients with CFRD with fasting hyperglycemia were identified (58 males). Median survival was 49.5 years for male subjects without diabetes, 47.4 years for male subjects with diabetes, 47.0 years for female subjects without diabetes, and 30.7 years for female subjects with diabetes. Only female sex and forced expiratory volume in 1 s at the time of CFRD diagnosis were significant predictors of the subsequent risk of death (P &amp;lt; 0.001). This strong association was not confounded by CFTR genotype, BMI, steroid use, respiratory pathogens, HbA1c, or pregnancy. CONCLUSIONS—Female subjects with CFRD have a remarkably poorer prognosis compared with all male subjects with CF and female subjects with CF but without diabetes. The etiology of this sex difference is not clear. We speculate it might involve the interaction of female hormones and diabetes on promotion of a proinflammatory state or that androgens might protect male subjects from the catabolic effects of insulin deficiency. Alternatively, the appearance of frank diabetes in female subjects with CF may simply be a marker for some other biological difference that is not immediately apparent.
336 HYPERHOMOCYSTEINEMIA AND C677T METHYLENETETRAHIDROFOLATE REDUCTASE GENE POLYMORPHISMS IN SPANISH PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE
Authors: J.A. Chirinos Vega, M. Perez Carreras, C. Fernández-Miranda, G. López-Alonso, R. Ayala, C. Arribas, G. Castellano
Journal: Journal of Hepatology (2010)
Decitabine Induces Delayed Reactive Oxygen Species (ROS) Accumulation in Leukemia Cells and Induces the Expression of ROS Generating Enzymes
Authors: Tamer E. Fandy, Anchalee Jiemjit, Manjusha Thakar, Paulette Rhoden, Lauren Suarez, Steven D. Gore
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Azanucleoside DNA methyltransferase (DNMT) inhibitors are currently approved by the U.S. Food and Drug Administration for treatment of myelodysplastic syndrome. The relative contributions of DNMT inhibition and other off-target effects to their clinical efficacy remain unclear. Data correlating DNA methylation reversal and clinical response have been conflicting. Consequently, it is necessary to investigate so-called off-target effects and their impact on cell survival and differentiation. Experimental Design: Flow cytometry was used for cell cycle, apoptosis, and reactive oxygen species (ROS) accumulation analysis. Gene expression analysis was performed using real-time PCR. DNA methylation was detected by methylation-specific PCR. Mitochondrial membrane potential was analyzed using JC-1 dye staining. Western blotting was used for quantitative protein expression analysis. Results: 5-Aza-2′-deoxycytidine (DAC) induced cell-cycle arrest and apoptosis in leukemia cells. p53 expression was dispensable for DAC-induced apoptosis. DAC induced delayed ROS accumulation in leukemia cells but not in solid tumor cells and p53 expression was dispensable for ROS increase. ROS increase was deoxycytidine kinase dependent, indicating that incorporation of DAC into nuclear DNA is required for ROS generation. ROS accumulation by DAC was caspase-independent and mediated the dissipation of the mitochondrial membrane potential. Concordantly, ROS scavengers diminished DAC-induced apoptosis. DAC induced the expression of different NADPH oxidase isoforms and upregulated Nox4 protein expression in an ATM-dependent manner, indicating the involvement of DNA damage signaling in Nox4 upregulation. Conclusion: These data highlight the importance of mechanisms other than DNA cytosine demethylation in modulating gene expression and suggest investigating the relevance of ROS accumulation to the clinical activity of DAC. Clin Cancer Res; 20(5); 1249–58. ©2014 AACR.
Annotation of the Drosophila melanogastereuchromatic genome: a systematic review
Authors: Sima Misra, Madeline A Crosby, Christopher J Mungall, Beverley B Matthews, Kathryn S Campbell, Pavel Hradecky, Yanmei Huang, Joshua S Kaminker, Gillian H Millburn, Simon E Prochnik, Christopher D Smith, Jonathan L Tupy, Eleanor J Whitfield, Leyla Bayraktaroglu, Benjamin P Berman, Brian R Bettencourt, Susan E Celniker, Aubrey DNJ de Grey, Rachel A Drysdale, Nomi L Harris, John Richter, Susan Russo, Andrew J Schroeder, ShengQiang Shu, Mark Stapleton, Chihiro Yamada, Michael Ashburner, William M Gelbart, Gerald M Rubin, Suzanna E Lewis
Journal: Genome biology (2002)

The recent completion of the Drosophila melanogaster genomic sequence to high quality and the availability of a greatly expanded set of Drosophila cDNA sequences, aligning to 78% of the predicted euchromatic genes, afforded FlyBase the opportunity to significantly improve genomic annotations. We made the annotation process more rigorous by inspecting each gene visually, utilizing a comprehensive set of curation rules, requiring traceable evidence for each gene model, and comparing each predicted peptide to SWISS-PROT and TrEMBL sequences. Although the number of predicted protein-coding genes in Drosophila remains essentially unchanged, the revised annotation significantly improves gene models, resulting in structural changes to 85% of the transcripts and 45% of the predicted proteins. We annotated transposable elements and non-protein-coding RNAs as new features, and extended the annotation of untranslated (UTR) sequences and alternative transcripts to include more than 70% and 20% of genes, respectively. Finally, cDNA sequence provided evidence for dicistronic transcripts, neighboring genes with overlapping UTRs on the same DNA sequence strand, alternatively spliced genes that encode distinct, non-overlapping peptides, and numerous nested genes. Identification of so many unusual gene models not only suggests that some mechanisms for gene regulation are more prevalent than previously believed, but also underscores the complex challenges of eukaryotic gene prediction. At present, experimental data and human curation remain essential to generate high-quality genome annotations.
Long-Term Persistence of Resistant <i>Enterococcus</i> Species after Antibiotics To Eradicate <i>Helicobacter pylori</i>
Authors: Maria Sjlund, Karin Wreiber, Dan I. Andersson, Martin J. Blaser, Lars Engstrand
Journal: Annals of Internal Medicine (2003)

Background: Antibiotic treatment selects for resistance not only in the pathogen to which it is directed but also in the indigenous microflora. Objective: To determine whether a widely used regimen (clarithromycin, metronidazole, and omeprazole) for Helicobacter pylori eradication affects resistance development in enterococci. Design: Cohort study. Setting: Endoscopy units at 3 community hospitals in Sweden. Patients: 5 consecutive dyspeptic patients who were colonized with H. pylori, had endoscopy-confirmed duodenal ulcer, and received antibiotic treatment, and 5 consecutive controls with dyspepsia but no ulcer who did not receive treatment. Measurements: Fecal samples were obtained from patients and controls before, immediately after, 1 year after, and 3 years after treatment. From each patient and sample, enterococci were isolated and analyzed for DNA fingerprint, clarithromycin susceptibility, and presence of the erm(B) gene. Results: In treated patients, all enterococci isolated immediately after treatment showed high-level clarithromycin resistance due to erm(B). In 3 patients, resistant enterococci persisted for 1 to 3 years after treatment. No resistance developed among controls. Conclusion: A common H. pylori treatment selects for highly resistant enterococci that can persist for at least 3 years without further selection.