tbuckley/cabot-search huggingface dataset:
CREPT Accelerates Tumorigenesis by Regulating the Transcription of Cell-Cycle-Related Genes
Authors: Dongdong Lu, Yinyuan Wu, Yinyin Wang, Fangli Ren, Dianjun Wang, Fuqin Su, Yanquan Zhang, Xi Yang, Guihua Jin, Xinbao Hao, Dacheng He, Yonggong Zhai, David M. Irwin, Jim Hu, Joseph J.Y. Sung, Jun Yu, Baoqing Jia, Zhijie Chang
Journal: Cancer Cell (2012)
Lack of collagen VIII reduces fibrosis and promotes early mortality and cardiac dilatation in pressure overload in mice†
Authors: Biljana Skrbic, Kristin V.T. Engebretsen, Mari E. Strand, Ida G. Lunde, Kate M. Herum, Henriette S. Marstein, Ivar Sjaastad, Per K. Lunde, Cathrine R. Carlson, Geir Christensen, Johannes L. Bjørnstad, Theis Tønnessen
Journal: Cardiovascular Research (2015)

In pressure overload, left ventricular (LV) dilatation is a key step in transition to heart failure (HF). We recently found that collagen VIII (colVIII), a non-fibrillar collagen and extracellular matrix constituent, was reduced in hearts of mice with HF and correlated to degree of dilatation. A reduction in colVIII might be involved in LV dilatation, and we here examined the role of reduced colVIII in pressure overload-induced remodelling using colVIII knock-out (col8KO) mice. Col8KO mice exhibited increased mortality 3–9 days after aortic banding (AB) and increased LV dilatation from day one after AB, compared with wild type (WT). LV dilatation remained increased over 56 days. Forty-eight hours after AB, LV expression of main structural collagens (I and III) was three-fold increased in WT mice, but these collagens were unaltered in the LV of col8KO mice together with reduced expression of the pro-fibrotic cytokine TGF-β, SMAD2 signalling, and the myofibroblast markers Pxn, α-SMA, and SM22. Six weeks after AB, LV collagen mRNA expression and protein were increased in col8KO mice, although less pronounced than in WT. In vitro, neonatal cardiac fibroblasts from col8KO mice showed lower expression of TGF-β, Pxn, α-SMA, and SM22 and reduced migratory ability possibly due to increased RhoA activity and reduced MMP2 expression. Stimulation with recombinant colVIIIα1 increased TGF-β expression and fibroblast migration. Lack of colVIII reduces myofibroblast differentiation and fibrosis and promotes early mortality and LV dilatation in response to pressure overload in mice.
Characterization of miRNAs circulating in sepsis patients' serum
Authors: Lixin Xie, Huijuan Wang, Weijun Chen, Pengjun Zhang, Longxiang Su
Journal: European Respiratory Journal (2011)

Background:  MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate mRNA expression at the post-transcriptional level and thereby regulate fundamental biological processes. A number of methods, such as multiplex polymerase chain reaction microarrays, have been developed to profile the levels of known miRNAs. However, these methods cannot identify novel miRNAs or accurately determine their expressions over a range of concentrations. Deep sequencing methods provide a suitable platform for genome wide transcriptome analysis and can identify novel transcripts.   Methodology/Principal findings:  We isolated total RNA from serum samples of 9 sepsis patients. We sequenced circulating miRNAs in small RNA libraries using Solexa sequencing. This revealed a total of 154 known mature and 25 mature-star sequences, and predicted 38 novel miRNAs candidates. The miRNA expression profiles of sepsis patients were different from those of healthy controls previously reported by Chen et al. The uniquely biased distributions of nucleotides may be related to the stability of circulating miRNAs.   Conclusion:  Some of these novel candidate miRNAs may be specific to sepsis patients and could be used as biomarkers to evaluate sepsis prognosis by measuring their levels in blood. Follow-up studies on the functional roles of these novel miRNAs and identifying their targets should provide additional insights on the development and progression of sepsis.
The Measles Epidemic
Authors: Donald A. Henderson
Journal: JAMA (1991)

