tbuckley/cabot-search huggingface dataset:
The five-repetition sit-to-stand test as a functional outcome measure in COPD
Authors: Sarah E Jones, Samantha S C Kon, Jane L Canavan, Mehul S Patel, Amy L Clark, Claire M Nolan, Michael I Polkey, William D-C Man
Journal: Thorax (2013)

<h3>Background</h3> Moving from sitting to standing is a common activity of daily living. The five-repetition sit-to-stand test (5STS) is a test of lower limb function that measures the fastest time taken to stand five times from a chair with arms folded. The 5STS has been validated in healthy community-dwelling adults, but data in chronic obstructive pulmonary disease (COPD) populations are lacking. <h3>Aims</h3> To determine the reliability, validity and responsiveness of the 5STS in patients with COPD. <h3>Methods</h3> Test-retest and interobserver reliability of the 5STS was measured in 50 patients with COPD. To address construct validity we collected data on the 5STS, exercise capacity (incremental shuttle walk (ISW)), lower limb strength (quadriceps maximum voluntary contraction (QMVC)), health status (St George9s Respiratory Questionnaire (SGRQ)) and composite mortality indices (Age Dyspnoea Obstruction index (ADO), BODE index (iBODE)). Responsiveness was determined by measuring 5STS before and after outpatient pulmonary rehabilitation (PR) in 239 patients. Minimum clinically important difference (MCID) was estimated using anchor-based methods. <h3>Results</h3> Test-retest and interobserver intraclass correlation coefficients were 0.97 and 0.99, respectively. 5STS time correlated significantly with ISW, QMVC, SGRQ, ADO and iBODE (r=−0.59, −0.38, 0.35, 0.42 and 0.46, respectively; all p&lt;0.001). Median (25th, 75th centiles) 5STS time decreased with PR (Pre: 14.1 (11.5, 21.3) vs Post: 12.4 (10.2, 16.3) s; p&lt;0.001). Using different anchors, a conservative estimate for the MCID was 1.7 s. <h3>Conclusions</h3> The 5STS is reliable, valid and responsive in patients with COPD with an estimated MCID of 1.7 s. It is a practical functional outcome measure suitable for use in most healthcare settings.
Temporal effects of cigarette smoke associated to diesel exhaust particles in mice
Authors: Petra M.M. Arantes, Alessandra C. Toledo, Francine M. Almeida, Clarice R. Olivo, Renato M. Magalhães, Ligia R. Fornaziero, Mariangela Macchione, Paulo H.N. Saldiva, Paolo J.C. Biselli, Fernanda D.T.Q.S. Lopes, Mílton A. Martins
Journal: European Respiratory Journal (2011)

Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD), since 80% of COPD cases are associated to long term smoking. Diesel exhaust particles (DEP) are a major source of traffic-related air pollution and it is a risk factor to the development of this disease. The aim of this study was to evaluate the time course of the effects of CS associated to DEP exposure on the development of emphysema at 1, 3 and 6 months. Mice were divided into 5 groups: control (C); vehicle (V) NaCl 0.9%; DEP -nasal instillation of 30μg DEP in 10μl NaCl 0.9%/day, 5days/wk; CS - exposed to CS for 30min/day, 5days/wk; and group DEP+CS. We evaluated inflammatory cells in bronchoalveolar lavage (BAL) and mean linear intercept (Lm). We observed a increase in Lm values after 6 mo. in groups CS, DEP and DEP+CS (p≤0.001). Temporal analysis of cell profile in BAL showed an increase in total cells in 3 mo. after CS exposure (p≤0.001), while at 6 mo. we observed a decrease in DEP+CS group compared to C, CS and DEP (p≤0.001). Same cell profile was noted in macrophages numbers (p≤0.001). Decrease in lymphocytes was observed at 3 mo. in DEP and DEP+CS compared to CS (p=0.001).

