tbuckley/cabot-search huggingface dataset:
miR-449 inhibits cell proliferation and is down-regulated in gastric cancer
Authors: Tony Bou Kheir, Ewa Futoma-Kazmierczak, Anders Jacobsen, Anders Krogh, Linda Bardram, Christoffer Hother, Kirsten Grønbæk, Birgitte Federspiel, Anders H Lund, Lennart Friis-Hansen
Journal: Molecular Cancer (2011)

Abstract Background Gastric cancer is the fourth most common cancer in the world and the second most prevalent cause of cancer related death. The development of gastric cancer is mainly associated with H. Pylori infection leading to a focus in pathology studies on bacterial and environmental factors, and to a lesser extent on the mechanistic development of the tumour. MicroRNAs are small non-coding RNA molecules involved in post-transcriptional gene regulation. They are found to regulate genes involved in diverse biological functions and alterations in microRNA expression have been linked to the pathogenesis of many malignancies. The current study is focused on identifying microRNAs involved in gastric carcinogenesis and to explore their mechanistic relevance by characterizing their targets. Results Invitrogen NCode miRNA microarrays identified miR-449 to be decreased in 1-year-old Gastrin KO mice and in H. Pylori infected gastric tissues compared to tissues from wild type animals. Growth rate of gastric cell lines over-expressing miR-449 was inhibited by 60% compared to controls. FACS cell cycle analysis of miR-449 over-expressing cells showed a significant increase in the sub-G 1 fraction indicative of apoptosis. ß-Gal assays indicated a senescent phenotype of gastric cell lines over-expressing miR-449. Affymetrix 133v2 arrays identified GMNN , MET, CCNE2, SIRT1 and CDK6 as miR-449 targets. Luciferase assays were used to confirm GMNN , MET , CCNE2 and SIRT1 as direct targets. We also show that miR-449 over-expression activated p53 and its downstream target p21 as well as the apoptosis markers cleaved CASP3 and PARP. Importantly, qPCR analyses showed a loss of miR-449 expression in human clinical gastric tumours compared to normal tissues. Conclusions In this study, we document a diminished expression of miR-449 in Gastrin KO mice and further confirmed its loss in human gastric tumours. We investigated the function of miR-449 by identifying its direct targets. Furthermore we show that miR-449 induces senescence and apoptosis by activating the p53 pathway.
The Case for Conducting a Randomized Clinical Trial to Assess the Efficacy of a Single Dose of Prophylactic HPV Vaccines Among Adolescents
Authors: Aimée R. Kreimer, Mark E. Sherman, Vikrant V. Sahasrabuddhe, Mahboobeh Safaeian
Journal: JNCI Journal of the National Cancer Institute (2015)

Human papillomavirus (HPV) types 16 and 18 collectively cause approximately 70% of cervical cancers worldwide (1) and are linked to an even higher percentage of HPV-associated anogenital and oropharyngeal cancers (2). Three-dose regimens of prophylactic vaccines (the bivalent vaccine Cervarix, GlaxoSmithKline Biologicals; the quadrivalent vaccine Gardasil, Merck and Co, Inc.) provide nearly complete protection against HPV16 and -18 infections and related cervical lesions among individuals uninfected with these types at the time of vaccination (3,4). The structure of the HPV virus-like particles (VLPs), the key component of HPV prophylactic vaccines, present closely spaced, repetitive epitopes to the immune system that induce highly potent, protective antibody responses (14), which may reduce or eliminate the need for booster doses. Further, the immune-stimulatory effects of a toll-like receptor agonist adjuvant in the bivalent vaccine may also contribute to the magnitude and durability of the immune response to this vaccine.
Expression of human adenosine deaminase in nonhuman primates after retrovirus-mediated gene transfer.
Authors: P W Kantoff, A P Gillio, J R McLachlin, C Bordignon, M A Eglitis, N A Kernan, R C Moen, D B Kohn, S F Yu, E Karson
Journal: The Journal of Experimental Medicine (1987)

Primate bone marrow cells were infected with a retroviral vector carrying the genes for human adenosine deaminase (h-ADA) and bacterial neomycin resistance (neor). The infected cells were infused back into the lethally irradiated donor animals. Several monkeys fully reconstituted and were shown to express the h-ADA and neor genes at low levels in their recirculating hematopoietic cells for short periods of time.
Organisation of the mouse sinoatrial node: structure and expression of HCN channels
Authors: Jie Liu, Halina Dobrzynski, Joseph Yanni, Mark R. Boyett, Ming Lei
Journal: Cardiovascular Research (2006)