The nation has experienced a marked increase in measles cases during 1989 and 1990. Almost one half of all cases have occurred in unvaccinated preschool children, mostly minorities. The principal cause for the epidemic is failure to provide vaccine to vulnerable children on schedule. Major reasons for the low vaccine coverage exist within the health care system itself, which creates barriers to obtaining immunization and fails to take advantage of many opportunities to provide vaccines to children. Ideally, immunizations should be given as part of a comprehensive child health care program. However, immunization cannot await the development of such an ideal system. Essential changes can and should be made now. Specific recommendations include improved availability of immunization; improved management of immunization services; improved capacity to measure childhood immunization status; implementation of the two-dose measles vaccine strategy; and laboratory, epidemiologic, and operational studies to further define the determinants of decreased vaccine coverage and to develop new combinations of vaccines that can be administered earlier in life. The measles epidemic may be a warning flag of problems with our system of primary health care. (<i>JAMA</i>. 1991;266:1547-1552)
Measuring exhaled nitric oxide: not only a matter of how--but also why--should we do it?
Authors: AT Dinh-Xuan, J Texereau
Journal: European Respiratory Journal (1998)

The biological functions of nitric oxide are so diverseand complex that it is now becoming increasingly difficultto delineate briefly the physiological roles and pathophys-iological implications of this seemingly simple messengermolecule [1]. In respiratory medicine, NO can either beviewed as a paracrine factor (derived from endothelium,epithelium, nerves, inflammatory cells,
Hypoxia-Inducible Factor-1α Is a Key Regulator of Metastasis in a Transgenic Model of Cancer Initiation and Progression
Authors: Debbie Liao, Courtney Corle, Tiffany N. Seagroves, Randall S. Johnson
Journal: Cancer Research (2007)

Abstract Adaptation to hypoxia is a critical step in tumor progression and is, in part, regulated by the transcription factor hypoxia-inducible factor-1α (HIF-1α). Xenograft models have been extensively used to characterize the role of HIF-1α in experimental cancers. Although these models provide an understanding of tumor growth at terminal stages of malignancy, they do not address tumor initiation or metastatic progression. To elucidate these roles, HIF-1α was conditionally deleted in the mammary epithelium of a transgenic mouse model for metastatic breast cancer. Conditional deletion of HIF-1α in the mammary epithelium resulted in delayed tumor onset and retarded tumor growth; this was correlated with decreased tumor cell proliferation. Tumors with conditional deletion of HIF-1α were also less vascular during early tumor progression. Perhaps most surprisingly, deletion of HIF-1α in the mammary epithelium resulted in decreased pulmonary metastasis. These results show that whereas HIF-1α is not required for the initiation of breast tumor growth or tumor cell metastasis, the transcriptional activity of HIF-1α is a significant positive regulator of tumor progression and metastatic potential. [Cancer Res 2007;67(2):563–72]
Simultaneous bilateral elbow dislocation in an international gymnast
Authors: A. A. Syed, J. O'Flanagan
Journal: British Journal of Sports Medicine (1999)

Elbow dislocation is a rare injury in elite athletes. We report an unusual case of simultaneous bilateral elbow dislocations with a unilateral radial head fracture in an international female athlete competing on the asymmetrical bars. These injuries require prompt reduction and immediate mobilisation if an abrupt end to a promising career is to be prevented.
Abstract A88: Identification of factors modulating sensitivity to T cell infiltration in the breast cancer setting via next-generation sequencing.
Authors: Sally Amos, Ron de Leeuw, Nikita Kuklev, Juzer Kakal, Sindy Babinsky, Katy Milne, Sara Kost, Doug Freeman, Rob Holt, Peter Watson, Brad Nelson
Journal: Cancer Research (2013)