View this table:

Linear intercept after 6 months of exposure





Therefore independently which exogenous particles were inhaled: CS or DEP, the pulmonary emphysema developed after 6 mo. and did not show an impairment by exposition to both. After 6 mo. we observed a synergic effect of DEP+CS leading to an attenuation of the density of inflammatory cells in BAL. Our data suggest that exposition to DEP could result in the development of COPD.
Mutations of <i>β-Catenin</i> in Adrenocortical Tumors: Activation of the Wnt Signaling Pathway Is a Frequent Event in both Benign and Malignant Adrenocortical Tumors
Authors: Frédérique Tissier, Catherine Cavard, Lionel Groussin, Karine Perlemoine, Gwladys Fumey, Anne-Marie Hagneré, Fernande René-Corail, Eric Jullian, Christine Gicquel, Xavier Bertagna, Marie-Cécile Vacher-Lavenu, Christine Perret, Jérôme Bertherat
Journal: Cancer Research (2005)

Abstract Adrenocortical cancer is a rare cancer with a very poor prognosis. The genetic alterations identified to date in adrenocortical tumors are limited. Activating mutations of the Wnt signaling pathway have been observed in more frequent cancers, particularly digestive tract tumors. We investigated whether Wnt pathway activation is involved in adrenocortical tumorigenesis. In a series of 39 adrenocortical tumors, immunohistochemistry revealed abnormal cytoplasmic and/or nuclear accumulation of β-catenin in 10 of 26 adrenocortical adenomas and in 11 of 13 adrenocortical carcinomas. An activating somatic mutation of the β-catenin gene was shown in 7 of 26 adrenocortical adenomas and in 4 of 13 adrenocortical carcinomas; these mutations were observed only in adrenocortical tumors with abnormal β-catenin accumulation and most were point mutations altering the Ser45 of exon 3 (in the consensus GSK3-β/CK1 phosphorylation site). Functional studies showed that the activating Ser45 β-catenin mutation found in the adrenocortical cancer H295R cell line leads to constitutive activation of T-cell factor–dependent transcription. This is the first molecular defect to be reported with the same prevalence in both benign (27%) and malignant (31%) adrenocortical tumors. β-Catenin mutations are also the most frequent genetic defect currently known in adrenocortical adenomas. In adrenocortical adenomas, β-catenin alterations are more frequent in nonfunctioning tumors, suggesting that β-catenin pathway activation might be mostly involved in the development of nonsecreting adrenocortical adenomas and adrenocortical carcinomas. The very frequent and substantial accumulation of β-catenin in adrenocortical carcinomas suggests that other alterations might also be involved. This finding may contribute to new therapeutic approaches targeting the Wnt pathway in malignant adrenocortical tumors, for which limited medical therapy is available.
Histologic Improvement of Fibrosis in Patients with Hepatitis C Who Have Sustained Response to Interferon Therapy
Authors: Yasushi Shiratori, Fumio Imazeki, Mitsuhiko Moriyama, Michitami Yano, Yasuyuki Arakawa, Osamu Yokosuka, Tetsuo Kuroki, Shuhei Nishiguchi, Michio Sata, Gotarou Yamada, Shigetoshi Fujiyama, Haruhiko Yoshida, Masao Omata
Journal: Annals of Internal Medicine (2000)