Objective: To reveal the structural characteristics of the sinoatrial node (SAN) and the distribution of hyperpolarization-activated cyclic nucleotide-gated cation channels (HCN) in the SAN in the mouse. Methods: The structure of the SAN and the distribution of HCN channels in the SAN in the mouse were studied by histology and immunolabelling of ANP, Cx43 and HCN channels. Results: The mouse SAN is a comma-shaped structure with a length of ∼1.5 mm parallel to the crista terminalis and is separated from atrial muscle by connective tissue at the border both with the crista terminalis and the atrial septum. A unique compact nodal structure with densely-packed nodal cells was identified at the head of the comma-shaped SAN. Cell size and fibre orientation vary regionally in the SAN: the cells in the compact node are small and are orientated perpendicular to the crista terminalis, whereas the cells in the more inferior part are larger and more loosely-packed and are orientated parallel to the crista terminalis. All SAN cells exhibited labelling of HCN4, but no cell exhibited detectable labelling of HCN1, HCN2, ANP and Cx43, while surrounding atrial cells exhibited labelling of ANP and Cx43, but not HCN1, HCN2 and HCN4. A specialised interface between the SAN and surrounding atrial muscle was also identified: strands of HCN4-positive nodal cells protrude into the atrial muscle and strands of Cx43-positive atrial cells protrude into the SAN; thus, there are interdigitations between the SAN and atrial muscle. Conclusions: In the mouse, (i) the SAN is structurally complex with a densely-packed head and loosely-packed tail; (ii) HCN4 is the only HCN isoform detectable and is present throughout the SAN; and (iii) there is a specialised interface between the SAN and surrounding atrium that may be necessary for the SAN to drive the more hyperpolarized atrial muscle.
Optimising end of life care requires an individualised approach
Authors: H. M. Buiting, G. S. Sonke
Journal: BMJ (2014)

Wright and colleagues conclude that patients receiving palliative chemotherapy who have an estimated life expectancy of six months are more likely than those not receiving palliative chemotherapy to experience intensive medical end of life care.1 The authors previously showed that end of life discussions in early stage disease are associated with decreased “aggressive” care.2 We support the identification of early predictors for intensive medical …
Effect of Tourniquet Shock and Acute Hemorrhage on the Circulation of Various Organs in the Rat
Authors: Louis Takács, Kálmán Kállay, Josephine H. Skolnik
Journal: Circulation Research (1962)

Cardiac output, blood pressure, and organ fractions of cardiac output, except the brain, were determined in rats subjected to tourniquet shock and to hemorrhage. Bleeding involved the withdrawal of 23 and 32 ml./Kg. blood, respectively, and determinations were carried out 5 to 20 minutes after bleeding. Sapirstein's "indicator fractionation" method with Rb 86 was used for the determination of the cardiac output fractions. Blood flow and circulatory resistance of the organs were calculated from the experimental data. Cardiac output was not measured after severe (32 ml./Kg.) hemorrhage. In tourniquet shock at 50 mm. Hg blood pressure, the cardiac output and the blood flow in all organs decrease while vascular resistance of the skin and of the "carcass" (skeleton, muscles, endocrine organs) increases. The heart, "lung," and the liver fractions of cardiac output increase, renal and skin fractions decrease. After moderate hemorrhage at 47 mm. Hg blood pressure, cardiac output and the blood flow of the organs are low. Vascular resistance of all organs other than the heart and the "lung" rises. Cardiac output fractions of the heart, "lung," and "carcass" increase; renal and cutaneous fractions decrease. In severe hemorrhage, the redistribution of cardiac output has a similar tendency but is usually more pronounced.
Nowadays, I have no asthma at all!
Authors: Linda Ekerljung, Malin Axelsson
Journal: European Respiratory Journal (2013)

