tbuckley/cabot-search huggingface dataset:
LSC 2013 abstract - The role of mast cells, IL-13 and TRP channels in a mouse model of chemical-induced airway hyperresponsiveness
Authors: Fien Devos, Vanessa De Vooght, Benoit Nemery, Peter Hoet, Jeroen Vanoirbeek
Journal: European Respiratory Journal (2013)

Occupational asthma is the most common work-related lung disease in industrialized countries. The mechanisms of occupational asthma caused by chemicals are still not completely understood. Therefore, we used a mouse model of chemical-induced asthma to examine the role of the neurogenic system as well as the role of IL-13 and mast cells by using different knock-out mice.

On days 1 and 8, wild type C57Bl/6 mice, IL-13, Transient Receptor Potential (TRP)V1, TRPA1 and mast cell deficient mice were dermally sensitized with 1% toluene-2.4-diisocyanate (TDI) or vehicle (acetone/olive oil) on both ears. On day 15, the mice received a single intranasal challenge with 0.1% TDI or vehicle. In a second experiment TDI or vehicle sensitized wild type C57Bl/6 mice received an intraperitoneal injection of the NK1R antagonist RP67580 (1μg/μl) prior to the challenge. Airway reactivity to methacholine, lung inflammation, lymphocyte subpopulations in the draining auricular lymph nodes and total serum IgE were assessed 24h after the challenge.

IL-13, TRPV1, TRPA1 and mast cell deficient mice showed a significant lower airway hyperreactivity compared to wild type mice, 24h after TDI challenge, without any sign of lung inflammation. Treatment with the NK1R antagonist also resulted in a significant decrease in airway hyperreactivity. In the auricular lymph nodes T-helper cells, T-cytotoxic cells and B-cells were significantly lower in mast cell deficient and IL-13 deficient mice, compared to wild type mice.

These results indicate the importance of IL-13, TRPA1 and TRPV1 channels and mast cells in the development of immune-mediated bronchial hyperreactivity.
Pharmacology of Antagonists of Angiotensin I and II
Authors: PHILIP NEEDLEMAN, EUGENE M. JOHNSON, WILLIAM VINE, EVERETT FLANIGAN, GARLAND R. MARSHALL
Journal: Circulation Research (1972)

The octapeptide analogues 8-Cys-AII, 8-Ile-AII, 4-Phe-8-Tyr-AII, and p -fluoro-4-Phe-AII were potent competitive antagonists of angiotensin I and II (AI and AII) in rat uterus strips, whereas the decapeptide analogues 4-Phe-8-Tyr-AI and 8-Ile-AI were weak antagonists, 8-Cys-AII and 8-Ile-AII were potent antagonists of the rise in blood pressure induced by angiotensin, although 4-Phe-8-Tyr-AII and p -fluoro-4-Phe-AII were less potent antagonists. AI was rapidly converted and was equipotent to AII in vivo, but 8-Ile-AI was a hundred times less potent than 8-Ile-AII. However, some conversion of 8-Ile-AI did occur, since SQ 20881 (an inhibitor of angiotensin-converting enzyme) markedly diminished the All antagonistic action of 8-Ile-AI. The decapeptides AI, 8-Ile-AI, and 4-Phe-8-Tyr-AI were potent competitive antagonists of the hydrolysis of hippurylhistidylleucine by converting enzyme in vitro. Infusion of the octapeptide and the decapeptide angiotensin analogues resulted in a significant lowering of the blood pressure in anesthetized rats treated with phenoxybenzamine and propranolol and made acutely hypertensive by unclamping a renal pedicle that had been temporarily occluded. The decapeptide analogues, therefore, can function as inhibitors of angiotensin-converting enzyme and simultaneously generate octapeptide antagonists in vivo.
MET as a Target in Papillary Renal Cell Carcinoma
Authors: André P. Fay, Sabina Signoretti, Toni K. Choueiri
Journal: Clinical Cancer Research (2014)