Abstract Clinical and pre-clinical trials have established that killer (CD8+) T cells can recognize and destroy tumors. The challenge of our time is to address barriers to T cell infiltration into solid tumors and thereby make cancer immunotherapy a powerful, broadly applicable treatment modality. Bilateral breast cancer represents a unique opportunity to identify those proteins that modulate immune cell entry into solid tumors. Bilateral synchronous breast cancer is when tumors arise independently in separate breasts of the same patient at the same time. Similar to the powerful use of “twin studies” in epidemiology, bilateral tumors provide an opportunity to explore two independent tumorigenic events against a common genetic (and immunological) background. We hypothesise that the sensitivity of breast cancers to T cell infiltration can be predicted on the basis of their molecular profiles. To assess this question, a cohort of bilateral and unilateral breast cancer tissues has been assembled in collaboration with CTRNet-affiliated biobanks. Our objective was to identify 10 tumor pairs with differential T cell infiltration. Here we present the novel protocol for multi-colour brightfield immunohistochemistry (IHC) which was used to quantitate multiple lymphocyte subsets in these precious specimens at the same time. A workflow for automated image collection is presented, which is geared to the analysis of whole-tumour sections. Our results demonstrate that bilateral breast tumors often show differential lymphocyte infiltration despite being exposed to the same level of systemic immunity. Paired tumors will be subjected to whole transcriptome sequencing and lymphocyte receptor spectratyping to identify proteins that distinguish infiltrated from non-infiltrated tumors. Thus, patients with bilateral breast cancer have provided a powerful, translationally-relevant opportunity to study local barriers to T cell infiltration in solid tumors. Citation Format: Sally Amos, Ron de Leeuw, Nikita Kuklev, Juzer Kakal, Sindy Babinsky, Katy Milne, Sara Kost, Doug Freeman, Rob Holt, Peter Watson, Brad Nelson. Identification of factors modulating sensitivity to T cell infiltration in the breast cancer setting via next-generation sequencing. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A88.
Crackles' sensitivity to pulmonary rehabilitation
Authors: Cristina Jácome, Alda Marques
Journal: European Respiratory Journal (2014)

FEV1, despite being the global outcome for chronic obstructive pulmonary disease (COPD), is poorly responsive to pulmonary rehabilitation (PR). Adventitious respiratory sounds, namely crackles, are a promising measure to assess the effectiveness of respiratory interventions on lung function. However, crackles' sensitivity to PR has never been explored. Thus, this study explored the sensitivity of crackles' characteristics to PR.

Sixteen patients with COPD (67±10yrs; 11 male) enrolled in a 12-week PR program. FEV1 and respiratory sounds were assessed pre/post PR. Respiratory sounds were recorded simultaneously at posterior right/left chest using stethoscopes with microphones in the main tube. Airflow was standardised (1l/s) and recorded with a pneumotachograph. Breathing phases were automatically detected using the recorded airflow and crackles using an algorithm based on Hadjileontiadis & Rekanos (2003) and Sevcik (2010).

After PR, FEV1 (70±23 vs 71±25pp; p=.472) and crackles' initial deflection width (IDW: 2±0.3 vs 2.3±0.4ms; p=.118), did not change. However, a decrease in the number of inspiratory (1.5±1 vs 1.1±0.7; p=.076) and expiratory (1.3±1 vs 0.5±0.3; p=.017) crackles was observed. Crackles' largest deflection width (LDW: 2.6±0.4 vs 3±0.4ms; p=.002), two cycle duration (2CD: 9.8±1.5 vs 11.2±1.5ms; p=.008) and frequency (183±33 vs 157±23Hz; p=.008) also changed significantly with the intervention.

Crackles' number, LDW, 2CD and frequency seem to be sensitive measures to lung function changes after PR. IDW was not sensitive to change. This may be due to difficulties in determine the beginning of a crackle. Future studies should explore crackles' sensitivity to PR with larger samples and distinct respiratory diseases.
Genome sequence of the stramenopile Blastocystis, a human anaerobic parasite
Authors: France Denoeud, Michaël Roussel, Benjamin Noel, Ivan Wawrzyniak, Corinne Da Silva, Marie Diogon, Eric Viscogliosi, Céline Brochier-Armanet, Arnaud Couloux, Julie Poulain, Béatrice Segurens, Véronique Anthouard, Catherine Texier, Nicolas Blot, Philippe Poirier, Geok Choo Ng, Kevin SW Tan, François Artiguenave, Olivier Jaillon, Jean-Marc Aury, Frédéric Delbac, Patrick Wincker, Christian P Vivarès, Hicham El Alaoui
Journal: Genome biology (2011)

