tbuckley/cabot-search huggingface dataset:
PTEN suppresses SPARC-induced pMAPKAPK2 and inhibits SPARC-induced Ser78 HSP27 phosphorylation in glioma
Authors: Ridwan Alam, Chad R. Schultz, William A. Golembieski, Laila M. Poisson, Sandra A. Rempel
Journal: Neuro-Oncology (2013)

Secreted protein acidic and rich in cysteine (SPARC) is overexpressed in astrocytomas (World Health Organization grades II–IV). We previously demonstrated that SPARC promotes glioma migration and invasion—in part, by activating the P38 mitogen-activated protein kinase (MAPK)–heat shock protein (HSP)27 signaling pathway. The commonly lost tumor suppressor phosphatase and tensin homolog (PTEN) suppresses SPARC-induced migration, which is accompanied by suppression of Shc-Ras-Raf-MEK-ERK1/2 and Akt signaling. As PTEN completely suppresses SPARC-induced migration, we proposed that PTEN must also interfere with SPARC-induced HSP27 signaling. Therefore, this study determined the effects of PTEN expression on SPARC-induced expression and phosphorylation of HSP27. Control and SPARC-expressing clones transfected with control- or PTEN-expression plasmids were plated on fibronectin-coated tissue culture plates for 3, 6, 24, and 48 h and then lysed. Equal amounts of protein were subjected to Western blot and densitometric analyses. The results show that SPARC enhances phosphorylated (p)P38 MAPK, phosphorylated MAPK-activated protein kinase 2 (pMAPKAPK2), and serine (Ser)78 HSP27 phosphorylation relative to total HSP27. PTEN suppresses pAkt and pMAPKAPK2, suggesting that PTEN effects are downstream of pP38 MAPK. PTEN suppressed SPARC-induced sustained phosphorylation at Ser78 HSP27. As the level of total HSP27 differed based on the presence of SPARC or PTEN, the ratios of phosphorylation-specific to total HSP27 were examined. The data demonstrate that SPARC-induced phosphorylation at Ser78 remains elevated despite increasing levels of total HSP27. In contrast, PTEN inhibits SPARC-induced increases in Ser78 HSP27 phosphorylation relative to total HSP27. These data describe a novel mechanism whereby PTEN inhibits SPARC-induced migration through suppression and differential regulation of pAkt and the P38 MAPK-MAPKAPK2-HSP27 signaling pathway.
Water Reclamation and Unrestricted Nonpotable Reuse: A New Tool in Urban Water Management
Authors: Daniel A. Okun
Journal: Annual Review of Public Health (2000)

▪ Abstract Growing urbanization accompanying growing population is increasing the demand for water supply in communities throughout the world. Water resources for many cities are already proving inadequate. Additional water resources are inherently more costly and are often not available because other communities and/or land owners have the water rights. Although conservation, particularly through demand management, may delay the need for additional sources for a short period, the need is inevitable. One approach that has been found to provide substantial additional water for communities is the reclamation of wastewaters produced by the communities themselves for unrestricted nonpotable purposes, such as for landscape and market crop irrigation, industry, cooling towers, air conditioning, toilet flushing, construction, vehicle washing, and environmental enhancement. This is done by providing dual distribution systems. Nonpotable reuse is already widely practiced despite the fact that the reclaimed water distribution systems needed to be installed in existing communities. Inasmuch as additional water is needed for growing populations, the costs would be substantially reduced if the two systems were to be built at the same time in the newly developing areas. Reuse of reclaimed water for potable purposes may be feasible, but it imposes added public health risks that need to be accepted only as a last resort.
Evidence for Virus-Related and Unrelated Antigens on Murine Lymphomas Induced by Chemical Carcinogens
Authors: Maria I. Colnaghi, Giuseppe Della Porta
Journal: JNCI Journal of the National Cancer Institute (1973)