The biology underlying papillary renal cell carcinoma (pRCC) is largely unknown, and no specific therapies have been developed for advanced disease. The elucidation of the MET pathway status in types I and II pRCC may help to select patients who are more likely to benefit from MET inhibitors.
Immunochemical Staining With Fluorescein-Labeled Antibodies as an Aid in the Study of Skin Cancer Formation2
Authors: C. Carruthers, A. Baumler
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Immunochemical Staining With Fluorescein-Labeled Antibodies as an Aid in the Study of Skin Cancer Formation Get access C. Carruthers, C. Carruthers Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Baumler A. Baumler Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 34, Issue 2, February 1965, Pages 191–200, https://doi.org/10.1093/jnci/34.2.191 Published: 01 February 1965 Article history Received: 18 June 1964 Published: 01 February 1965
Sicca symptoms, saliva and tear production, and disease variables in 636 patients with rheumatoid arthritis
Authors: T. Uhlig, T. K. Kvien, J. L. Jensen, T. Axell
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVES</h3> (1) To estimate the prevalence of ocular and oral sicca symptoms (SISY) or reduced saliva and tear production; (2) to relate SISY and sicca signs to measures of disease activity, damage, and health status; and (3) to examine the relation between symptoms and objective signs of tear and saliva production in a large sample of representative patients with rheumatoid arthritis (RA). <h3>METHODS</h3> From an unselective county RA register 636 patients (age 20–70 years) were examined with Schirmer-I test (ST), unstimulated whole saliva (UWS), questions on SISY and measures of disease activity, damage and health status. <h3>RESULTS</h3> Ocular sicca symptoms were reported in 38%, oral sicca symptoms in 50%, and a combination of both in 27%. Reduced tear production was present in 29%, and reduced saliva production in 17%. The minimum frequency of secondary Sjögren's syndrome was 7%. Measurements of exocrine disease manifestations were to variable extents bivariately correlated to disease activity measures, physical disability, pain, fatigue, and use of xerogenic drugs, but were not related to deformed joint count. Multivariate analyses revealed significant associations between disease activity and reduced saliva production. Only weak associations between SISY and tear or saliva production were observed. <h3>CONCLUSION</h3> SISY, reduced tear and saliva production were frequent extra-articular manifestations in RA, but were only weakly intercorrelated. High disease activity and at least two SISY were independent predictors of reduced saliva production, but ocular and oral dryness did not seem to be closely related to disease duration, disease activity, damage or health status.
Functional Diversity of Human Protection of Telomeres 1 Isoforms in Telomere Protection and Cellular Senescence
Authors: Qin Yang, Ran Zhang, Izumi Horikawa, Kaori Fujita, Yalda Afshar, Antti Kokko, Päivi Laiho, Lauri A. Aaltonen, Curtis C. Harris
Journal: Cancer Research (2007)

Abstract Protection of telomeres 1 (POT1) proteins in various organisms bind telomeres and regulate their structure and function. In contrast to mice carrying two distinct POT1 genes encoding two POT1 proteins (POT1a and POT1b), humans have the single POT1 gene. In addition to full-length POT1 protein (variant v1), the human POT1 gene encodes four other variants due to alternative RNA splicing (variants v2, v3, v4, and v5), whose functions are poorly understood. The functional analyses of the NH2-terminally and COOH-terminally truncated POT1 variants in this study showed that neither the single-stranded telomere-binding ability of the NH2-terminal oligonucleotide-binding (OB) folds nor the telomerase-dependent telomere elongation activity mediated by the COOH-terminal TPP1-interacting domain was telomere protective by itself. Importantly, a COOH-terminally truncated variant (v5), which consists of the NH2-terminal OB folds and the central region of unknown function, was found to protect telomeres and prevent cellular senescence as efficiently as v1. Our data revealed mechanistic and functional differences between v1 and v5: (a) v1, but not v5, functions through the maintenance of telomeric 3′ overhangs; (b) p53 is indispensable to v5 knockdown-induced senescence; and (c) v5 functions at only a fraction of telomeres to prevent DNA damage signaling. Furthermore, v5 was preferentially expressed in mismatch repair (MMR)-deficient cells and tumor tissues, suggesting its role in chromosome stability associated with MMR deficiency. This study highlights a human-specific complexity in telomere protection and damage signaling conferred by functionally distinct isoforms from the single POT1 gene. [Cancer Res 2007;67(24):11677–86]
Decreased Blood Flow with Increased Metabolic Activity: A Novel Sign of Pancreatic Tumor Aggressiveness
Authors: Gaber Komar, Saila Kauhanen, Kaisa Liukko, Marko Seppänen, Sami Kajander, Jari Ovaska, Pirjo Nuutila, Heikki Minn
Journal: Clinical Cancer Research (2009)