Background:   Personality could influence perceptions of health and health-related behaviour. According to the Five-factor model, personality could be described by five broad and bipolar personality traits. The study aims to explore the influence of personality and asthma control on perceptions of not having asthma in a general population.   Method:   In the context of the population-based West Sweden Asthma Study, 437 adult subjects with current asthma participated in a structured interview and completed questionnaires on personality and asthma control. Subjects with COPD were excluded.   Results:   80 (15%) subjects (51% men) reported that they did not have asthma at all. Characteristic for these 80 subjects were that 40% stated that they mostly were completely without symptoms but from time to time had severe symptoms and 66% stated that they only got asthma in specific situations and by a few triggers. Additionally, they reported better asthma control and scored lower on the personality trait Agreeableness (lower scores include behavioural tendencies like being more competitive, reluctant and sceptical about other people’s intentions) compared to participants who perceived that they had asthma. An increase in Agreeableness was associated with an increase in the odds of perceiving that one had asthma. In contrast, an increase in asthma control was associated with a decrease in the odds of perceiving that one had asthma.   Conclusion:  Despite having asthma symptoms every now and then, perceptions of good asthma control and behavioural tendencies like being reluctant and sceptical could lead to perceptions that one does not have asthma.
Overexpression of GOLPH3 Promotes Proliferation and Tumorigenicity in Breast Cancer via Suppression of the FOXO1 Transcription Factor
Authors: Zhaolei Zeng, Huanxin Lin, Xiaohui Zhao, Guanglin Liu, Xi Wang, Ruihua Xu, Kun Chen, Jun Li, Libing Song
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in various biologic processes. The clinical significance and biologic role of GOLPH3 in breast cancer, however, remains unknown. Experimental Design: Expression of GOLPH3 in normal breast cells, breast cancer cells, and 6-paired breast cancer and adjacent noncancerous tissues were quantified using real-time PCR and Western blotting. GOLPH3 protein expression was analyzed in 258 archived, paraffin-embedded breast cancer samples using immunohistochemistry. The role of GOLPH3 in breast cancer cell proliferation and tumorigenicity was explored in vitro and in vivo. Western blotting and luciferase reporter analyses were used to investigate the effect of GOLPH3 overexpression and silencing on the expression of cell-cycle regulators and FOXO1 transcriptional activity. Results: GOLPH3 was significantly upregulated in breast cancer cells and tissues compared with normal cells and tissues. Immunohistochemical analysis revealed high expression of GOLPH3 in 133 of 258 (51.6%) breast cancer specimens. Statistical analysis showed a significant correlation of GOLPH3 expression with advanced clinical stage and poorer survival. Overexpression and ablation of GOLPH3 promoted and inhibited, respectively, the proliferation and tumorigenicity of breast cancer cells in vitro and in vivo. GOLPH3 overexpression enhanced AKT activity and decreased FOXO1 transcriptional activity, downregulated cyclin-dependent kinase (CDK) inhibitor p21Cip1, p27Kip1, and p57Kip2, and upregulated the CDK regulator cyclin D1. Conclusion: Our results suggest that high GOLPH3 expression is associated with poor overall survival in patients with breast cancer and that GOLPH3 overexpression increases the proliferation and tumorigenicity of human breast cancer cells. Clin Cancer Res; 18(15); 4059–69. ©2012 AACR.
Renalase Prevents AKI Independent of Amine Oxidase Activity
Authors: Ling Wang, Heino Velazquez, Gilbert Moeckel, John Chang, Ahrom Ham, H. Thomas Lee, Robert Safirstein, Gary V. Desir
Journal: Journal of the American Society of Nephrology (2014)

AKI is characterized by increased catecholamine levels and hypertension. Renalase, a secretory flavoprotein that oxidizes catecholamines, attenuates ischemic injury and the associated increase in catecholamine levels in mice. However, whether the amine oxidase activity of renalase is involved in preventing ischemic injury is debated. In this study, recombinant renalase protected human proximal tubular (HK-2) cells against cisplatin- and hydrogen peroxide-induced necrosis. Similarly, genetic depletion of renalase in mice (renalase knockout) exacerbated kidney injury in animals subjected to cisplatin-induced AKI. Interestingly, compared with the intact renalase protein, a 20-amino acid peptide (RP-220), which is conserved in all known renalase isoforms, but lacks detectable oxidase activity, was equally effective at protecting HK-2 cells against toxic injury and preventing ischemic injury in wild-type mice. Furthermore, in vitro treatment with RP-220 or recombinant renalase rapidly activated Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinases and downregulated c-Jun N-terminal kinase. In summary, renalase promotes cell survival and protects against renal injury in mice through the activation of intracellular signaling cascades, independent of its ability to metabolize catecholamines, and we have identified the region of renalase required for these effects. Renalase and related peptides show potential as therapeutic agents for the prevention and treatment of AKI.
Dysregulation of innate immune receptors on neutrophils in chronic granulomatous disease
Authors: Dominik Hartl, Natalie Lehmann, Florian Hoffmann, Annette Jansson, Andreas Hector, Gundula Notheis, Dirk Roos, Bernd H. Belohradsky, Uwe Wintergerst
Journal: Journal of Allergy and Clinical Immunology (2008)
Redox Modification of Ryanodine Receptors Contributes to Sarcoplasmic Reticulum Ca <sup>2+</sup> Leak in Chronic Heart Failure
Authors: Dmitry Terentyev, Inna Györke, Andriy E. Belevych, Radmila Terentyeva, Arun Sridhar, Yoshinori Nishijima, Esperanza Carcache de Blanco, Savita Khanna, Chandan K. Sen, Arturo J. Cardounel, Cynthia A. Carnes, Sandor Györke
Journal: Circulation Research (2008)

