tbuckley/cabot-search huggingface dataset:
The Serine Protease Inhibitor Protease Nexin-1 Controls Mammary Cancer Metastasis through LRP-1–Mediated MMP-9 Expression
Authors: Bérengère Fayard, Fabrizio Bianchi, Julien Dey, Eliza Moreno, Sabrina Djaffer, Nancy E. Hynes, Denis Monard
Journal: Cancer Research (2009)

Abstract Through their ability to degrade the extracellular matrix, proteases mediate cancer cell invasion and metastasis. Paradoxically, some serine protease inhibitors (serpins) are often overexpressed in human tumors. Using computational analysis, we found that the RNA level of protease nexin-1 (PN-1), a serpin that blocks numerous proteases activity, is significantly elevated in estrogen receptor-α-negative and in high-grade breast cancer. The in silico approach was complemented by mechanistic studies on two mammary cancer cell lines, the PN-1-negative 168FARN cells and the PN-1-positive 4T1 cells, both of which form primary mammary tumors, but only 4T1 tumors are able to metastasize to the lungs. We show that treatment of 168FARN cells with PN-1 stimulates extracellular signal-regulated kinase activation via low-density lipoprotein receptor-related protein-1 (LRP-1) binding, resulting in increased matrix metalloproteinase (MMP)-9 RNA, protein, and secreted activity. PN-1–silenced 4T1 cells express low MMP-9 levels. Moreover, injection of PN-1–silenced cells into mice did not affect 4T1 primary mammary tumor outgrowth; however, the tumors had impaired metastatic potential, which could be restored by reexpressing soluble MMP-9 in the PN-1–silenced 4T1 cells. Thus, using mammary tumor models, we describe a novel pathway whereby the serpin PN-1 by binding LRP-1 stimulates extracellular signal-regulated kinase signaling, MMP-9 expression, and metastatic spread of mammary tumors. Importantly, an analysis of 126 breast cancer patients revealed that those whose breast tumors had elevated PN-1 levels had a significantly higher probability to develop lung metastasis, but not metastasis to other sites, on relapse. These results suggest that PN-1 might become a prognostic marker in breast cancer. [Cancer Res 2009;69(14):5690–8]
Central sleep apnoea in congestive heart failure despite vagal denervation after bilateral lung transplantation
Authors: P Solin, GI Snell, TJ Williams, MT Naughton
Journal: European Respiratory Journal (1998)

Nonhypercapnic central sleep apnoea is a disorder of respiratory control characterized by hyperventilation previously attributed to the stimulation of either pulmonary vagal afferent nerve fibres or respiratory chemoreceptors. This report describes central sleep apnoea in a patient with congestive heart failure following bilateral lung transplant in whom pulmonary vagal afferent nerve activity was absent.
Effects of Ramipril on Coronary Events in High-Risk Persons
Authors: Gilles R. Dagenais, Salim Yusuf, Martial G. Bourassa, Qilong Yi, Jackie Bosch, Eva M. Lonn, Simon Kouz, John Grover
Journal: Circulation (2001)

In trials of patients with left ventricular dysfunction or heart failure, ACE inhibitor use was unexpectedly associated with reduced myocardial infarction (MI). Using the Heart Outcomes Prevention Evaluation (HOPE) trial data, we tested prospectively whether ramipril, an ACE inhibitor, could reduce coronary events and revascularization procedures among patients with normal left ventricular function.In the HOPE trial, 9297 high-risk men and women, >/=55 years of age with previous cardiovascular disease or diabetes plus 1 risk factor, were randomly assigned to ramipril (up to 10 mg/d), vitamin E (400 IU/d), their combination, or matching placebos. During the mean follow-up of 4.5 years, there were 482 (10.4%) patients with clinical MI and unexpected cardiovascular death in the ramipril group compared with 604 (12.9%) in the placebo group [relative risk reduction (RRR), 21% (95% CI) (11,30); P<0.0003]. Ramipril was associated with a trend toward less fatal MI and unexpected death [4.0% versus 4.7%; RRR, 16% (-3, 31)] and with a significant reduction in nonfatal MI [5.6% versus 7.2%; RRR, 23% (9,34)]. Risk reductions in MI were documented in participants taking or not taking beta-blockers, lipid lowering, and/or antiplatelet agents. Although ramipril had no impact on hospitalizations for unstable angina [11.9% versus 12.2%; RRR, 3% (-9,14)], it reduced the risk of worsening and new angina [27.2% versus 30.0%; RRR, 12% (5,18); P<0.0014] and coronary revascularizations [12.5% versus 14.8%; RRR, 18%; (8,26) P<0.0005].In this high-risk cohort, ramipril reduced the risk of MI, worsening and new angina, and the occurrence of coronary revascularizations.
Should English healthcare providers be penalised for failing to collect patient-reported outcome measures? A retrospective analysis
Authors: Nils Gutacker, Andrew Street, Manuel Gomes, Chris Bojke
Journal: Journal of the Royal Society of Medicine (2015)