To study blood flow (BF) and metabolism in normal pancreas and in different pancreatic lesions. We then determined the effect of these biomarkers on outcome in patients with pancreatic cancer.Oxygen-15-labeled water and fluorodeoxyglucose positron emission tomography/computed tomography scans were used in 26 patients with a suspicion of pancreatic cancer to measure pancreatic BF and metabolism. In addition, the ratio of standardized uptake value to BF (SUV/BF) was calculated. Patients were divided into three groups: patients with a finding of normal pancreas (n = 7), benign lesions (n = 8), and malignant tumors (n = 11).Patients with benign and malignant pancreatic tumors had decreased BF of the lesion by 48% and 60%, respectively, compared with patients with normal pancreatic tissue. SUV(max) was 3-fold higher in malignant tumors compared with both benign lesions and normal pancreas (P < 0.05). In contrast, the SUV(max) of patients with benign lesions and normal pancreas did not differ. The SUV/BF ratio was significantly higher in malignant lesions than in benign lesions or in patients with normal pancreas (P < 0.05). In patients with cancer, high SUV/BF ratio was a stronger predictor of poor survival compared with high metabolism or lower-than-normal pancreatic BF.BF in pancreatic cancer is significantly reduced compared with the normal pancreas, which may in part explain the poor success of both radiotherapy and chemotherapy. We suggest that the composite measurement of BF and metabolism in pancreatic cancer could serve as a novel tool in the planning of treatments targeting vasculature.
Evaluating and Regulating Lead in Synthetic Turf
Authors: Gregory Van Ulirsch, Kevin Gleason, Shawn Gerstenberger, Daphne B. Moffett, Glenn Pulliam, Tariq Ahmed, Jerald Fagliano
Journal: Environmental Health Perspectives (2010)

In 2007, a synthetic turf recreational field in Newark, New Jersey, was closed because lead was found in synthetic turf fibers and in surface dust at concentrations exceeding hazard criteria. Consequently, public health professionals across the country began testing synthetic turf to determine whether it represented a lead hazard. Currently, no standardized methods exist to test for lead in synthetic turf or to assess lead hazards.Our objectives were to increase awareness of potential lead exposure from synthetic turf by presenting data showing elevated lead in fibers and turf-derived dust; identify risk assessment uncertainties; recommend that federal and/or state agencies determine appropriate methodologies for assessing lead in synthetic turf; and recommend an interim standardized approach for sampling, interpreting results, and taking health-protective actions.Data collected from recreational fields and child care centers indicate lead in synthetic turf fibers and dust at concentrations exceeding the Consumer Product Safety Improvement Act of 2008 statutory lead limit of 300 mg/kg for consumer products intended for use by children, and the U.S. Environmental Protection Agency's lead-dust hazard standard of 40 µg/ft² for floors.Synthetic turf can deteriorate to form dust containing lead at levels that may pose a risk to children. Given elevated lead levels in turf and dust on recreational fields and in child care settings, it is imperative that a consistent, nationwide approach for sampling, assessment, and action be developed. In the absence of a standardized approach, we offer an interim approach to assess potential lead hazards when evaluating synthetic turf.
Prophylactic misuse and recommended use of non-steroidal anti-inflammatory drugs by athletes: Figure 1
Authors: Stuart J Warden
Journal: British Journal of Sports Medicine (2009)

Superstitions and rituals are commonplace in sports and range from simple activities such as each player touching a special inanimate object before entering the field of play to more extreme behaviours such as not washing a uniform or wearing the same underwear during a winning streak. These practices are relatively harmless and may reduce precompetition anxiety, but a concerning ritual that has recently developed in sports is the prophylactic use of non-steroidal anti-inflammatory drugs (NSAIDs).

Athletes have relatively unrestricted access to NSAIDs, as they are readily available over-the-counter preparations and not considered as performance-enhancing drugs by the World Anti-Doping Agency.1 It has been known for some years that athletes are frequent users of NSAIDS,2 with approximately a quarter of athletes competing at the Sydney 2000 Olympic Games reporting NSAID use in the 3 days before random drug testing.3 Such prevalent NSAID use may reflect the physical rigors of elite athletic endeavours, but more recent data suggest athletes misuse their open access to NSAIDs. Tscholl and colleagues4 recently reported in this journal that 23% of top-level male football players used NSAIDs in two out of three matches during the 2002 and 2006 …
Insulin-Like Growth Factor-I Regulates Proliferation and Osteoblastic Differentiation of Calcifying Vascular Cells via Extracellular Signal-Regulated Protein Kinase And Phosphatidylinositol 3-Kinase Pathways
Authors: Kristen Radcliff, Tri-Bang Tang, Jina Lim, Zina Zhang, Moeen Abedin, Linda L. Demer, Yin Tintut
Journal: Circulation Research (2005)

