tbuckley/cabot-search huggingface dataset:
14-3-3σ Expression Is an Independent Prognostic Parameter for Poor Survival in Colorectal Carcinoma Patients
Authors: Alexander Perathoner, Daniela Pirkebner, Gerald Brandacher, Gilbert Spizzo, Sylvia Stadlmann, Peter Obrist, Raimund Margreiter, Albert Amberger
Journal: Clinical Cancer Research (2005)

Abstract Purpose: 14-3-3σ is an intracellular, dimeric, phosphoserine binding protein that is expressed in epithelial cells and involved in cancer development. In this study, we examined the expression of 14-3-3σ and evaluated its clinical significance in colorectal carcinoma. Experimental Design: Expression of 14-3-3σ was analyzed by Western blot in nine colorectal carcinoma cell lines, eight paired colorectal carcinoma tissues, and normal mucosas. Immunohistochemistry was used to evaluate expression of 14-3-3σ in tissues of 121 colorectal carcinoma patients and to correlate it with clinical parameters. Results: Western blot analysis of colorectal carcinoma cell lines and tissues revealed strong 14-3-3σ expression in four of eight cell lines and 14-3-3σ overexpression in carcinomas compared with normal mucosa in six of eight colorectal carcinoma tissue pairs. Immunohistochemical analysis revealed 14-3-3σ overexpression in 38.8% of colorectal carcinoma samples. Furthermore, highly positive immunoreactivity was significantly correlated with tumor differentiation (P &amp;lt; 0.001) and pT stage (P &amp;lt; 0.003). In Kaplan-Meier analysis, 14-3-3σ overexpression was associated with a significantly decreased survival time compared with negatively stained or low stained cases (P &amp;lt; 0.0096). In multivariate regression analysis, 14-3-3σ expression emerged as a significant independent parameter (P &amp;lt; 0.037). Conclusions: These results provide evidence that 14-3-3σ expression increases during carcinoma progression in a subset of colorectal carcinoma. The overexpression of this antigen identifies patients at high risk. It is tempting to suggest that 14-3-3σ overexpression either promotes tumor proliferation and/or prevents apoptotic signal transduction in colorectal carcinoma. Thus, targeting 14-3-3σ might be a new therapeutic strategy in colorectal carcinoma.
Independent task force unveils five year plan to overhaul cancer services in England
Authors: Jacqui Wise
Journal: BMJ (2015)

An extra 30 000 patients could survive cancer for 10 years or more by 2020 if a new five year strategy was fully implemented in England, says an independent cancer task force. Of these patients, around 11 000 would survive longer through earlier diagnosis.

The task force, established by NHS England in January 2015, has set out six strategic priorities, including an emphasis on prevention and a renewed focus on early diagnosis.1 It said that the recommendations would cost an estimated £400m (€570m; $620m) a year but that investment in these initiatives would permit savings in coming years.

The wide ranging 90 page report calls for Public Health England to work with the government to improve public health. It calls for a new tobacco control strategy in …
Surveillance of antituberculosis drug resistance in Switzerland 1995–1997: the central link
Authors: P. Helbling, E. Altpeter, P-A Raeber, G.E Pfyffer, J-P Zellweger
Journal: European Respiratory Journal (2000)

The purpose of the present paper is to investigate the usefulness of routine notification of antituberculosis drug susceptibilities. In Switzerland, laboratories have to report susceptibilities to isoniazid, rifampicin, ethambutol, and pyrazinamide to the Federal Office of Public Health. All clinical and laboratory information on every single tuberculosis case is routinely linked. Proportions of drug resistance were calculated and logistic regression was applied to evaluate the role of potential risk factors. Eighty percent (1056) of all culture-positive tuberculosis cases reported between October 1995 and December 1997 were analysed. The strains of 66 (6.3%) patients had resistances to at least one drug. Risk factors identified were previous antituberculosis treatment (adjusted odds ratio 7.3, 95% confidence interval 3.9-13.6), male sex (1.4, 1.1-2.0), and age <65 yrs (1.5, 1.0-2.3). Fourteen cases (1.3%), 13 of them foreign-born, were resistant to at least isoniazid and rifampicin. Reporting of drug susceptibilities allows routine assessment of the proportion of drug resistant tuberculosis and populations at risk. This proportion was found to be small in Switzerland. Risk factors were previous treatment for tuberculosis, male sex, and age <65 yrs. Resistance to at least isoniazid and rifampicin was predominantly found in foreign-born patients.
Fibers From Disposable Gowns and Drapes
Authors: G. Phelps Dash
Journal: JAMA (1979)