Summary Objective The best practice tariff for hip and knee replacement in the English National Health Service (NHS) rewards providers based on improvements in patient-reported outcome measures (PROMs) collected before and after surgery. Providers only receive a bonus if at least 50% of their patients complete the preoperative questionnaire. We determined how many providers failed to meet this threshold prior to the policy introduction and assessed longitudinal stability of participation rates. Design Retrospective observational study using data from Hospital Episode Statistics and the national PROM programme from April 2009 to March 2012. We calculated participation rates based on either (a) all PROM records or (b) only those that could be linked to inpatient records; constructed confidence intervals around rates to account for sampling variation; applied precision weighting to allow for volume; and applied risk adjustment. Setting NHS hospitals and private providers in England. Participants NHS patients undergoing elective unilateral hip and knee replacement surgery. Main outcome measures Number of providers with participation rates statistically significantly below 50%. Results Crude rates identified many providers that failed to achieve the 50% threshold but there were substantially fewer after adjusting for uncertainty and precision. While important, risk adjustment required restricting the analysis to linked data. Year-on-year correlation between provider participation rates was moderate. Conclusions Participation rates have improved over time and only a small number of providers now fall below the threshold, but administering preoperative questionnaires remains problematic in some providers. We recommend that participation rates are based on linked data and take into account sampling variation.
Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis
Authors: Masafumi Uno, Seiichiro Kurita, Hirofumi Misu, Hitoshi Ando, Tsuguhito Ota, Naoto Matsuzawa‐Nagata, Yuki Kita, Satoko Nabemoto, Hiroshi Akahori, Yoh Zen, Yasuni Nakanuma, Shuichi Kaneko, Toshinari Takamura
Journal: Hepatology (2008)

Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease and is one of the most common liver diseases in the developed world. The histological findings of NASH are characterized by hepatic steatosis, inflammation, and fibrosis. However, an optimal treatment for NASH has not been established. Tranilast, N-(3',4'-dimethoxycinnamoyl)-anthranilic acid, is an antifibrogenic agent that inhibits the action of transforming growth factor beta (TGF-beta). This drug is used clinically for fibrogenesis-associated skin disorders including hypertrophic scars and scleroderma. TGF-beta plays a central role in the development of hepatic fibrosis, and tranilast may thus ameliorate the pathogenesis of NASH. We investigated the effects of tranilast using an established dietary animal model of NASH, obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and nondiabetic control Long-Evans Tokushima Otsuka (LETO) rats fed a methionine-deficient and choline-deficient diet. Treatment with 2% tranilast (420 mg/kg/day) for 8 weeks prevented the development of hepatic fibrosis and the activation of stellate cells, and down-regulated the expression of genes for TGF-beta and TGF-beta-target molecules, including alpha1 procollagen and plasminogen activator-1. In addition, tranilast attenuated hepatic inflammation and Kupffer cell recruitment, and down-regulated the expression of tumor necrosis factor alpha. Unexpectedly, tranilast ameliorated hepatic steatosis and up-regulated the expression of genes involved in beta-oxidation, such as peroxisome proliferator-activated receptor alpha and carnitine O-palmitoyltransferase-1. Most of these effects were observed in LETO rats and OLETF rats, which suggest that the action of tranilast is mediated through the insulin resistance-independent pathway.Our findings suggest that targeting TGF-beta with tranilast represents a new mode of therapy for NASH.
Deposition and clinical efficacy of terbutaline sulphate from Turbuhaler, a new multi-dose powder inhaler
Authors: S P Newman, F Morén, E Trofast, N Talaee, S W Clarke
Journal: European Respiratory Journal (1989)

