tbuckley/cabot-search huggingface dataset:
Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively regulates angiogenesis
Authors: Céline Sabatel, Anne M Cornet, Sébastien P Tabruyn, Ludovic Malvaux, Karolien Castermans, Joseph A Martial, Ingrid Struman
Journal: Molecular Cancer (2010)

Abstract Background Disorganized angiogenesis is associated with several pathologies, including cancer. The identification of new genes that control tumor neovascularization can provide novel insights for future anti-cancer therapies. Sprouty1 (SPRY1) , an inhibitor of the MAPK pathway, might be one of these new genes. We identified SPRY1 by comparing the transcriptomes of untreated endothelial cells with those of endothelial cells treated by the angiostatic agent 16 K prolactin (16 K hPRL). In the present study, we aimed to explore the potential function of SPRY1 in angiogenesis. Results We confirmed 16 K hPRL induced up-regulation of SPRY1 in primary endothelial cells. In addition, we demonstrated the positive SPRY1 regulation in a chimeric mouse model of human colon carcinoma in which 16 K hPRL treatment was shown to delay tumor growth. Expression profiling by qRT-PCR with species-specific primers revealed that induction of SPRY1 expression by 16 K hPRL occurs only in the (murine) endothelial compartment and not in the (human) tumor compartment. The regulation of SPRY1 expression was NF-κB dependent. Partial SPRY1 knockdown by RNA interference protected endothelial cells from apoptosis as well as increased endothelial cell proliferation, migration, capillary network formation, and adhesion to extracellular matrix proteins. SPRY1 knockdown was also shown to affect the expression of cyclinD1 and p21 both involved in cell-cycle regulation. These findings are discussed in relation to the role of SPRY1 as an inhibitor of ERK/MAPK signaling and to a possible explanation of its effect on cell proliferation. Conclusions Taken together, these results suggest that SPRY1 is an endogenous angiogenesis inhibitor.
A shared transcriptional program in early breast neoplasias despite genetic and clinical distinctions
Authors: Alayne L Brunner, Jun Li, Xiangqian Guo, Robert T Sweeney, Sushama Varma, Shirley X Zhu, Rui Li, Robert Tibshirani, Robert B West
Journal: Genome biology (2014)

Abstract Background The earliest recognizable stages of breast neoplasia are lesions that represent a heterogeneous collection of epithelial proliferations currently classified based on morphology. Their role in the development of breast cancer is not well understood but insight into the critical events at this early stage will improve efforts in breast cancer detection and prevention. These microscopic lesions are technically difficult to study so very little is known about their molecular alterations. Results To characterize the transcriptional changes of early breast neoplasia, we sequenced 3′- end enriched RNAseq libraries from formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched normal breast and carcinoma samples from 25 patients. We find that gene expression patterns within early neoplasias are distinct from both normal and breast cancer patterns and identify a pattern of pro-oncogenic changes, including elevated transcription of ERBB2 , FOXA1 , and GATA3 at this early stage. We validate these findings on a second independent gene expression profile data set generated by whole transcriptome sequencing. Measurements of protein expression by immunohistochemistry on an independent set of early neoplasias confirms that ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently upregulated at this early stage. The early neoplasia samples also demonstrate coordinated changes in long non-coding RNA expression and microenvironment stromal gene expression patterns. Conclusions This study is the first examination of global gene expression in early breast neoplasia, and the genes identified here represent candidate participants in the earliest molecular events in the development of breast cancer.
High peptic stricture of the oesophagus.
Authors: J S Davidson
Journal: Thorax (1976)