Ether-treated extracts of 7 CS7BL lymphosarcomas induced by 3 different chemical carcinogens, urethan (Ur), N-nitrosomethylurea (NMU) or 7,12-dimethylbenz[a]anthracene (DMBA), were tested by immunodiffusion for the presence of group-specific antigens and all were found positive. Direct cytotoxic tests and absorption tests with a murine anti-G serum and a rat antiradiation leukemia virus (RadLV) serum, using 9 other Ur, NMU, or DMBA-induced CS7BL lymphomas, demonstrated the presence of common cell-surface, virus-related antigens on the virus-induced E♂G2 leukemia, the RadLV lymphoma, and the chemically induced lymphomas. An antiserum raised in CS7BL against Ur-induced C3Hf or BALB/c lymphomas exhibited a complement-dependent cytotoxic activity against 21 of 22 CS7BL lymphomas induced by the 3 different carcinogens, against the EL4 leukemia but not against the virus-induced E♂G2 leukemia. The E♂G2 leukemia also failed to absorb completely the specific cytotoxicity of the entlehemlcally induced lyrmphomas antiserum. CS7BL multiparous or antiembryo sera exerted a complement-dependent cytotoxicity on the chemically induced lymphomas but not on the E♂G2 leukemia. Thus carcinogeninduced lymphosarcomas, in addition to Gross virus-related antigens, possess tumor-specific, cell-surface, cross-reacting antigens not related to the virus, which may represent modified expressions of cellular genetic information and/or a retrogenetic expression.
Is there a need for new thresholds to define remission and low disease activity by Disease Activity Score 28 calculated with C reactive protein? Real life data from a local registry
Authors: Ennio Giulio Favalli, Andrea Becciolini, Martina Biggioggero, Antonio Marchesoni, Pier Luigi Meroni
Journal: Annals of the Rheumatic Diseases (2014)

Is there a need for new thresholds to define remission and low disease activity by Disease Activity Score 28 calculated with C reactive protein?Real life data from a local registryWe read with great interest the recent article by Fleischmann et al which reports a post hoc analysis of five rheumatoid arthritis (RA) randomised clinical trials (RCTs) to evaluate the correlation between Disease Activity Score in 28 joints calculated by using erythrocyte sedimentation rate (DAS28-ESR) or C reactive protein (DAS28-CRP). 1Since its introduction, 2 DAS28-CRP has been used to evaluate clinical response in RCTs and daily practice by applying the same DAS28-ESR thresholds to define remission and low disease activity (LDA).Consistently with some previous reports, 3-5 Fleischmann et al demonstrated that DAS28-CRP underestimates disease activity when using the same remission and LDA cut-off points validated for DAS28-ESR (2.6 and 3.2, respectively). 6Based on these findings, the authors suggested new thresholds for DAS28-CRP (2.4 for remission and 2.9 for LDA) that significantly decrease the proportion of discordance between the two composite indices in defining remission and LDA.Still several recent RCTs employ DAS28-CRP applying the DAS28-ESR cut-off points as a primary outcome measure, and many rheumatologists use DAS28-CRP over DAS28-ESR to assess RA disease activity and implement treat-to-target strategy in daily practice.Hence, we felt it would be very useful to validate the newly introduced DAS28-CRP thresholds in a real life setting.In order to test the performance of standard versus new DAS28-CRP cut-offs, we extracted from a local registry data on all patients with RA treated with biological agents in our rheumatology unit between October 1999 and August 2013.The selected study population consisted of 562 patients receiving a total of 887 lines of biologic therapy (71 abatacept, 197 adalimumab, 15 anakinra, 45 certolizumab pegol, 230 etanercept, 18 golimumab, 237 infliximab and 74 rituximab) with a minimum follow-up period of 12 months.For each line of therapy DAS28-ESR and DAS28-CRP (using the old and the newly proposed thresholds) response rates were calculated at 6-month and 12-month checkpoints, carrying the last observation forward for patients who were missing the selected study end points.As reported in table 1, the percentage of patients achieving remission or LDA at both the checkpoints was lower for DAS28-ESR than DAS28-CRP when using standard cut-offs for both measures.As a consequence, the proportion of discordance
FREQUENCY, CLINICAL AND ANGIOGRAPHIC CHARACTERISTICS, AND OUTCOMES OF HIGH-RISK NON-ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROMES PATIENTS WITH LEFT CIRCUMFLEX CULPRIT LESIONS
Authors: Uwe Zeymer, Robert Clare, Marc Schweiger, Arnoud van&apos;t Hof, Judith Hochman, Stefan James, Harvey White, Petr Widimsky, Amadeo Betriu, Christoph Bode, Robert Califf, Robert Harrington, Robert Giugliano, C. Michael Gibson, L. Kristin Newby
Journal: Journal of the American College of Cardiology (2012)
Metabolic alterations in human synovial lining cells in pigmented villonodular synovitis.
Authors: B Henderson, L Bitensky, J J Johnstone, A Catterall, J Chayen
Journal: Annals of the Rheumatic Diseases (1979)