A radioaerosol technique has been developed in order to assess deposition patterns from a new metered dose powder inhaler (Turbuhaler, Astra Pharmaceuticals). The radionuclide Tc99m dissolved in chloroform was added to a spheronised formulation of micronised terbutaline sulphate and the chloroform was allowed to evaporate. Turbuhaler subsequently delivered 0.5 mg of treated drug per metered dose. In vitro tests with a multistage liquid impinger showed that the fractionation of the drug dose between different particle size bands was similar to the fractionation of radioactivity. In a group of ten asthmatic patients, a mean 14.2% (SEM 2.1) of the drug dose was deposited in the lungs, with 71.6% (3.0) of the dose in the oropharynx. Of the remainder, 13.7% (2.1) was deposited on the mouthpiece, and 0.5% (0.2) recovered from exhaled air. The radiolabel was present in both central and peripheral zones of the lungs. All patients bronchodilated; forced expiratory volume in one second (FEV1) increased from 1.40 (0.24) l to 1.77 (0.24) l (p less than 0.01) 20 min after inhalation. These results suggest that both the distribution of drug and the clinical effect of terbutaline sulphate delivered from Turbuhaler are similar to those from a pressurised metered dose inhaler (MDI).
Effects of Periodic Mental Stress on Serum Cholesterol Levels
Authors: SCOTT M. GRUNDY, A. CLARK GRIFFIN
Journal: Circulation (1959)

The effects of academic final examinations on serum cholesterol levels were studied on 2 groups of medical students. A significant increase in the mean total serum cholesterol levels were observed during examination periods as compared to control periods of relaxation. These findings support previous reports of the effects of mental tension on serum cholesterol levels.
Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenström macroglobulinemia in first relapse or with primary refractory disease
Authors: Véronique Leblond, Vincent Lévy, Frédéric Maloisel, Bruno Cazin, Jean-Paul Fermand, Jean-Luc Harousseau, Liliane Remenieras, Raphaël Porcher, Martine Gardembas, Gérald Marit, Eric Deconinck, Bernard Desablens, François Guilhot, Guilaine Philippe, Aspasia Stamatoullas, Odile Guibon
Journal: Blood (2001)
Methods and Processes of the CONSORT Group: Example of an Extension for Trials Assessing Nonpharmacologic Treatments
Authors: Isabelle Boutron, David Moher, Douglas G. Altman, Kenneth F. Schulz, Philippe Ravaud
Journal: Annals of Internal Medicine (2008)

Background: The conduct of randomized, controlled trials of nonpharmacologic treatments presents specific challenges that are not adequately addressed in trial reports. Objective: To develop an extension of the CONSORT (Consolidated Standards of Reporting Trials) Statement for trials of nonpharmacologic treatments. Design: A consensus meeting was organized to develop an extension of the CONSORT Statement that addresses randomized trials of nonpharmacologic treatments. To prepare for the meeting, a survey was conducted to identify the specific issues for discussion. Setting: Consensus meeting in Paris, France. Participants: A total of 33 experts attended the meeting. The experts were methodologists (n = 17); surgeons (n = 6); editors (n = 5); and clinicians involved in rehabilitation (n = 1), psychotherapy (n = 2), education (n = 1), and implantable devices (n = 1). Measurements: Experts indicated which of the 22 items on the CONSORT checklist should be modified or which additional items should be added specifically for nonpharmacologic treatments. During a 3-day consensus meeting, all items were discussed and additional methodological issues related to nonpharmacologic research were identified. Results: The consensus was that 11 items on the CONSORT checklist needed some modifications for nonpharmacologic trials: item 1 (title and abstract), item 3 (participants), item 4 (interventions), item 7 (sample size), item 8 (randomization), item 11 (blinding), item 12 (statistical methods), item 13 (participant flow), item 15 (baseline data), item 20 (discussion: interpretation), and item 21 (generalizability). In addition, the meeting participants added 1 item related to implementation of the intervention. Limitation: Evidence was not always available to support the inclusion of each checklist item. Conclusion: The methods and processes used to develop this extension could be used for other reporting guidelines. The use of this extension to the CONSORT Statement should improve the quality of reporting randomized, controlled trials assessing nonpharmacologic treatments.
Clinical response to ustekinumab in familial pityriasis rubra pilaris caused by a novel mutation in<i>CARD14</i>
Authors: O. Eytan, O. Sarig, E. Sprecher, M.A.M. van Steensel
Journal: British Journal of Dermatology (2014)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Pityriasis rubra pilaris (PRP) manifests with erythematous scaly plaques, typically involving the scalp, trunk and limbs, associated with a yellowish diffuse palmoplantar keratoderma (PPK).1 Familial PRP is a very rare entity, which is inherited as an autosomal dominant trait.1 Recently, gain‐of‐function mutations in CARD14, which encodes the caspase recruitment domain family member 14, were identified as the cause of familial PRP and found to be associated with increased expression of CARD14 in the epidermis of affected patients.2 CARD14 is a known activator of the noncanonical nuclear factor‐kappa B (NF‐κB) pathway, leading to the activation of the inflammatory response.3 Herein, we describe the beneficial effect of ustekinumab in a case of familial PRP caused by a novel mutation in CARD14 that was refractory to multiple other therapeutic approaches. A 57‐year‐old man was referred for investigation of near‐erythroderma. The patient had experienced erythematous scaly plaques over most parts of the body since childhood. His father, a younger sister and his daughter were similarly affected (Fig. 1a). Physical examination revealed a diffuse and symmetric rash, involving the trunk and limbs, consisting of large scaly plaques and distinct islands of sparing. PPK and follicular accentuation were also noted (Fig. 1b,c). The patient was obese. Initially, psoriasis was diagnosed, but the clinical findings were, upon reconsideration during subsequent visits, deemed more consistent with PRP. Histopathology was not conclusive, showing epithelial hyperplasia with alternating para‐ and orthohyperkeratosis, and a mild lymphohistiocytic perivascular infiltrate (not shown).
Simultaneous prevention of unintended pregnancy and STIs: a challenging compromise
Authors: J.L.H. Evers, T. Farley, K. Gemzell-Danielsson, A. Glasier, P. Hannaford, C. La Vecchia, C. Moreau, J. Stephenson, D.T. Baird, P.G. Crosignani, L. Gianaroli, A. Glasier, P.G. Crosignani
Journal: Human Reproduction Update (2014)