To the Editor.—  As an epidemiologist, I question several conclusions Dr Dragan drew:   Dr Dragan states that there was a rise in postoperative morbidity during the 18-month use of disposable paper gowns and drapes in his hospital; however, he does not state what the incidence of postoperative morbidity was prior to that 18-month period. Was there any statistically significant difference?  No mention of any control group was made in this study.  No classification or cohorting of patients was done as to age, underlying disease, or type of surgery.  There were a variety of complications listed—everything from keloids to intestinal obstruction. Dr Dragan stated that he was able to achieve a positive fiber (wood) identification in only eight of the cases.   Based on Dr Dragan's statistics regarding about 1,000 surgical procedures during which disposables were used, the incidence of postoperative morbidity in these patients was 0.8%;
Effect of oral bronchodilators on lung mucociliary clearance during sleep in patients with asthma.
Authors: A Hasani, J E Agnew, D Pavia, H Vora, S W Clarke
Journal: Thorax (1993)

BACKGROUND: Lung mucociliary clearance rates are reduced during sleep in patients with asthma. Methylxanthines and beta 2 agonists have been shown to enhance rates of lung mucociliary clearance. This study examined whether oral slow release bronchodilators may also have an effect on this clearance mechanism during sleep in patients with asthma. METHODS: Nine patients with asthma with a mean(SE) age of 65(5) years and percentage predicted forced expiratory volume in one second (FEV1 of 61(9)% participated in a double blind, placebo controlled, within subject crossover study to assess the effect of two weeks of treatment with salbutamol (Volmax; 8 mg twice daily) or theophylline (Phyllocontin; 350 mg twice daily) on lung mucociliary clearance during sleep. Lung mucociliary clearance rates were measured by a radioaerosol technique. RESULTS: The observation period for radioaerosol clearance was approximately 0.3 hours before sleep, 6.0 hours during sleep and 0.6 hours after sleep. Mean mucociliary clearance rates for theophylline, placebo and salbutamol before sleep were: 39, 39, and 32%/hour respectively; during sleep: 11, 10, and 9%/hour respectively; and after sleep: 39, 32, and 35%/hour respectively. CONCLUSION: During sleep lung mucociliary clearance in stable asthma was reduced, which is in agreement with the group9s previous findings. Treatment with controlled/slow release oral bronchodilators had no effect on this reduced rate of clearance associated with sleep.
Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population
Authors: Jing Dong, Zhibin Hu, Chen Wu, Huan Guo, Baosen Zhou, Jiachun Lv, Daru Lu, Kexin Chen, Yongyong Shi, Minjie Chu, Cheng Wang, Ruyang Zhang, Juncheng Dai, Yue Jiang, Songyu Cao, Zhenzhen Qin, Dianke Yu, Hongxia Ma, Guangfu Jin, Jianhang Gong, Chongqi Sun, Xueying Zhao, Zhihua Yin, Lei Yang, Zhiqiang Li, Qifei Deng, Jiucun Wang, Wei Wu, Hong Zheng, Guoquan Zhou, Hongyan Chen, Peng Guan, Zhihang Peng, Yijiang Chen, Yongqian Shu, Lin Xu, Xiangyang Liu, Li Liu, Pin Xu, Baohui Han, Chunxue Bai, Yuxia Zhao, Haibo Zhang, Ying Yan, Christopher I Amos, Feng Chen, Wen Tan, Li Jin, Tangchun Wu, Dongxin Lin, Hongbing Shen
Journal: Nature Genetics (2012)
Susceptibility to glaucoma: differential comparison of the astrocyte transcriptome from glaucomatous African American and Caucasian American donors
Authors: Thomas J Lukas, Haixi Miao, Lin Chen, Sean M Riordan, Wenjun Li, Andrea M Crabb, Alexandria Wise, Pan Du, Simon M Lin, M ROSARIO Hernandez
Journal: Genome biology (2008)