Vascular calcification develops within atherosclerotic lesions and results from a process similar to osteogenesis. One of the paracrine regulators of bone-derived osteoblasts, insulin-like growth factor-I (IGF-I), is also present in atherosclerotic lesions. To evaluate its possible role in vascular calcification, we assessed its in vitro effects on proliferation and differentiation in calcifying vascular cells (CVCs), a subpopulation of bovine aortic medial cells. Results showed that IGF-I inhibited spontaneous CVC differentiation and mineralization as evidenced by decreased alkaline phosphatase (AP) activity and decreased matrix calcium incorporation, respectively. Furthermore, IGF-I inhibited the AP activity induced by bacterial lipopolysaccharide, TNF-α, or H 2 O 2 . It also induced CVC proliferation based on 3 H-thymidine incorporation. Results from Northern analysis and tests using IGF-I analogs suggest that IGF-I effects are mediated through the IGF-I receptor. IGF-I also activated both the extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) pathways. Inhibition of either the ERK or PI3K pathway reversed IGF-I effects on CVC proliferation and AP activity, suggesting a common downstream target. Overexpression of ERK activator also mimicked IGF-I inhibition of lipopolysaccharide-induced AP activity. These results suggest that IGF-I promotes proliferation and inhibits osteoblastic differentiation and mineralization of vascular cells via both ERK and PI3K pathways.
Genetic heterogeneity and differences in glomerular hemodynamics between inbred colonies of Munich-Wistar rats.
Authors: F J Fenoy, E St Lezin, T W Kurtz, R J Roman
Journal: Journal of the American Society of Nephrology (1992)

DNA fingerprint analysis and renal micropuncture studies were performed in Munich-Wistar rats purchased from Harlan Industries and Simonsen Laboratories to determine whether these rats are genetically heterogeneous and exhibit differences in glomerular hemodynamics. RBF and GFR were similar in rats from both colonies. Glomerular capillary pressure was lower in rats from the Harlan colony (46 +/- 2 mm Hg) than in those from the Simonsen colony (56 +/- 2 mm Hg). The low glomerular capillary pressure in the Harlan rats was primarily due to a lower postglomerular vascular resistance. The estimated whole-kidney ultrafiltration coefficient (Kf) was significantly greater in the rats obtained from the Harlan colony than in those obtained from the Simonsen colony (0.12 +/- 0.03 versus 0.05 +/- 0.01 mL/min/g kidney wt/mm Hg). The DNA fingerprints of the Simonsen rats were different from those of the Harlan rats. These results provide evidence of physiologic and genetic heterogeneity between commercially available inbred strains of Munich-Wistar rats in the United States and suggest that comparison of results with Munich-Wistar rats from different sources may be more difficult than previously recognized.
A Mediterranean-style, low–glycemic-load diet decreases atherogenic lipoproteins and reduces lipoprotein (a) and oxidized low-density lipoprotein in women with metabolic syndrome
Authors: Jennifer L. Jones, Michael Comperatore, Jacqueline Barona, Mariana C. Calle, Catherine Andersen, Mark McIntosh, Wadie Najm, Robert H. Lerman, Maria Luz Fernandez
Journal: Metabolism (2011)
U6 snRNA Pseudogenes: Markers of Retrotransposition Dynamics in Mammals
Authors: Aurélien J. Doucet, Gaëtan Droc, Oliver Siol, Jérôme Audoux, Nicolas Gilbert
Journal: Molecular Biology and Evolution (2015)

Transposable elements comprise more than 45% of the human genome and long interspersed nuclear element 1 (LINE-1 or L1) is the only autonomous mobile element remaining active. Since its identification, it has been proposed that L1 contributes to the mobilization and amplification of other cellular RNAs and more recently, experimental demonstrations of this function has been described for many transcripts such as Alu, a nonautonomous mobile element, cellular mRNAs, or small noncoding RNAs. Detailed examination of the mobilization of various cellular RNAs revealed distinct pathways by which they could be recruited during retrotransposition; template choice or template switching. Here, by analyzing genomic structures and retrotransposition signatures associated with small nuclear RNA (snRNA) sequences, we identified distinct recruiting steps during the L1 retrotransposition cycle for the formation of snRNA-processed pseudogenes. Interestingly, some of the identified recruiting steps take place in the nucleus. Moreover, after comparison to other vertebrate genomes, we established that snRNA amplification by template switching is common to many LINE families from several LINE clades. Finally, we suggest that U6 snRNA copies can serve as markers of L1 retrotransposition dynamics in mammalian genomes.
NF-κB–Inhibited Acute Myeloid Leukemia Cells Are Rescued from Apoptosis by Heme Oxygenase-1 Induction
Authors: Stuart A. Rushworth, Kristian M. Bowles, Prahlad Raninga, David J. MacEwan
Journal: Cancer Research (2010)