Background: Short-term histologic improvement in hepatitis C-related hepatic fibrosis has been noted in studies with more than 2 years of follow-up, but the long-term effects of interferon therapy on hepatic fibrosis remain unclear. Objective: To assess changes in hepatic fibrosis after interferon therapy in patients with chronic hepatitis C. Design: Retrospective cohort study. Setting: 7 university hospitals and 1 national hospital in Japan. Patients: 593 patients with chronic hepatitis C who underwent a paired liver biopsy from 1987 to 1997. Of these, 487 patients received interferon therapy and 106 patients were untreated. Intervention: Patients in the treatment group received a 2- to 6-month course of interferon within 6 months after the initial biopsy. Measurements: Fibrosis and inflammatory activity in paired biopsy samples obtained a median of 3.7 years apart (range, 1 to 10 years) were graded by using the criteria of Desmet and colleagues (F0 to F4) and those of the French METAVIR Cooperative Study Group (A0 to A3), respectively. Changes in fibrosis staging and activity scores and yearly rates of fibrosis progression and regression were calculated. Results: 183 of the 487 interferon-treated patients showed a sustained virologic response. Activity grade was unchanged in most of the untreated patients and improved in 89% (CI, 83% to 93%) of patients with a sustained virologic response. A sustained response to interferon was associated with a mean (±SE) reduction in fibrosis score of −0.60 ± 0.07 at less than 3 years of follow-up and −0.88 ± 0.08 at 3 years or more of follow-up. The rate of fibrosis progression was −0.28 ± 0.03 unit/y (regression) in patients with sustained response, 0.02 ± 0.02 unit/y in patients with nonsustained response (P < 0.001), and 0.10 ± 0.02 unit/y in untreated patients. Conclusion: Although the time between biopsies partly affected the patient's clinical course, the differences observed here suggest that in patients with chronic hepatitis C, regression of fibrosis is associated with sustained virologic response to interferon therapy.
Targeting Tumor-Infiltrating Macrophages Decreases Tumor-Initiating Cells, Relieves Immunosuppression, and Improves Chemotherapeutic Responses
Authors: Jonathan B. Mitchem, Donal J. Brennan, Brett L. Knolhoff, Brian A. Belt, Yu Zhu, Dominic E. Sanford, Larisa Belaygorod, Danielle Carpenter, Lynne Collins, David Piwnica-Worms, Stephen Hewitt, Girish Mallya Udupi, William M. Gallagher, Craig Wegner, Brian L. West, Andrea Wang-Gillam, Peter Goedegebuure, David C. Linehan, David G. DeNardo
Journal: Cancer Research (2012)

Tumor-infiltrating immune cells can promote chemoresistance and metastatic spread in aggressive tumors. Consequently, the type and quality of immune responses present in the neoplastic stroma are highly predictive of patient outcome in several cancer types. In addition to host immune responses, intrinsic tumor cell activities that mimic stem cell properties have been linked to chemoresistance, metastatic dissemination, and the induction of immune suppression. Cancer stem cells are far from a static cell population; rather, their presence seems to be controlled by highly dynamic processes that are dependent on cues from the tumor stroma. However, the impact immune responses have on tumor stem cell differentiation or expansion is not well understood. In this study, we show that targeting tumor-infiltrating macrophages (TAM) and inflammatory monocytes by inhibiting either the myeloid cell receptors colony-stimulating factor-1 receptor (CSF1R) or chemokine (C-C motif) receptor 2 (CCR2) decreases the number of tumor-initiating cells (TIC) in pancreatic tumors. Targeting CCR2 or CSF1R improves chemotherapeutic efficacy, inhibits metastasis, and increases antitumor T-cell responses. Tumor-educated macrophages also directly enhanced the tumor-initiating capacity of pancreatic tumor cells by activating the transcription factor STAT3, thereby facilitating macrophage-mediated suppression of CD8(+) T lymphocytes. Together, our findings show how targeting TAMs can effectively overcome therapeutic resistance mediated by TICs.
Injuries in whitewater kayaking
Authors: D C Fiore, J D Houston
Journal: British Journal of Sports Medicine (2001)