Epidemiological and genetic studies indicate that ethnic/genetic background plays an important role in susceptibility to primary open angle glaucoma (POAG). POAG is more prevalent among the African-descent population compared to the Caucasian population. Damage in POAG occurs at the level of the optic nerve head (ONH) and is mediated by astrocytes. Here we investigated differences in gene expression in primary cultures of ONH astrocytes obtained from age-matched normal and glaucomatous donors of Caucasian American (CA) and African American (AA) populations using oligonucleotide microarrays. Gene expression data were obtained from cultured astrocytes representing 12 normal CA and 12 normal AA eyes, 6 AA eyes with POAG and 8 CA eyes with POAG. Data were normalized and significant differential gene expression levels detected by using empirical Bayesian shrinkage moderated t-statistics. Gene Ontology analysis and networks of interacting proteins were constructed using the BioGRID database. Network maps included regulation of myosin, actin, and protein trafficking. Real-time RT-PCR, western blots, ELISA, and functional assays validated genes in the networks. Cultured AA and CA glaucomatous astrocytes retain differential expression of genes that promote cell motility and migration, regulate cell adhesion, and are associated with structural tissue changes that collectively contribute to neural degeneration. Key upregulated genes include those encoding myosin light chain kinase (MYLK), transforming growth factor-β receptor 2 (TGFBR2), rho-family GTPase-2 (RAC2), and versican (VCAN). These genes along with other differentially expressed components of integrated networks may reflect functional susceptibility to chronic elevated intraocular pressure that is enhanced in the optic nerve head of African Americans.
Metabolic remodelling of the failing heart: the cardiac burn-out syndrome?
Authors: M VANBILSEN, P SMEETS, A GILDE, G VANDERVUSSE
Journal: Cardiovascular Research (2003)

It has been postulated that the failing heart suffers from chronic energy starvation, and that derangements in cardiac energy conversion are accessory to the progressive nature of this disease. The molecular mechanisms driving this ‘metabolic remodelling’ process and their significance for the development of cardiac failure are still open to discussion. Next to changes in mitochondrial function, the hypertrophied heart is characterized by a marked shift in substrate preference away from fatty acids towards glucose. It has been argued that the decline in fatty acid oxidation is not fully compensated for by a rise in glucose oxidation, thereby imposing an additional burden on overall ATP generating capacity. Several lines of evidence suggest that these metabolic adaptations are brought about, at least in part, by alterations in the rate of transcription of genes encoding for proteins involved in substrate transport and metabolism. Here, the principal metabolic changes are reviewed and the various molecular mechanisms that are likely to play a role are discussed. In addition, the potential significance of these changes for the aetiology of heart failure is evaluated.
Regulation of Vascular Calcification
Authors: Cecilia M. Giachelli, Mei Y. Speer, Xianwu Li, Rupak M. Rajachar, Hsueh Yang
Journal: Circulation Research (2005)

Vascular calcification is prevalent in aging as well as a number of pathological conditions, and it is now recognized as a strong predictor of cardiovascular events in the general population as well as diabetic and end-stage renal disease patients. Vascular calcification is a highly regulated process involving inductive and inhibitory mechanisms. This article focuses on two molecules, phosphate and osteopontin, that have been implicated in the induction or inhibition of vascular calcification, respectively. Elevated phosphate is of interest because hyperphosphatemia is recognized as a major nonconventional risk factor for cardiovascular disease mortality in end-stage renal disease patients. Studies to date suggest that elevated phosphate stimulates smooth muscle cell phenotypic transition and mineralization via the activity of a sodium-dependent phosphate cotransporter. Osteopontin, however, appears to block vascular calcification most likely by preventing calcium phosphate crystal growth and inducing cellular mineral resorption.
Précis of <i>Foundations of Language: Brain, Meaning, Grammar, Evolution,</i>
Authors: Ray Jackendoff
Journal: Behavioral and Brain Sciences (2003)

The goal of this study is to reintegrate the theory of generative grammar into the cognitive sciences. Generative grammar was right to focus on the child's acquisition of language as its central problem, leading to the hypothesis of an innate Universal Grammar. However, generative grammar was mistaken in assuming that the syntactic component is the sole course of combinatoriality, and that everything else is “interpretive.” The proper approach is a parallel architecture, in which phonology, syntax, and semantics are autonomous generative systems linked by interface components. The parallel architecture leads to an integration within linguistics, and to a far better integration with the rest of cognitive neuroscience. It fits naturally into the larger architecture of the mind/brain and permits a properly mentalistic theory of semantics. It results in a view of linguistic performance in which the rules of grammar are directly involved in processing. Finally, it leads to a natural account of the incremental evolution of the language capacity.
Epidermal hyperproliferation following the induction of microabscesses by leukotriene B4
Authors: F.W. BAUER, P.C.M. KERKHOF, R.M.MAASSEN-DE GROOD
Journal: British Journal of Dermatology (1986)