BACKGROUNDUnintended pregnancy and sexually transmitted infections (STIs) are the major negative consequences of unsafe sex. Both are common and have long-term social and health consequences. Barrier methods of contraception can prevent both, but unfortunately they are much less effective than the more modern methods at pregnancy prevention. Modern effective contraceptives, however, do not protect against STIs and some may increase the risk of acquisition of infection. This comprehensive review discusses the magnitude of burden of reproductive ill-health, focussing on data from the European region, and explores the relationship between contraceptive use and STIs.
Chronic Pericarditis with Effusion
Authors: PAUL S. BARKER, FRANKLIN D. JOHNSTON
Journal: Circulation (1950)

Pericarditis with effusion is sometimes a chronic disease, an exception to the general rule that it is acute rather than chronic. Illustrative cases are described. Features of interest are the prominent third heart sound, the large P waves, the thrombi in the right atrium, the progression to constrictive pericarditis, and the resemblance in several respects to mitral stenosis.
Estimation of the risk for nutritional state degradation in patients with cancer: development of a screening tool based on results from a cross-sectional survey
Authors: A. Nourissat, D. Mille, G. Delaroche, J.P. Jacquin, J.M. Vergnon, P. Fournel, P. Seffert, J. Porcheron, P. Michaud, Y. Merrouche, F. Chauvin
Journal: Annals of Oncology (2007)
Exposure to Terrorism, Stress-Related Mental Health Symptoms, and Coping Behaviors Among a Nationally Representative Sample in Israel
Authors: Avraham Bleich
Journal: JAMA (2003)