Objective —To provide epidemiological data on whitewater kayaking injuries using a descriptive study. Methods —A retrospective survey was distributed at whitewater events and club meetings, and made available and advertised on the world wide web, through postings and announcements to newsgroups, related sites, and search engines. Data on sex, age, experience, and ability were collected. Injury data collected included mechanism, activity, difficulty of rapid, and self reported severity. Results —Of the 392 kayaking respondents included in the final analysis, 219 suffered 282 distinct injury events. The number of days spent kayaking per season was the only independent predictor of injury. The overwhelming majority of injuries occurred while the kayaker was still in the boat (87%). Striking an object was the most common mechanism of injury (44%), followed by traumatic stress and overuse (25% each). The most common types of injury were abrasion (25%), tendinitis (25%), contusion (22%), and dislocation (17%). The upper extremity, especially the shoulder, was the most commonly injured area of the body. Although half of injured kayakers sought medical care for their injury, and almost one third missed more than one month of kayaking because of the injury, almost all (96%) reported a complete or good recovery. Conclusions —Factors relating to likelihood of injury appear to be connected with exposure, namely the number of days a year that the sport was pursued. Except for class V (extreme) kayakers, reports of injuries paralleled the number of participants. Kayakers reported injuries predominantly on rivers that they assessed to be at a level appropriate to their skills.
The Effect of Insulin Antibodies on the Metabolic Action of Inhaled and Subcutaneous Insulin
Authors: Tim Heise, Susanne Bott, Corinna Tusek, Jens-Armin Stephan, Tom Kawabata, Deborah Finco-Kent, Cameron Liu, Alan Krasner
Journal: Diabetes Care (2005)

OBJECTIVE—To assess the impact of the development of high- or low-affinity insulin antibodies (IABs) on postprandial glucose tolerance, duration of insulin action, and clinical safety in patients with type 1 diabetes receiving inhaled insulin (Exubera). RESEARCH DESIGN AND METHODS—This study consisted of a prospective, randomized, open-label, parallel-group trial in which 47 patients with type 1 diabetes received NPH insulin twice daily plus either premeal inhaled insulin (INH group; n = 24) or premeal subcutaneous regular insulin (SC group; n = 23) for 24 weeks. Meal challenge and euglycemic clamp studies were performed on consecutive days at baseline, week 12, and week 24. Adverse events were monitored. RESULTS—For the INH and SC groups, mean (±SD) IAB levels were 3.5 ± 3.9 and 2.6 ± 4.1 μU/ml at baseline, respectively, compared with 101.4 ± 140.4 and 4.3 ± 9.4 μU/ml at week 24. At week 24, the changes from baseline were similar for the INH and SC groups for maximal plasma glucose concentration (Cmax) (adjusted ratio for treatment group difference 0.99 [90% CI 0.95–1.03]), area under the plasma glucose concentration time curve (adjusted ratio for treatment group difference 0.98 [0.88–1.08]), and duration of insulin action (adjusted treatment group difference 29 min [−49 to 108]). No adverse events were attributed to IABs. CONCLUSIONS—In patients with type 1 diabetes treated with inhaled insulin, development of high- or low-affinity IABs did not impair postprandial glucose tolerance, alter the time-action profile of insulin, or impact tolerability. No clinical relevance of IABs was identified in this study.
Origins of the<i>E. coli</i>Strain Causing an Outbreak of Hemolytic–Uremic Syndrome in Germany
Authors: David A. Rasko, Dale R. Webster, Jason W. Sahl, Ali Bashir, Nadia Boisen, Flemming Scheutz, Ellen E. Paxinos, Robert Sebra, Chen-Shan Chin, Dimitris Iliopoulos, Aaron Klammer, Paul Peluso, Lawrence Lee, Andrey O. Kislyuk, James Bullard, Andrew Kasarskis, Susanna Wang, John Eid, David Rank, Julia C. Redman, Susan R. Steyert, Jakob Frimodt-Møller, Carsten Struve, Andreas M. Petersen, Karen A. Krogfelt, James P. Nataro, Eric E. Schadt, Matthew K. Waldor
Journal: New England Journal of Medicine (2011)