Fifty-seven patients with high peptic stricture and the lower oesophagus lined by columnar epithelium are considered from the clinical point of view. Information from 115 cases of low stricture is introduced for comparison. The average age of adult patients was 62 years with a sex incidence of 36 females to 21 males. There is little difference between the symptoms of high and low strictures. Radiologically, the majority of high strictures are short and smooth but other types are illustrated. Carcinoma and congenital mid-oesophageal web are considered in the differential diagnosis. There was an associated duodenal ulcer in 10% of cases. In six patients, a high stricture developed soon after an abdominal operation or period of recumbency. Two patients are illustrated showing the process of stricture formation. Four patients are described who had gastric-lined oesophagus but no ulceration of stricture. One patient had a Barrett ulcer in addition to a high stricture. A patient is described in whom the mucosa of the lower oesophagus appeared to be replaced by jejunal mucosa following oesophagojejunostomy. One patient is illustrated in whom a stricture was seen to ascend the oesophagus over a period of six years. Thirty-three patients were treated by dilatation and 24 by operation. Hernial repair is an effective form of treatment. Of 19 patients treated in this way, significant dysphagia persisted in two and slight dysphagia in one. The clinical findings are discussed in relation to the origin of columnar epithelium in the oesophagus.
The prevalence of musculoskeletal injuries in runners: a systematic review
Authors: L C Hespanhol Junior, A C A Carvalho, L O P Costa, A D Lopes
Journal: British Journal of Sports Medicine (2011)

Background The number of runners worldwide is large and still growing, and in the last 30 years the number of publications on running-related injuries has grown substantially. Many of these studies indicate the total rate of injuries and the most frequently injured body parts, but it is not describe what the injuries are. Objective To summarise the literature that focused on the most prevalent musculoskeletal running-related injuries. Design A systematic review. Setting The articles are related with long-distance runners without restriction of competitive level. Interventions Searches were performed on MEDLINE, PEDro, LILACS and SCIELO. The keywords and operands used were: sport AND injuries AND running. There was no restriction with regards to the publication date. This search is updated up to September 2010. Main outcome measurements We extracted the following data from the selected papers: year of publication, authors, purpose of the study, study population characteristics, study design, which musculoskeletal running-related injuries was more frequent and the anatomical location of these injuries. Results Of 2043 found studies, 1767 were excluded by title, 153 were excluded after reading the abstract and 114 were excluded after reading the full report. Nine articles were considered eligible and therefore were included. The five most frequently running-related injuries found in the retrieved nine studies were the Patellofemoral Syndrome, Achilles Tendinopathy, Iliotibial Band Syndrome, Plantar Fasciitis and Tibial Stress Syndrome. The remaining injuries did not have their frequency sets well established. Conclusion The most frequent running-related injury among long distance runners are the Patellofemoral Syndrome, followed by Achilles Tendinopathy, Iliotibial Band Syndrome and Plantar Fasciitis. We suggest that more prospective follow-up studies should be conducted and present their data through scoring injury per hours of running exposure.
Colour perception may optimize biologically relevant surface discriminations – rather than type-I constancy
Authors: Nicola Bruno, Stephen Westland
Journal: Behavioral and Brain Sciences (2001)

Trichromacy may result from an adaptation to the regularities in terrestrial illumination. However, we suggest that a complete characterization of the challenges faced by colour perception must include changes in surface surround and illuminant changes due to inter-reflections between surfaces in cluttered scenes. Furthermore, our trichromatic system may have evolved to allow the detection of brownish-reddish edibles against greenish backgrounds. [Shepard]
Physicochemical evaluation and in vitro release studies on itraconazolium sulfate salt
Authors: Neeraj Kumar, Shishu Goindi, Gulshan Bansal
Journal: Asian Journal of Pharmaceutical Sciences (2013)

To counter the poor aqueous solubility of itraconazole (ITC), its sulfate salt (ITCSUL) was synthesized and characterized by 1H NMR, MS, FTIR, DSC, XRPD, DLS and SEM. Antifungal properties of ITCSUL were confirmed against different fungal pathogens by broth microdilution method. Enhanced solubility of the salt in various pharmaceutical solvents was observed. Approximately 5.5 fold increase in percentage drug release from ITCSUL than that of ITC in 3 h was observed. Further, the physical mixtures of ITCSUL with two cyclodextrins; β-cyclodextrin (β-CD) and HP-β-cyclodextrin (HP-β-CD) were prepared in 3 M ratios. The in vitro release studies of CD mixtures of ITC and ITCSUL exhibited markedly enhanced dissolution in comparison to ITC and ITCSUL respectively. The promising in vitro performance of ITCSUL and ITCSUL CD mixtures along with advantage of expedient preparation suggest their potential applications in designing a better oral drug delivery system.
Kinase-Impaired <i>BRAF</i> Mutations in Lung Cancer Confer Sensitivity to Dasatinib
Authors: Banibrata Sen, Shaohua Peng, Ximing Tang, Heidi S. Erickson, Hector Galindo, Tuhina Mazumdar, David J. Stewart, Ignacio Wistuba, Faye M. Johnson
Journal: Science Translational Medicine (2012)