Synovial tissue from 3 patients with villonodular synovitis has been examined by quantitative cytochemistry. Considerable changes in the metabolism of the synoviocytes have been observed. These included a massive rise in the activity of glucose 6-phosphate dehydrogenase to levels even greater than those found in rheumatoid arthritis, and a significant rise in the activity of 2 glycolytic enzymes, glyceraldehyde 3-phosphate and lactate dehydrogenase. Lysosomal napthhylamidase showed raised activity with no latency. The sulphydryl content in the synoviocytes was raised, as was the amount of available phospholipid. This pattern of metabolic alterations is similar to that found in human rheumatoid synoviocytes.
The Elusive Goal of Maintaining Population Cancer Screening: It Is Time for a New Paradigm
Authors: Jeanne Mandelblatt, Diana Buist
Journal: JNCI Journal of the National Cancer Institute (2010)

Screening mammography is credited, in part, for the success in reducing the mortality from breast cancer in the United States (1). However, screening uptake has not been universal nor has it been adopted for regular use by all eligible women. In this issue of the Journal, Vernon et al. conducted a methodologically rigorous review of the literature on controlled behavioral interventions to increase repeat mammography screening among women at average risk for the disease (2). Their results are sobering: Behavioral interventions only increase rates by a small to moderate amount, and there is insufficient evidence to know which approaches are the most effective (2). These results are all the more discouraging because the reviewed studies focused on getting women to undergo only one to two repeat screening examinations and not the 12–13 biennial screenings presently recommended for average risk women aged 50–74 years (3). Even intensive counseling approaches, which included patient navigation (patient education and assistance), showed only a modest return for their high resource intensity. The most effective approaches reported by studies in this analysis appear to be reminder systems, but those studies were too heterogeneous to provide definitive evidence
Effect of tumour necrosis factor blockers on radiographic progression of psoriatic arthritis: a systematic review and meta-analysis of randomised controlled trials
Authors: Radjiv Goulabchand, Gaël Mouterde, Thomas Barnetche, Cédric Lukas, Jacques Morel, Bernard Combe
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) of psoriatic arthritis (PsA) to examine the effect of tumour necrosis factor (TNF) blockers on radiographic progression, and to determine whether treatment combining TNF blocker with methotrexate (MTX) was superior to TNF-blocker monotherapy. <h3>Methods</h3> We systematically reviewed articles published up to December 2012 in Embase and Medline, and from the two last EUropean League Against Rheumatism (EULAR) and American College or Rheumatology (ACR) meetings. The primary endpoint was the proportion of patients with no radiographic progression (non-progressors) at treatment week 24 (defined by change in modified total Sharp score (mTSS) ≤0.5). The Mantel–Haenszel method was used to estimate ORs and 95% CIs of the effect of TNF blockers (with or without MTX) versus placebo (with or without MTX). Statistical heterogeneity was assessed by χ² test. <h3>Results</h3> The search retrieved 207 articles; 5 (1110 patients) met the meta-analysis criteria. For patients receiving TNF blockers, 494/584 (84.5%) were considered non-progressors at treatment week 24 vs 362/526 (68.8%) receiving placebo (OR 2.68 (95% CI 1.99 to 3.60) p&lt;0.001), without significant heterogeneity (I<sup>2</sup>=3%; p=0.39). Only three RCTs provided data on potential additional efficacy of MTX: two did not find significant difference, one suggested a benefit of combined therapy. <h3>Conclusions</h3> For patients with PsA, control of structural damage is better at week 24 with TNF blockers than placebo. Due to the limited data, we were unable to conclude on the potential additional effect of MTX on structural damages.
Of mice and men: the iron age
Authors: S. Vaulont
Journal: Journal of Clinical Investigation (2005)

Recently, mutations causing juvenile hemochromatosis have been identified in a novel gene, hemojuvelin (HJV), located on chromosome 1. Mouse models of this disease have now been developed by 2 groups, Huang et al. and Niederkofler et al., through targeted disruption of the Hjv gene (see the related articles beginning on pages 2180 and 2187). These mutant mice will allow further investigation into the role of HJV in the regulation of iron homeostasis, a role that to date remains elusive.
Prevalence of Allergic Disease in Foreign-Born American Children
Authors: Jonathan I. Silverberg, Eric L. Simpson, Helen G. Durkin, Rauno Joks
Journal: JAMA Pediatrics (2013)