The percentage of non-diploid epidermal cells was determined by flow cytometry following application of leukotriene B4 (LTB4) to human skin. Doses in the range 35-500 ng were shown to cause a marked increase in proliferation, the non-diploid cells reaching a maximum between 72 and 96 h after LTB4 application. No difference was observed between the response of healthy controls and the uninvolved skin of psoriatic patients. We suggest, therefore, that the hyperproliferation is a consequence of the physical disruption of the stratum corneum accompanying the rupture of microabscesses.
Epidermal Growth Factor Receptor, Protein Kinase B/Akt, and Glioma Response to Erlotinib
Authors: Daphne A. Haas-Kogan, Michael D. Prados, Tarik Tihan, David A. Eberhard, Nannette Jelluma, Nils D. Arvold, Rachel Baumber, Kathleen R. Lamborn, Ami Kapadia, Mary Malec, Mitchel S. Berger, David Stokoe
Journal: JNCI Journal of the National Cancer Institute (2005)

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib (also known as Tarceva or OSI-774) has shown promising response rates in malignant gliomas. We investigated the association between expression of EGFR and downstream signaling components and the response of malignant gliomas to erlotinib in a phase I trial of erlotinib administered either alone or with the alkylating agent temozolomide.Expression of EGFR and ligand-independent EGFRvIII mutant proteins and of phosphorylated protein kinase B (PKB)/Akt in specimens from glioma patients were assessed by immunohistochemistry. EGFR gene amplification was evaluated by fluorescence in situ hybridization. Mutations in PTEN and EGFR were assessed by polymerase chain reaction amplification and sequencing. Response was evaluated by sequential magnetic resonance imaging every 2 months. The Cochran-Mantel-Haenzel test was used to assess associations between biomarker status and response. All statistical tests were two-sided.Of 41 glioma patients, eight responded to treatment. Response to erlotinib was associated with EGFR expression (P = .07) and EGFR amplification (P = .08). These associations were stronger and statistically significant among the 29 patients initially diagnosed with glioblastoma multiforme (P = .03 and P = .02, respectively). Among six responders with sufficient tumor tissue, none had EGFRvIII mutations. None of the 22 tumors with high levels of phosphorylated PKB/Akt responded to erlotinib treatment, whereas eight of the 18 tumors with low levels of phosphorylated PKB/Akt responded to erlotinib treatment (P < .001). The level of phosphorylated PKB/Akt was also associated with time to progression (P < .001).Among glioma patients, those with glioblastoma multiforme tumors who have high levels of EGFR expression and low levels of phosphorylated PKB/Akt had better response to erlotinib treatment than those with low levels of EGFR expression and high levels of phosphorylated PKB/Akt.
A high-resolution recombination map of the human genome
Authors: Augustine Kong, Daniel F. Gudbjartsson, Jesus Sainz, Gudrun M. Jonsdottir, Sigurjon A. Gudjonsson, Bjorgvin Richardsson, Sigrun Sigurdardottir, John Barnard, Bjorn Hallbeck, Gisli Masson, Adam Shlien, Stefan T. Palsson, Michael L. Frigge, Thorgeir E. Thorgeirsson, Jeffrey R. Gulcher, Kari Stefansson
Journal: Nature Genetics (2002)
Characterization of the rat connexin40 promoter: two Sp1/Sp3 binding sites contribute to transcriptional activation
Authors: M Bierhuizen
Journal: Cardiovascular Research (2000)