Abstract Background Blastocystis is a highly prevalent anaerobic eukaryotic parasite of humans and animals that is associated with various gastrointestinal and extraintestinal disorders. Epidemiological studies have identified different subtypes but no one subtype has been definitively correlated with disease. Results Here we report the 18.8 Mb genome sequence of a Blastocystis subtype 7 isolate, which is the smallest stramenopile genome sequenced to date. The genome is highly compact and contains intriguing rearrangements. Comparisons with other available stramenopile genomes (plant pathogenic oomycete and diatom genomes) revealed effector proteins potentially involved in the adaptation to the intestinal environment, which were likely acquired via horizontal gene transfer. Moreover, Blastocystis living in anaerobic conditions harbors mitochondria-like organelles. An incomplete oxidative phosphorylation chain, a partial Krebs cycle, amino acid and fatty acid metabolisms and an iron-sulfur cluster assembly are all predicted to occur in these organelles. Predicted secretory proteins possess putative activities that may alter host physiology, such as proteases, protease-inhibitors, immunophilins and glycosyltransferases. This parasite also possesses the enzymatic machinery to tolerate oxidative bursts resulting from its own metabolism or induced by the host immune system. Conclusions This study provides insights into the genome architecture of this unusual stramenopile. It also proposes candidate genes with which to study the physiopathology of this parasite and thus may lead to further investigations into Blastocystis -host interactions.
Lethal Hepatic Necrosis After Therapy With Imipramine and Desipramine
Authors: W. John Powell
Journal: JAMA (1968)

An apparently allergic reaction manifested by exfoliative dermatitis, mucous membrane desquamation, eosinophilia, severe hepatitis, and death occurred in an 80-year-old woman after therapy with imipramine hydrochloride and desipramine hydrochloride. Autopsy showed massive central and midzonal hepatic necrosis. To the authors' knowledge this is the first report of a lethal hepatic hypersensitivity reaction following administration of these drugs.
Exocrine and endocrine pancreatic function in diabetes mellitus and chronic pancreatitis
Authors: N. Peters, A. P. Dick, C. N. Hales, D. H. Orrell, M. Sarner
Journal: Gut (1966)

EDITORIAL SYNOPSIS Endocrine and exocrine pancreatic function was studied in a small group of controlled patients and in patients with chronic pancreatitis and with mild diabetes mellitus.Patients with chronic pancreatitis showed impaired production of pancreatic enzyme and inadequate production of insulin but no close correlation between exocrine and endocrine function could be demonstrated.Patients with diabetes mellitus show normal exocrine function but plasma insulin concentration was equal to or greater than normal.METHODS EXOCRINE FUNCTION The patient was intubated with an Abbott-Rawson double-lumen tube, having been starved 277 on August 21,
Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite
Authors: Ming-Hui Zou, Chaomei Shi, Richard A. Cohen
Journal: Journal of Clinical Investigation (2002)

Nitric oxide (NO) is produced by NO synthase (NOS) in many cells and plays important roles in the neuronal, muscular, cardiovascular, and immune systems. In various disease conditions, all three types of NOS (neuronal, inducible, and endothelial) are reported to generate oxidants through unknown mechanisms. We present here the first evidence that peroxynitrite (ONOO(-)) releases zinc from the zinc-thiolate cluster of endothelial NOS (eNOS) and presumably forms disulfide bonds between the monomers. As a result, disruption of the otherwise SDS-resistant eNOS dimers occurs under reducing conditions. eNOS catalytic activity is exquisitely sensitive to ONOO(-), which decreases NO synthesis and increases superoxide anion (O(2)(.-)) production by the enzyme. The reducing cofactor tetrahydrobiopterin is not oxidized, nor does it prevent oxidation of eNOS by the same low concentrations of OONO(-). Furthermore, eNOS derived from endothelial cells exposed to elevated glucose produces more O(2)(.-), and, like eNOS purified from diabetic LDL receptor-deficient mice, contains less zinc and fewer SDS-resistant dimers. Hence, eNOS exposure to oxidants including ONOO(-) causes increased enzymatic uncoupling and generation of O(2)(.-) in diabetes, contributing further to endothelial cell oxidant stress. Regulation of the zinc-thiolate center of NOS by ONOO(-) provides a novel mechanism for modulation of the enzyme function in disease.
The Blood-Brain Barrier in Neuroinflammatory Diseases
Authors: Helga E. de Vries, Johan Kuiper, Albertus G. de Boer, Theo J. C. Van Berkel, Douwe D. Breimer
Journal: Pharmacological Reviews (1997)