<h3>Importance</h3>Improved understanding of allergic disease epidemiology lead to novel therapeutic and prevention strategies.<h3>Objectives</h3>To study the association between US birthplace and prevalence of childhood allergic disease and to determine the effects of prolonged US residence on allergic disease.<h3>Design, Setting, Participants</h3>Cross-sectional questionnaire distributed to 91 642 children aged 0 to 17 years enrolled in the 2007-2008 National Survey of Children's Health.<h3>Exposure</h3>Place of birth.<h3>Main Outcome and Measure</h3>Prevalence of allergic disease, including asthma, eczema, hay fever, and food allergies.<h3>Results</h3>Children born outside the United States had significantly lower odds of any atopic disorders than those born in the United States (logistic regression OR, 0.48; 95% CI, 0.38-0.61), including ever-asthma (0.53; 0.39-0.72), current-asthma (0.34; 0.23-0.51), eczema (0.43; 0.30-0.61), hay fever (0.39; 0.27-0.55), and food allergies (0.60; 0.37-0.99). The associations between child's birthplace and atopic disorders remained significant in multivariate models including age, sex, race/ethnicity, annual household income, residence in metropolitan areas, and history of child moving to a new address. Children born outside the United States whose parents were also born outside the United States had significantly lower odds of any atopic disorders than those whose parents were born in the United States (P = .005). Children born outside the United States who lived in the United States for longer than 10 years when compared with those who resided for only 0 to 2 years had significantly higher odds of developing any allergic disorders (adjusted OR, 3.04; 95% CI, 1.08-8.60), including eczema (4.93; 1.18-20.62; P = .03) and hay fever (6.25; 1.70-22.96) but not asthma or food allergies (P ≥ .06).<h3>Conclusions and Relevance</h3>Children born outside the United States have a lower prevalence allergic disease that increases after residing in the United States for 1 decade.
A comparison of small bowel MRI with small bowel follow through and ileo-colonoscopy in patients with small bowel crohn's disease in a non-university setting
Authors: R. K. Felwick, J. Elford, G. Matthews, J. N. Gordon
Journal: Gut (2011)

<h3>Introduction</h3> In the UK small bowel follow-through (SBFT) is the current standard for investigating small bowel Crohn9s disease. However advances in small bowel MRI (SB-MRI) mean that it is now a viable alternative with the advantage of no ionizing radiation and the potential ability to differentiate active from inactive disease and identify extra-intestinal pathology. We therefore wished to analyse the clinical utility of SB-MRI in the investigation of small bowel Crohn9s disease, and correlate the findings with SBFT, ileo-colonoscopy and inflammatory markers. <h3>Methods</h3> Data was prospectively collected on 100 sequential patients with small bowel Crohn9s disease who underwent SB-MRI over the last year. 48 patients also underwent parallel SBFT, 53 parallel ileo-colonoscopy and 80 patients had inflammatory markers measured. Results from the 3 groups were compared. <h3>Results</h3> SB-MRI and SBFT were equally effective in identifying the presence or absence of small bowel Crohn9s disease. However SB-MRI was more accurate in the identification of strictures and allowed more precise localisation. In addition MRI was able to differentiate active from inactive disease, identify extra-intestinal pathology and provide information on colonic involvement. SB-MRI estimation of disease activity correlated well with both endoscopic and histological findings, with 93% of patients correctly identified as having either active or quiescent disease. Inflammatory markers correlated poorly with MRI, endoscopic and histological findings with 46% of patients with active disease by any modality having a normal CRP or ESR. <h3>Conclusion</h3> SB- MRI is superior to SBFT in the investigation of small bowel Crohn9s disease as in addition to identifying structural disease it provides information on stricture location, disease activity, colonic involvement and extra-intestinal pathology without exposing patients to ionising radiation. We believe that SB-MRI should now replace SBFT as the investigation of choice for small bowel Crohn9s disease.
Characterization of thimet oligopeptidase and neurolysin activities in B16F10-Nex2 tumor cells and their involvement in angiogenesis and tumor growth
Authors: Thaysa Paschoalin, Adriana K Carmona, Elaine G Rodrigues, Vitor Oliveira, Hugo P Monteiro, Maria A Juliano, Luiz Juliano, Luiz R Travassos
Journal: Molecular Cancer (2007)