Despite high basal NF-kappaB activity in acute myeloid leukemia (AML) cells, inhibiting NF-kappaB in these cells has little or no effect on inducing apoptosis. We previously showed that heme oxygenase-1 (HO-1) underlies this resistance of AML to tumor necrosis factor-induced apoptosis. Here, we describe a mechanism by which HO-1 is a silent antiapoptotic factor only revealed when NF-kappaB is inhibited, thus providing a secondary antiapoptotic mechanism to ensure AML cell survival and chemoresistance. We show that inhibition of NF-kappaB increased HO-1 expression in primary AML cells compared with that of nonmalignant cells. In addition, we observed this suppressed HO-1 level in AML cells compared with CD34(+) nonmalignant control cells. Using chromatin immunoprecipitation assay and small interfering RNA knockdown, we showed that the NF-kappaB subunits p50 and p65 control this suppression of HO-1 in AML cells. Finally, we showed that inhibition of HO-1 and NF-kappaB in combination significantly induced apoptosis in AML cells but not in noncancerous control cells. Thus, NF-kappaB inhibition combined with HO-1 inhibition potentially provides a novel therapeutic approach to treat chemotherapy-resistant forms of AML.
Gallium-transferrin binding in Alzheimer disease
Authors: J.M Candy, C.M Morris, G.A Taylor, J.A Edwardson, J.G Joshi, HerbertM Schulman, Prem Ponka, J.C.M Spear, Paul Altmann, Gillian Farrar, Simon Welch, JohnA Blair
Journal: The Lancet (1990)
Bilirubin inhibits bile acid induced apoptosis in rat hepatocytes
Authors: A Granato
Journal: Gut (2003)

Hydrophobic bile acids contribute to hepatocellular injury in cholestasis and rapidly induce apoptosis in vitro; however, unlike Fas agonists, cholestasis does not cause extensive hepatocyte apoptosis. As antioxidants provide protection against bile acid induced liver injury, our premise was that bilirubin, a free radical scavenger with increased plasma levels in the presence of liver disease, could protect hepatocytes against bile acid induced apoptosis.Freshly isolated rat hepatocytes were incubated for four hours with 100 micromol/l glycochenodeoxycholate (GCDC) alone or with increasing concentrations of unconjugated (UCB) or conjugated (CB) bilirubin.Both UCB and CB inhibited GCDC induced apoptosis in a dose dependent fashion and suppressed the generation of reactive oxygen species by hepatocytes.The antiapoptotic effect of bilirubin associated with its antioxidant properties indicates that hyperbilirubinaemia may have a protective role in liver disease.
Health status of patients with ankylosing spondylitis: a comparison with the general population
Authors: H. Dagfinrud, A. M. Mengshoel, K. B. Hagen, Jon Havard Loge, T. K. Kvien
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To examine the subjective health in patients with ankylosing spondylitis (AS) compared with the general population, and to explore the associations between health status and age, sex of the patients, and educational level in AS. <b>Methods:</b> Health status was assessed with a generic instrument (SF-36) in 314 patients with AS and in 2323 people from the general population. Subgroup analyses were performed according to age, sex, and educational level. Standard difference scores (s-scores) were calculated to ensure the clinical meaningfulness of the norm based comparisons. <b>Results:</b> Both men and women with AS reported significantly impaired health on all scales of the SF-36. Women reported significantly worse health on physical health domains. However, when calculating differences from the general population, numerically larger s-scores were found for men (except for physical role and vitality). The relative impact of AS seems to diminish with increasing age. In AS, better health was significantly associated with higher education across all scales. Deviations from the general population on the non-physical health aspects were especially pronounced in patients with low education. <b>Conclusions:</b> All key dimensions of health are affected by AS. The physical aspects seem to be most severely affected, but in the less educated group of patients, the disease impact on the mental health aspects was also considerable. Evaluation and management planning should take the complexity of AS into consideration. The focus on physical function should be maintained, and additional attention should be paid to the mental and social consequences of AS.