Abnormal cardiac ryanodine receptor (RyR2) function is recognized as an important factor in the pathogenesis of heart failure (HF). However, the specific molecular causes underlying RyR2 defects in HF remain poorly understood. In the present study, we used a canine model of chronic HF to test the hypothesis that the HF-related alterations in RyR2 function are caused by posttranslational modification by reactive oxygen species generated in the failing heart. Experimental approaches included imaging of cytosolic ([Ca(2+)](c)) and sarcoplasmic reticulum (SR) luminal Ca(2+) ([Ca(2+)]SR) in isolated intact and permeabilized ventricular myocytes and single RyR2 channel recording using the planar lipid bilayer technique. The ratio of reduced to oxidized glutathione, as well as the level of free thiols on RyR2 decreased markedly in failing versus control hearts consistent with increased oxidative stress in HF. RyR2-mediated SR Ca(2+) leak was significantly enhanced in permeabilized myocytes, resulting in reduced [Ca(2+)](SR) in HF compared to control cells. Both SR Ca(2+) leak and [Ca(2+)](SR) were partially normalized by treating HF myocytes with reducing agents. Conversely, oxidizing agents accelerated SR Ca(2+) leak and decreased [Ca(2+)](SR) in cells from normal hearts. Moreover, exposure to antioxidants significantly improved intracellular Ca(2+)-handling parameters in intact HF myocytes. Single RyR2 channel activity was significantly higher in HF versus control because of increased sensitivity to activation by luminal Ca(2+) and was partially normalized by reducing agents through restoring luminal Ca(2+) sensitivity oxidation of control RyR2s enhanced their luminal Ca(2+) sensitivity, thus reproducing the HF phenotype. These findings suggest that redox modification contributes to abnormal function of RyR2s in HF, presenting a potential therapeutic target for treating HF.
Does It MEK a Difference? Understanding Immune Effects of Targeted Therapy
Authors: Zachary A. Cooper, Alexandre Reuben, Jacob Austin-Breneman, Jennifer A. Wargo
Journal: Clinical Cancer Research (2015)

Abstract BRAF inhibitor (BRAFi) treatment enhances antitumor immunity, but is associated with increased intratumoral PD-L1 expression. MEK inhibitors (MEKi) may alter T-cell function; however, recent studies demonstrate preserved T-cell infiltrate during treatment with BRAFi/MEKi. These data have important implications for combining BRAFi/MEKi and checkpoint blockade in the treatment of melanoma. Clin Cancer Res; 21(14); 3102–4. ©2015 AACR. See related article by Kakavand et al., p. 3140
Electroconductive Nanopatterned Substrates for Enhanced Myogenic Differentiation and Maturation
Authors: Hee Seok Yang, Bora Lee, Jonathan H. Tsui, Jesse Macadangdang, Seok‐Young Jang, Sung Gap Im, Deok‐Ho Kim
Journal: Advanced Healthcare Materials (2015)

Electrically conductive materials provide a suitable platform for the in vitro study of excitable cells, such as skeletal muscle cells, due to their inherent conductivity and electroactivity. Here it is demonstrated that bioinspired electroconductive nanopatterned substrates enhance myogenic differentiation and maturation. The topographical cues from the highly aligned collagen bundles that form the extracellular matrix of skeletal muscle tissue are mimicked using nanopatterns created with capillary force lithography. Electron beam deposition is then utilized to conformally coat nanopatterned substrates with a thin layer of either gold or titanium to create electroconductive substrates with well‐defined, large‐area nanotopographical features. C2C12 cells, a myoblast cell line, are cultured for 7 d on substrates and the effects of topography and electrical conductivity on cellular morphology and myogenic differentiation are assessed. It is found that biomimetic nanotopography enhances the formation of aligned myotubes and the addition of an electroconductive coating promotes myogenic differentiation and maturation, as indicated by the upregulation of myogenic regulatory factors Myf5 , MyoD , and myogenin ( MyoG ). These results suggest the suitability of electroconductive nanopatterned substrates as a biomimetic platform for the in vitro engineering of skeletal muscle tissue.
The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. I. Proliferative response.
Authors: A S Kong, S I Morse
Journal: The Journal of Experimental Medicine (1977)