The existence of the blood-brain barrier (BBB)bwas revealed through studies by [Ehrlich (1885)][1] in the late 19th century, describing that brain tissue remained unstained after injection of a vital dye into the systemic blood circulation of rats. In contrast, the brain tissue was stained after
Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: a single-group phase 2 trial
Authors: Tim Eisen, Heikki Joensuu, Paul D Nathan, Peter G Harper, Marek Z Wojtukiewicz, Steve Nicholson, Amit Bahl, Piotr Tomczak, Seppo Pyrhonen, Kate Fife, Petri Bono, Jane Boxall, Andrea Wagner, Michael Jeffers, Tiffany Lin, David I Quinn
Journal: The Lancet Oncology (2012)
Endothelium-Specific In Vivo Gene Transfer
Authors: Andrew H. Schulick, Gang Dong, Kurt D. Newman, Renu Virmani, David A. Dichek
Journal: Circulation Research (1995)

Abstract Targeted expression of genetic material within the vascular endothelium is potentially a powerful tool for the investigation of endothelial cell (EC) biology. We developed, optimized, and characterized an efficient somatic transgenic model of EC-specific gene transfer. Rat carotid arteries were infused with adenovirus expressing a β-galactosidase (β-gal) gene. The level and cell-type specificity of recombinant gene expression were measured by assaying β-gal activity in vessel extracts and by counting transduced cells in histological sections. Toxicity was evaluated by counting total ECs (3 days) and by measuring neointimal formation (14 days). Effects of transduction on the proliferation of vascular cells were measured with bromodeoxyuridine and [ 3 H]thymidine. Maximum recombinant gene expression resulted from infusion of 1×10 10 to 1×10 11 plaque-forming units (pfu) per milliliter; ≈35% of luminal ECs were transduced. A high degree of EC specificity (90% to 98% of total transduced cells) was maintained over this range of virus concentrations. More highly concentrated virus resulted in loss of β-gal expression and a large decrease in luminal EC number (97% decrease, P &lt;.001). Gene transfer at 4×10 10 pfu/mL was efficient, preserved EC integrity, and caused minimal neointimal formation. After gene transfer, there were early (3-day) increases in both EC and smooth muscle cell proliferation. At 14 days, only EC proliferation remained elevated (18% versus 1.4% in vehicle-infused arteries, P =.005). This animal model permits efficient highly EC-specific gene transfer. Vascular toxicity is minimal, although the EC proliferative index is elevated. This model will be useful in experiments that elucidate the biological role of EC gene products and define pathways of EC gene regulation and signal transduction in vivo.
Long-Term Benefits of 5 Years of Tamoxifen: 10-Year Follow-Up of a Large Randomized Trial in Women at Least 50 Years of Age With Early Breast Cancer
Authors: Allan Hackshaw, Michael Roughton, Sharon Forsyth, Kathryn Monson, Krystyna Reczko, Richard Sainsbury, Michael Baum
Journal: Journal of Clinical Oncology (2011)

The Cancer Research UK "Over 50s" trial compared 5 and 2 years of tamoxifen in women with early breast cancer. Results are reported after median follow-up of 10 years.Between 1987 and 1997, 3,449 patients age 50 to 81 years with operable breast cancer who had been taking 20 mg of tamoxifen for 2 years were randomly assigned to either stop or continue for an additional 3 years, if they were alive and recurrence free. Data on recurrences, new tumors, deaths, and cardiovascular events were obtained (April 2010).There were 1,103 recurrences, 755 deaths as a result of breast cancer, 621 cardiovascular (CV) events, and 236 deaths as a result of CV events. Fifteen years after starting treatment, for every 100 women who received tamoxifen for 5 years, 5.8 fewer experienced recurrence, compared with those who received tamoxifen for 2 years. The risk of contralateral breast cancer was significantly reduced (hazard ratio, 0.70; 95% CI, 0.48 to 1.00). Among women age 50 to 59 years, there was a 35% reduction in CV events (P = .005) and 59% reduction in death as a result of a CV event (P = .02); in older women, the effect was much smaller and not statistically significant.Taking tamoxifen for the recommended 5 years reduces the risk of recurrence or contralateral breast cancer 15 years after starting treatment. It also lowers the risk of CV disease and death as a result of a CV event, particularly among those age 50 to 59 years. Women should therefore be encouraged to complete the full course. Although aromatase inhibitors improve disease-free survival, tamoxifen remains a cheap and highly effective alternative, particularly in developing countries.