Induction of tumor cell senescence may explain the response of a patient with BRAF kinase–impaired lung cancer to the multikinase inhibitor dasatinib.
Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease
Authors: Norbert Hubner, Caroline A Wallace, Heike Zimdahl, Enrico Petretto, Herbert Schulz, Fiona Maciver, Michael Mueller, Oliver Hummel, Jan Monti, Vaclav Zidek, Alena Musilova, Vladimir Kren, Helen Causton, Laurence Game, Gabriele Born, Sabine Schmidt, Anita Müller, Stuart A Cook, Theodore W Kurtz, John Whittaker, Michal Pravenec, Timothy J Aitman
Journal: Nature Genetics (2005)
Enhanced Antitumor Efficacy of a DR5-Specific TRAIL Variant over Recombinant Human TRAIL in a Bioluminescent Ovarian Cancer Xenograft Model
Authors: Evelien W. Duiker, Elisabeth G.E. de Vries, Devalingam Mahalingam, Gert Jan Meersma, Wytske Boersma-van Ek, Harry Hollema, Marjolijn N. Lub-de Hooge, Go M. van Dam, Robbert H. Cool, Wim J. Quax, Afshin Samali, Ate G.J. van der Zee, Steven de Jong
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) is clinically evaluated as novel anticancer drug. rhTRAIL-DR5, a rhTRAIL variant that specifically binds to DR5 receptor, has recently been developed. We investigated whether rhTRAIL-DR5 is more efficient than rhTRAIL in combination with cisplatin in DR5-expressing human A2780 ovarian cancer cells. Design: Effect of cisplatin alone or in combination with rhTRAIL or rhTRAIL-DR5 on DR5 surface expression, apoptosis, and cell survival of A2780 was measured. Biodistribution analysis was done in mice with 125I-rhTRAIL administered intravenously versus intraperitoneally. Antitumor efficacy of rhTRAIL-DR5 versus rhTRAIL was determined in an intraperitoneally growing bioluminescent A2780 xenograft model. Results: Cisplatin strongly enhanced DR5 surface expression. Both rhTRAIL and rhTRAIL-DR5 in combination with cisplatin induced high levels of caspase-3 activation, apoptosis, and cell kill, with rhTRAIL-DR5 being most potent. Intraperitoneal administration of 125I-rhTRAIL resulted in a 1.7-fold higher area under the curve in serum, increased tumor exposure, and more caspase-3 activation in the tumor than intravenous administration. Intraperitoneal administration of rhTRAIL-DR5 delayed A2780 tumor progression, reflected in a mean light reduction of 68.3% (P = 0.015), whereas rhTRAIL or rhTRAIL-DR5 plus cisplatin resulted in 85% (P = 0.003) and 97% (P = 0.002) reduction compared with A2780 tumor progression in vehicle-treated animals. Combination of rhTRAIL-DR5 with cisplatin was more effective than cisplatin alone (P = 0.027). Conclusion: rhTRAIL-DR5 was superior over rhTRAIL in vitro and in vivo against DR5-expressing ovarian cancer also in combination with cisplatin. Intraperitoneal administration of rhTRAIL-DR5 warrants further exploration in ovarian cancer.
Mycobacterial aetiology of Crohn's disease: serologic study using common mycobacterial antigens and a species-specific glycolipid antigen from Mycobacterium paratuberculosis.
Authors: S N Cho, P J Brennan, H H Yoshimura, B I Korelitz, D Y Graham
Journal: Gut (1986)