The terrorist attacks on Israeli society have been ongoing since September 2000. However, few studies have examined the impact of terrorism on nationally representative population samples, and no study has examined the psychological impact of ongoing terrorism in Israel.To determine the level of exposure to terrorist attacks and the prevalence of traumatic stress-related (TSR) symptoms, symptoms of posttraumatic stress disorder (PTSD), and sense of safety after 19 months of terrorism in Israel, and to identify correlates of the psychological sequelae and the modes of coping with the terrorism.Telephone survey conducted April-May 2002, using a strata sampling method, of 902 eligible households and a representative sample of 742 Israeli residents older than 18 years (82% contact rate) and a final participation of 512 (57%).Number of TSR symptoms, rates of those with symptom criteria for PTSD and acute stress disorder assessed by the Stanford Acute Stress Reaction Questionnaire, self-reported feelings of depression, optimism, sense of safety, help-seeking, and modes of coping.Of 512 survey participants, 84 (16.4%) had been directly exposed to a terrorist attack and 191 (37.3%) had a family member or friend who had been exposed. Of 510 participants who responded to questions about TSR symptoms, 391 (76.7%) had at least 1 TSR symptom (mean, 4.0 [SD, 4.5]; range, 0-23; mean intensity, 0.8; range, 0-4). Symptom criteria for PTSD were met by 48 participants (9.4%) and criteria for acute stress disorder, by 1 participant; 299 (58.6%) reported feeling depressed. The majority of respondents expressed optimism about their personal future (421/512 [82.2%]) and the future of Israel (307/509 [66.8%]), and expressed self-efficacy with regard to their ability to function in a terrorist attack (322/431 [74.6%]). Most expressed a low sense of safety with respect to themselves (307/509 [60.4%]) and their relatives (345/507 [67.9%]). Few reported a need for professional help (27/506 [5.3%]). Female sex, sense of safety, and use of tranquilizers, alcohol, and cigarettes to cope were associated with TSR symptoms and symptom criteria for PTSD; level of exposure and objective risk were not. The most prevalent coping mechanisms were active information search about loved ones and social support.Considering the nature and length of the Israeli traumatic experience, the psychological impact may be considered moderate. Although the survey participants showed distress and lowered sense of safety, they did not develop high levels of psychiatric distress, which may be related to a habituation process and to coping mechanisms.
A Polymorphism in HDM2 (SNP309) Associates with Early Onset in Superficial Tumors, TP53 Mutations, and Poor Outcome in Invasive Bladder Cancer
Authors: Marta Sanchez-Carbayo, Nicholas D. Socci, Thomas Kirchoff, Nadina Erill, Keneth Offit, Bernard H. Bochner, Carlos Cordon-Cardo
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The HDM2 gene represents one of the central nodes in the p53 pathway. A recent study reported the association of a single nucleotide polymorphism (SNP309) in the HDM2 promoter region with accelerated tumor formation in both hereditary and sporadic cancers. In this study, we aim to evaluate the SNP309 in bladder cancer and to link it to TP53 status. Experimental Design: SNP309 genotyping and TP53 mutation status were done on 141 bladder tumors and 8 bladder cancer cell lines using a RFLP strategy and TP53 genotyping arrays, respectively. Transcript profiling of a subset of cases (n = 41) was done using oligonucleotide arrays to identify genes differentially expressed regarding their SNP309 status. Results: Of 141 bladder tumors analyzed, 36.9% displayed the SNP309 wild-type (WT; T/T) genotype, whereas 11.3% were homozygous (G/G) and 51.8% were heterozygous (T/G) cases. Patients with superficial disease and the G/G genotype had an earlier age on onset than those with the T/G or T/T genotypes (P = 0.029). Tumors with SNP309 WT genotype significantly displayed TP53 mutations when compared with tumors harboring G/G or T/G genotypes (P &amp;lt; 0.05). SNP309 WT cases had a poorer overall survival than cases with G/G and T/G genotypes (P &amp;lt; 0.05). TP53 mutation status provided enhanced prognostic value (P &amp;lt; 0.001). Transcript profiling identified TP53 targets among those differentially expressed between tumors displaying G/G or T/G SNP309 versus WT cases. Conclusions: SNP309 is a frequent event in bladder cancer, related to earlier onset of superficial disease and TP53 mutation status. SNP309 genotypes were found to be associated with clinical outcome.
Nitrate/nitrite and peroxynitrite in sarcoidosis, related to mycobacteria's stationary-phase
Authors: Anna Dubaniewicz, Leszek Kalinowski, Maria Dudziak, Adam Sternau, Monika Skotarczak
Journal: European Respiratory Journal (2013)

We demonstrated opposite presence of mycobacterial heat shock proteins (Mtb-hsp) 70kDa, 65kDa, 16kDa in sera and lymph nodes in sarcoidosis (SA). We have recently revealed that Mtb-hsp16, Mtb-hsp65, and Mtb-hsp70 concentrations in precipitated immune complexes were significantly higher in SA than in TB and controls. In all tested groups, Mtb-hsp16 concentration was significantly higher than Mtb-hsp70 and Mtb-hsp65. It is possible that in genetically different predisposed hosts, Mtb-hsp16 induced by dose-dependent nitrate⁄nitrite (NOx) may be involved in latent tuberculosis (TB), active TB or SA development. Low level of NOx may result from a rapid reaction of NOx and superoxide with following production of peroxynitrite (ONOO - ). Thus, we evaluated serum NOx and ONOO -  levels in supernatants of PBMC cultures treated with Mtb-hsp from 20 SA patients, 19 TB patients, and 21 healthy volunteers using Griess method and rhodamine fluorescence, respectively. Significantly increased NOx and ONOO -  concentrations with and without Mtb-hsp stimulation were found in SA and TB than in controls, but significantly lower NOx and higher ONOO -  levels after Mtb-hsp induction were shown in SA than TB. In summary, in contrast to active TB, lower level of NOx may induce  M. tuberculosis  genetic dormancy program via higher Mtb-hsp16 expression in SA. Following increased ONOO -  concentration, induced by Mtb-hsp, may explain the low level of NOx and initiate an autoimmune response in SA related to mycobacteria9s stationary-phase.