A large outbreak of diarrhea and the hemolytic-uremic syndrome caused by an unusual serotype of Shiga-toxin-producing Escherichia coli (O104:H4) began in Germany in May 2011. As of July 22, a large number of cases of diarrhea caused by Shiga-toxin-producing E. coli have been reported--3167 without the hemolytic-uremic syndrome (16 deaths) and 908 with the hemolytic-uremic syndrome (34 deaths)--indicating that this strain is notably more virulent than most of the Shiga-toxin-producing E. coli strains. Preliminary genetic characterization of the outbreak strain suggested that, unlike most of these strains, it should be classified within the enteroaggregative pathotype of E. coli.We used third-generation, single-molecule, real-time DNA sequencing to determine the complete genome sequence of the German outbreak strain, as well as the genome sequences of seven diarrhea-associated enteroaggregative E. coli serotype O104:H4 strains from Africa and four enteroaggregative E. coli reference strains belonging to other serotypes. Genomewide comparisons were performed with the use of these enteroaggregative E. coli genomes, as well as those of 40 previously sequenced E. coli isolates.The enteroaggregative E. coli O104:H4 strains are closely related and form a distinct clade among E. coli and enteroaggregative E. coli strains. However, the genome of the German outbreak strain can be distinguished from those of other O104:H4 strains because it contains a prophage encoding Shiga toxin 2 and a distinct set of additional virulence and antibiotic-resistance factors.Our findings suggest that horizontal genetic exchange allowed for the emergence of the highly virulent Shiga-toxin-producing enteroaggregative E. coli O104:H4 strain that caused the German outbreak. More broadly, these findings highlight the way in which the plasticity of bacterial genomes facilitates the emergence of new pathogens.
Abstract 2586: Pomegranate components modulate distinct pathways in prostate cancer cells
Authors: Radha Munagala, Farrukh Aqil, Ramesh C. Gupta, Richard M. Higashi, Manicka V. Vadhanam
Journal: Cancer Research (2012)

Abstract Pomegranate juice, when provided as whole juice, modulates specific pathways in prostate cancer cells that are not reflected when its major constituents were tested independently. In order to identify these bioactive components of pomegranate, the peel (P) and arils (J) were isolated, juiced separately and extracted with 80% methanol (PE and JE). The components were enriched using a SPE C18 cartridge and, eluted as fraction I (P-I and J-I - contains mostly polar compounds) and fraction II (P-II and J-II - contains mostly non-polar compounds). Analysis by HPLC-PDA and by direct infusion analysis of these fractions by FTICR-MS revealed the J-I consisted of mostly phenolics including the three anthocyanins in its mono- and di-glycoside forms. P-I consisted mostly of punicalin and, the punicalagins A and B, while P-II and J-II consisted mostly of ellagitannins and free ellagic acid. The ORAC values as Trolox equivalent for the various fractions at 10 µg/ml were: Total peel extract (PE) - 1.64 compared with 2.74 for P-I and 4.01 for P-II, while for the total juice extract (JE) it was 2.62 compared with 7.01 for J-I and 5.47 for J-II. To identify the molecular mechanisms, the individual fractions of peel and juice were tested in prostate cancer cell lines, LNCaP and PC3 and analyzed by Cancer/Apoptosis Phospho Antibody Array and western blot analysis. In LNCaP cell line, BCL-2, PTEN, Cdc25A, p53 and STAT6 were hyper-phosphorylated by J-II, while they were unaltered by J-I. Similarly, GSK3 alpha and beta were hyper-phosphorylated by J-I and unmodified by J-II. When peel fractions were tested, Cdc25C, BCL-2, CREB and JAK were hypo-phosphorylated by P-II, whereas they were unaltered by P-I. Other molecules, such as IRS-1, MAP Kinase, PTEN, STAT3 and JAK2 were hypo-phosphorylated by P-II, and were hyper-phosphorylated by P-I. In PC3 cell line, BCL-2, p53 and CREB were hypo-phosphorylated by J-II, while they were unaltered by J-I. However, PTEN and p70 were hypo-phosphorylated by J-II and hyper-phosphorylated by J-I, while, CDK2, STATs 1, 3 and 6 were hypo-phosphorylated by P-II, they were unaltered by P-I fraction. Thus the components of peel and juice fractions demonstrate unique properties and the ability to modulate distinct pathways in androgen-dependent and independent prostate cancer cells providing a rich set of potential therapy or adjuvant applications. This work is supported by NCI grant CA143676. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2586. doi:1538-7445.AM2012-2586
Trends in prevalence of symptoms of asthma, hay fever, and eczema in 12-14 year olds in the British Isles, 1995-2002: questionnaire survey
Authors: H Ross Anderson, Ruth Ruggles, David P Strachan, Jane B Austin, Michael Burr, David Jeffs, Peter Standring, Andrea Steriu, Rosie Goulding
Journal: BMJ (2004)