Crohn9s disease is a granulomatous form of enteritis superficially similar to Johne9s disease (paratuberculosis) of ruminants. Recently, a Mycobacterium sp closely related to Mycobacterium paratuberculosis was cultured from tissues of patients with Crohn9s disease suggesting that M paratuberculosis may be the aetiologic agent in some cases. In addition, greater seroreactivity to M paratuberculosis has been reported in patients with Crohn9s disease. In the present study, we have evaluated the serum antibody response to disrupted M paratuberculosis using ELISA and serum specimens from 33 people with Crohn9s disease, 21 with ulcerative colitis, and 12 non-inflammatory bowel disease controls. We failed to find a consistent IgG, IgM, or IgA antibody response to Mycobacterium paratuberculosis. The results indicate that, as in bovine paratuberculosis, serum seroreactivity is not a reliable tool for examining the relationship between human intestinal disease and mycobacteria.
Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study
Authors: Raquel Granell, A. John Henderson, David M. Evans, George Davey Smith, Andrew R. Ness, Sarah Lewis, Tom M. Palmer, Jonathan A. C. Sterne
Journal: PLoS Medicine (2014)

Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach.We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-values<0.001) and with childhood asthma (RR 2.56, 95% CI 1.38-4.76 per unit score, p = 0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (95% CI 1.16-2.07) per kg/m2, p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19-3.03) than for atopic asthma (1.37, 95% CI 0.89-2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11-1.79) per 0.5 kg and 2.25 (95% CI 1.23-4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects.Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century. Please see later in the article for the Editors' Summary.
Induction of Heme-oxygenase-1 Prevents the Systemic Responses to Hemorrhagic Shock
Authors: FABIENNE TAMION, VINCENT RICHARD, GUY BONMARCHAND, JACKY LEROY, JEAN-PIERRE LEBRETON, CHRISTIAN THUILLEZ
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Oxidant-mediated reperfusion injury of the gut is a major contributor of the systemic inflammatory response in hemorrhagic shock. Recent studies have suggested that heme-oxygenase-1 (HO-1) represents an endogenous protective mechanism against oxidant stress. We assessed whether HO-1 induction modulates the synthesis of tumor necrosis factor-alpha (TNF-alpha) in hemorrhagic shock. In rats submitted to hemorrhagic shock, pretreatment with hemoglobin (Hb) increased HO-1 mRNA expression in macrophages. This increased expression was associated with a decreased expression of TNF-alpha mRNA, as well as decreased plasma concentrations of TNF-alpha. These effects of Hb were reduced by the HO-1 inhibitor tin-protoporphyrin (Sn-PP 20 micromol/kg), while Sn-PP had no effect in the absence of Hb. In parallel, Hb pretreatment reduced pulmonary edema, vascular injury, and increased mesenteric blood flow, and these effects were reduced by Sn-PP. Thus, induction of HO-1 is protective in hemorrhagic shock, possibly through its antioxidant properties. Interventions that induce HO-1 may be beneficial in the treatment of shock states, leading to a reduced systemic inflammatory response.
Oxidized BAL fluid proteins in patients with interstitial lung diseases
Authors: AG Lenz, U Costabel, KL Maier
Journal: European Respiratory Journal (1996)

Oxygen-derived free radicals, released by phagocytic cells, have been postulated to contribute to lung tissue damage. We therefore investigated oxidative damage to proteins from bronchoalveolar lavage fluid (BALF) as an indicator of oxidative stress and to assess antioxidant defences in the lungs. We examined BAL fluids from patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF, nonsmokers (NS) and smokers (S)), sarcoidosis (SARC, nonsmokers), and asbestosis (ASB, ex-smokers (EXS)). The oxidation of BALF proteins is accompanied by the introduction of carbonyl groups into their amino acid side-chains and can be quantitated by labeling these groups with tritiated borohydride. The total lung content of oxidized proteins recovered by bronchoalveolar lavage (BAL) was 0.3 +/- 0.07 nmol carbonyl.mL-1 BALF (mean +/- SEM) in the NS control group (n = 9) and tended to be increased, in the asymptomatic S group (n = 8; 0.59 +/- 0.14 nmol.mL-1). This parameter was significantly elevated both in IPF-NS (n = 14; 0.84 +/- 0.2 nmol carbonyl.mL-1 BALF) and SARC-NS (n = 15; 0.73 +/- 0.16 nmol.mL-1) as compared with the NS control. On the contrary, in smoking patients with IPF (n = 6; 0.41 +/- 0.1 nmol carbonyl.mL-1 BALF) and also in ASB-EXS (n = 6; 0.37 +/- 0.06 nmol.mL-1) it was not different from NS controls. The total amount of oxidized proteins correlated positively with the absolute number of eosinophils (EOS) in IPF-NS, IPF-S and SARC, and also with absolute polymorphonuclear neutrophil (PMN) numbers in IPF-NS and IPF-S. In conclusion, oxidative damage of BALF proteins occurred in nonsmoking patients with IPF and SARC. The amount of oxidized bronchoalveolar lavage fluid protein may provide a quantitative assessment of oxygen burden, a balance between oxidant stress and antioxidant defences.
Mesenchymal cystic hamartoma of the lung: a rare cause of relapsing pneumothorax
Authors: R J van Klaveren, H H M Hassing, J M Wiersma-van Tilburg, L K Lacquet, A L Cox
Journal: Thorax (1994)