The lymphocytosis-promoting factor of Bordetella pertussis is a potent mitogen for murine lymphocytes in vitro. The stimulatory response was not the result of specific antigen stimulation. Spleen and lymph node cells were responsive, whereas normal thymocytes were unresponsive. However, DNA replication was induced in cortisone-resistant thymocytes by lymphocytosis-promoting factor (LPF). Bone marrow cells were not stimulated by LPF.
Does a Low Sodium Diet Improve Asthma Control?
Authors: Zara E. K. Pogson, Marilyn D. Antoniak, Sarah J. Pacey, Sarah A. Lewis, John R. Britton, Andrew W. Fogarty
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Observational studies and initial randomized trials have indicated that a low sodium diet may improve asthma control.Objectives: We tested the hypothesis that a low sodium diet would improve asthma control over a 6-week period.Methods: Participants with a physician diagnosis of asthma and measurable bronchial reactivity to methacholine entered a randomized double-blind placebo-controlled trial. All adopted a low sodium diet and were randomized to receive either 80 mmol/day of oral sodium supplements (normal sodium intake) or matched placebo (low sodium intake) for 6 weeks. The primary outcome was change in bronchial reactivity to methacholine; secondary outcomes were change in lung function, morning and evening peak expiratory flow, asthma symptoms score, daily bronchodilator use, Juniper Standardized Asthma Quality of Life Questionnaire score, and atopy.Measurements and Main Results: A total of 220 individuals entered the study, of whom 199 completed the protocol. In the low sodium–intake group, mean daily urinary sodium excretion decreased by 20 mmol (SD, 64 mmol) and in the normal-sodium-intake group increased by 28 mmol (SD, 74 mmol). There were no differences between the two groups in the primary or secondary outcome measures; the mean difference in bronchial reactivity between the low- and normal-intake groups was −0.03 doubling doses of methacholine (95% confidence interval, −0.60 to 0.53).Conclusions: The use of a low sodium diet as an adjunctive therapy to normal treatment has no additional therapeutic benefit in adults with asthma and bronchial reactivity to methacholine.Clinical trial registered with www.controlled-trials.com (ISRCTN80771653).
Exhaled Breath Condensates: Analyzing the Expiratory Plume
Authors: Richard M. Effros, Richard Casaburi, Janos Porszasz, Edith M. Morales, Virender Rehan
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The mixture of gases and droplets released during exhalation can be hydrodynamically designated as a "plume."Traditionally, pulmonologists focused on respiratory gases in these plumes, but recent identification of biomarkers in exhaled breath condensates (EBCs) has initiated vigorous efforts to harness this simple, noninvasive approach for diagnostic purposes (.700 citations in PubMed since 2000).A typical condenser removes about half of the approximately 45 ml of liquid water that can theoretically be extracted from each liter of saturated exhaled air.Nearly all of this water evaporates from lung surfaces, but approximately 1/10,000 of the condensate (w4.5 nl) represents droplets released from the airway lining fluid (ALF).The assumption that these droplets are released from airways seems justified because alveolar convection is probably negligible and oral contributions can be minimized.ALF droplets can be generated by detachment from airways or rupture of bubbles from previously occluded airways (1), perhaps associated with audible rales.Passage of exhaled air through the mouth at a site near the condenser makes it difficult to avoid contamination of EBC with salivary fluid.To ensure that saliva represents less than 10% of ALF volume, less than 10 nl of saliva should be collected in each milliliter of EBC, a daunting requirement.However, this was successfully accomplished in 36 of 40 samples when the mouthpiece was separated from the condenser, as judged by a sufficiently sensitive amylase assay (2).Nonvolatile biomarkers (e.g., cytokines, ions, and urea) found in EBCs are exclusively derived from ALF droplets (Figure 1) (3-8).Dilution (D) of ALF by water vapor is generally quite variable, but D can be estimated with nonvolatile "dilutional" standard indicators (S), selected to have similar concentrations in ALF and plasma, for example, urea, cations, or conductivity following lyophilization:Lyophilization is used to extract water and volatiles (e.g., NH 3 and CO 2 ) from ice at temperatures below 250 8 C, and should not be confused with centrifugal evaporation at warmer temperatures, which may denature proteins.The EBC samples can be concentrated by reconstituting the dried samples in smaller volumes of pure water.D must be determined before conclusions