Abstract Background Angiogenesis is a fundamental process that allows tumor growth by providing nutrients and oxygen to the tumor cells. Beyond the oxygen diffusion limit from a capillary blood vessel, tumor cells become apoptotic. Angiogenesis results from a balance of pro- and anti-angiogenic stimuli. Endogenous inhibitors regulate enzyme activities that promote angiogenesis. Tumor cells may express pro-angiogenic factors and hydrolytic enzymes but also kinin-degrading oligopeptidases which have been investigated. Results Angiogenesis induced by B16F10-Nex2 melanoma cells was studied in a co-culture with HUVEC on Matrigel. A stimulating effect on angiogenesis was observed in the presence of B16F10-Nex2 lysate and plasma membrane. In contrast, the B16F10-Nex2 culture supernatant inhibited angiogenesis in a dose-dependent manner. This effect was abolished by the endo-oligopeptidase inhibitor, JA-2. Thimet oligopeptidase (TOP) and neurolysin activities were then investigated in B16F10-Nex2 melanoma cells aiming at gene sequencing, enzyme distribution and activity, influence on tumor development, substrate specificity, hydrolytic products and susceptibility to inhibitors. Fluorescence resonance energy transfer (FRET) peptides as well as neurotensin and bradykinin were used as substrates. The hydrolytic activities in B16F10-Nex2 culture supernatant were totally inhibited by o -phenanthrolin, JA-2 and partially by Pro-Ile. Leupeptin, PMSF, E-64, Z-Pro-Prolinal and captopril failed to inhibit these hydrolytic activities. Genes encoding M3A enzymes in melanoma cells were cloned and sequenced being highly similar to mouse genes. A decreased proliferation of B16F10-Nex2 cells was observed in vitro with specific inhibitors of these oligopeptidases. Active rTOP but not the inactive protein inhibited melanoma cell development in vivo increasing significantly the survival of mice challenged with the tumor cells. On Matrigel, rTOP inhibited the bradykinin – induced angiogenesis. A possible regulation of the homologous tumor enzyme in the perivascular microenvironment is suggested based on the observed rTOP inhibition by an S-nitrosothiol NO donor. Conclusion Data show that melanoma cells secrete endo-oligopeptidases which have an important role in tumor proliferation in vitro and in vivo. rTOP inhibited growth of subcutaneously injected B16F10-Nex2 cells in mice. TOP from tumor cells and bradykinin in endothelial cells are two antagonist factors that may control angiogenesis essential for melanoma growth. A regulatory role of NO or S-nitrosothiols is suggested.
Torture: The Guantanamo Guidebook; Is Torture a Good Idea?
Authors: Trevor Jackson
Journal: BMJ (2005)

Torture: The Guantanamo Guidebook . Channel 4, 28 February at 11 05 pm Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Is Torture a Good Idea? . Channel 4, 28 February at 8 pm Rating: ![Graphic][5]</img>![Graphic][6]</img>![Graphic][7]</img>![Graphic][8]</img> E ver wondered what it's like to be detained in Guantanamo Bay? Seven British volunteers, including several Muslims, were given the chance to find out, courtesy of Channel 4, as part of a week-long series of programmes on torture. Reporting to a specially equipped ware-house, they were ambushed, hooded, kidnapped, shackled, caged, and subjected to a range of Pentagon approved interrogation techniques that included sensory deprivation, “sleep adjustment,” religious and sexual humiliation, and severe physical pain. But Torture: The Guantanamo Guidebook was no Big Brother -style reality show. This was a serious attempt to examine the effects of torture on the body and the psyche, and to bring home to viewers the kind of interrogation techniques that are being employed in the US-led so called “war on terror.” “Tonight we recreate 48 hours in Guantanamo Bay,” announced presenter Jon Snow, better known as the face of Channel 4 News . “All the interrogation methods you see have been officially … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif [5]: /embed/inline-graphic-5.gif [6]: /embed/inline-graphic-6.gif [7]: /embed/inline-graphic-7.gif [8]: /embed/inline-graphic-8.gif
Phase II study of pegylated liposomal doxorubicin (Caelyx®) and docetaxel as first-line treatment in metastatic breast cancer
Authors: A. Alexopoulos, M.V. Karamouzis, H. Stavrinides, A. Ardavanis, K. Kandilis, J. Stavrakakis, C. Georganta, G. Rigatos
Journal: Annals of Oncology (2004)