Objectives: The gap junction protein connexin40 (Cx40) is differentially expressed during embryonic development and in adult tissues, for which the molecular basis is unknown. In order to elucidate the molecular mechanisms controlling Cx40 expression, we set out to map and characterize its promoter. Methods: The transcriptional activity of individual rat Cx40 (rCx40)-derived promoter fragments fused to the luciferase reporter gene was determined by transfection/reporter assays in Cx40-expressing (A7r5, rat smooth muscle embryonic thoracic aorta cells, and BWEM, v-myc transformed rat fetal cardiomyocytes) and Cx40-nonexpressing cells (N2A, mouse neuroblastoma cells). The nature of DNA–protein interactions was investigated by a combination of standard electrophoretic-mobility-shift assays (EMSA) and EMSA/antibody supershift assays. Results: Quantification of luciferase activity in cell lysates revealed that a 235-base-pair fragment, in between map positions −150 and +85 relative to the transcription initiation site, is able to provide for a significant level of transcription in both Cx40-expressing (A7r5, BWEM) and -nonexpressing (N2A) cells. These results indicate that this region contains the basal promoter but is not sufficient to completely determine the endogenous Cx40-expression pattern within these cell types. In search for the responsible transcriptional regulatory element(s), additional segments of the (−150, +85) region were deleted and the remaining fragments were tested for transcriptional activity. These studies established that the regions in between map positions (−96, −71) and (+58, +85) contribute to promoter activity. EMSA with these regions revealed that predominantly two DNA–protein complexes are formed upon incubation with either A7r5, BWEM or N2A nuclear extracts, which could be both inhibited by including excess oligonucleotide containing the Sp1 consensus binding site in the binding reaction. Purified recombinant human Sp1 provided also for a shift in the EMSA using these promoter regions as target fragments. When the DNA–protein complexes formed with nuclear extract were subsequently incubated with either an anti-Sp1 or an anti-Sp3 antibody clear supershifts in the EMSA were obtained, indicating Sp1 and Sp3 binding to both the (−98, −64) and (+53, +87) regions. The introduction of mutations within the core sequence of the putative Sp1/Sp3 binding sites present in these regulatory elements reduced the level of transcriptional activity and abrogated Sp1/Sp3 binding to these sites. Conclusion: The results indicate that at least two Sp1/Sp3 binding sites in the rCx40 promoter contribute to the transcriptional activation of its gene in cultured cells.
Evidence on the effects of exercise therapy in the treatment of chronic disease
Authors: U M Kujala
Journal: British Journal of Sports Medicine (2009)

Evidence on the effects of exercise in the treatment of patients with chronic diseases should be based on well designed randomised controlled trials. The most consistent finding of the meta-analyses summarised in the present work is that aerobic/functional capacity and muscle strength can be improved by exercise training among patients with different diseases without having detrimental effects on disease progression. This is important, as with population aging exercise therapy may be an important means of reducing disability and increasing the number of older people living independently. Additionally, there is accumulating evidence that in patients with chronic disease exercise therapy is effective in improving the prognostic risk factor profile and, in certain diseases, in delaying mortality. In some diseases, such as osteoarthritis, pain symptoms may also be reduced. Severe complications during the exercise therapy programs were rare.
Sp1 Transcription Factor as a Molecular Target for Nitric Oxide– and Cyclic Nucleotide–Mediated Suppression of cGMP-Dependent Protein Kinase-Iα Expression in Vascular Smooth Muscle Cells
Authors: Hassan Sellak, Xiangli Yang, Xu Cao, Trudy Cornwell, Gerald A. Soff, Thomas Lincoln
Journal: Circulation Research (2002)

cGMP-dependent protein kinase (PKG) expression is highly variable and decreases in cultured vascular smooth muscle cells (VSMCs), exposure of cells to nitric oxide (NO), or in response to balloon catheter injury in vivo. In this study, the mechanisms of human type I PKG-alpha (PKG-Ialpha) gene expression were examined. Three structurally unrelated NO donors decreased PKG-Ialpha promoter activity after transfection of a promoter/luciferase construct in VSMCs. Promoter deletion analysis demonstrated that (1) a 120-bp promoter containing tandem Sp1 sites was sufficient to drive basal PKG-Ialpha promoter activity, and (2) NO was inhibitory at this site. Cyclic nucleotide analogues also suppressed PKG-Ialpha promoter activity with cAMP being more potent than cGMP. The effects of cyclic nucleotides to suppress PKG-Ialpha promoter activity were attenuated by a specific cAMP-dependent protein kinase (PKA) inhibitor. Single or double mutation of Sp1 binding sites abolished PKG-Ialpha expression. Moreover, Sp1 binding activity on the PKG-Ialpha promoter was detected in A7r5 cells, and this binding was inhibited by NO and cyclic nucleotides. These results indicate that PKG-Ialpha gene expression is driven by an Sp1 transcription mechanism, and that NO and cAMP inhibit Sp1-mediated PKG-Ialpha gene expression through separate mechanisms.