A 14 year old boy is described with recurrent spontaneous pneumothoraces due to a mesenchymal cystic hamartoma, a very rare disease with a multicentric nature and a benign course in most patients.
Responsiveness of different multidimensional severity indices to pulmonary rehabilitation in patients with COPD
Authors: Rafael Mesquita, Nidia Aparecida Hernandes, Thaís Sant'Anna, Vanessa Suziane Probst, Fábio Pitta
Journal: European Respiratory Journal (2012)

Background: Multidimensional indices have been used to assess disease severity in patients with COPD. The responsiveness of these indices to pulmonary rehabilitation (PR) needs to be better investigated. Objective: To evaluate the responsiveness of five multidimensional severity indices to PR in patients with COPD. Methods: 35 patients with COPD (17 men, 66±8 years, FEV1 43±16%pred) participated in a PR program of high-intensity endurance and strength training during 3 months. Demographic data, lung function (spirometry), exercise capacity (six-minute walking test [6MWT] and incremental shuttle walking test [ISWT]), dyspnea (Medical Research Council [MRC] scale) and quality of life (Saint George Respiratory Questionnaire [SGRQ]) were assessed before and after the program, and the following indices were calculated: BODE, SAFE, updated BODE (upBODE), ADO and i-BODE. Results: Age, distance walked in the 6MWT and SGRQ score were the only components of the indices which changed after PR (p<0.05 for all). Table 1 summarizes the responsiveness of the indices to PR.

View this table:

Table 1





The percentage of subjects that decreased their score (i.e., improvement) in the BODE, SAFE, upBODE, ADO and i-BODE was 23%, 49%, 23%, 20% and 23%, respectivelly (p>0.05). Conclusions: These preliminary findings indicate that the severity indices evaluated in patients with COPD in this study present very modest responsiveness to pulmonary rehabilitation, despite the improvement in some of its components.
Lung function prior to viral lower respiratory tract infections in prematurely born infants
Authors: S. B. Drysdale, T. Wilson, M. Alcazar, S. Broughton, M. Zuckerman, M. Smith, G. F. Rafferty, S. L. Johnston, A. Greenough
Journal: Thorax (2011)

<h3>Objective</h3> Prematurely born infants who develop respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) have lung function abnormalities at follow-up. The aim of this study was to determine whether prematurely born infants who developed symptomatic RSV, or other viral LRTI(s), had poorer premorbid lung function than infants who did not develop LRTIs during the RSV season. <h3>Methods</h3> Lung function (functional residual capacity (FRC), compliance (Crs) and resistance (Rrs) of the respiratory system) was measured at 36 weeks postmenstrual age. After neonatal unit discharge, nasopharyngeal aspirates were obtained whenever the infants had an LRTI, regardless of whether this was in the community or in hospital. Nasopharyngeal aspirates were examined for RSV A and B, rhinovirus, influenza A and B, parainfluenza 1, 2 and 3, human metapneumovirus and adenovirus. <h3>Results</h3> 159 infants with a median gestational age of 34 (range 23–36) weeks were prospectively followed. 73 infants developed LRTIs: 27 had at least one RSV LRTI and 31 had at least one other viral LRTI, but not an RSV LRTI. Overall, there were no significant differences in the FRC (p=0.54), Crs (p=0.11) or Rrs (p=0.12) results between those who developed an RSV or other viral LRTI and those who did not develop an LRTI. Infants with RSV or other viral LRTIs who were admitted to hospital compared with those who were not had higher Rrs results (p=0.033 and p=0.039, respectively). <h3>Conclusion</h3> Diminished premorbid lung function may predispose prematurely born infants to severe viral LRTIs in infancy.