suspicious for metastatic disease, however, would have resulted in an unacceptably low sensitivity of 20%.Considering the high incidence of bone metastases at initial diagnosis, this might lead to a dramatic increase in the number of patients undergoing futile surgery or neoadjuvant chemotherapy.Contributors: MH had the original idea, designed the study, selected the patients, managed the study, interpreted the results, wrote the first draft of the paper, and edited the paper.JH gathered, interviewed, and examined the patients.CA interpreted the bone scans; gathered, interviewed, and physically examined the patients; interpreted the results, and prepared the manuscript.KN interpreted the magnetic resonance images.HS had the original idea, interpreted the bone scans, and prepared the manuscripts.
Anti-IL-23 Monoclonal Antibody Synergizes in Combination with Targeted Therapies or IL-2 to Suppress Tumor Growth and Metastases
Authors: Michele W.L. Teng, Bianca von Scheidt, Helene Duret, Jennifer E. Towne, Mark J. Smyth
Journal: Cancer Research (2011)

Immunosuppressive barricades erected by tumors during the evolution of immune escape represent a major obstacle to many potentially effective cancer therapies and vaccines. We have shown that host interleukin (IL)-23 suppresses the innate immune response during carcinogenesis and metastasis, independently of effects on the proinflammatory cytokine IL-17A. Based on these findings, we envisioned that IL-23 neutralization might offer a promising strategy to modulate immunosuppression, particularly in combination with immunostimulatory agents. Here we show that by itself a neutralizing monoclonal antibody (mAb) to IL-23 suppressed early experimental lung metastases in the B16F10 mouse model of melanoma and also modestly inhibited the subcutaneous growth of primary tumors. These antitumor effects were respectively mediated by natural killer cells or CD8(+) T cells. More notably, combinatorial treatments of anti-IL-23 mAb with IL-2 or anti-erbB2 mAb significantly inhibited subcutaneous growth of established mammary carcinomas and suppressed established experimental and spontaneous lung metastases. Overall, our results suggest the potential of anti-human IL-23 mAbs to improve the immunostimulatory effects of IL-2 and trastuzumab in the current management of some advanced human cancers.
Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth
Authors: Chrystelle Lamagna, Kairbaan M. Hodivala-Dilke, Beat A. Imhof, Michel Aurrand-Lions
Journal: Cancer Research (2005)

Abstract The junctional adhesion molecule-C (JAM-C) was recently described as an adhesion molecule localized at interendothelial contacts and involved in leukocyte transendothelial migration. The protein JAM-C interacts with polarity complex molecules and regulates the activity of the small GTPase Cdc42. The angiogenesis process involves rearrangement of endothelial junctions and implicates modulation of cell polarity. We tested whether JAM-C plays a role in angiogenesis using tumor grafts and hypoxia-induced retinal neovascularization. Treatment with a monoclonal antibody directed against JAM-C reduces tumor growth and infiltration of macrophages into tumors. The antibody decreases angiogenesis in the model of hypoxia-induced retinal neovascularization in vivo and vessel outgrowth from aortic rings in vitro. Importantly, the antibody does not induce pathologic side effects in vivo. These findings show for the first time a role for JAM-C in angiogenesis and define JAM-C as a valuable target for antitumor therapies.