tbuckley/cabot-search huggingface dataset:
The risk for a cruciate ligament injury of the knee in adolescents and young adults: a population-based cohort study of 46 500 people with a 9 year follow-up
Authors: J Parkkari, K Pasanen, V M Mattila, P Kannus, A Rimpelä
Journal: British Journal of Sports Medicine (2008)

Objectives: The knee joint is the most common site for injury among younger people, the injury often resulting in expensive (surgical) treatment, long-term rehabilitation and permanent functional impairment and disability. Methods: We investigated the incidence and risk factors for a major knee-ligament injury in an adolescent Finnish population. A population-based cohort of 46 472 adolescents was followed for an average of 9 years. All patients hospitalised with the diagnosis of anterior or posterior cruciate ligament injury (ACL or PCL injury) were included in the analysis. Results: 265 (0.6%) people (194 male and 71 female subjects) from the total cohort of 46 472 were treated for a cruciate ligament injury of the knee during the follow-up period, giving an injury incidence of 60.9 (95% CI 53.6 to 68.2) per 100 000 person-years. When the socioeconomic, health and lifestyle background variables were taken into account, the adjusted hazard ratio for a cruciate ligament injury of the knee was 8.5 (95% CI 4.3 to 16.4) for female and 4.0 (95% CI 2.7 to 6.1) for male subjects who participated in organised sports ⩾4 times/week. Conclusions: The general risk for a cruciate ligament injury of the knee is relatively low among adolescents and young adults, but participation in organised sports increases the risk significantly. The risk is especially high in active young women. Preventive measures should be adopted to decrease the short-term and long-term burden of these severe injuries.
Aspirin for the Prevention of Recurrent Venous Thromboembolism
Authors: John Simes, Cecilia Becattini, Giancarlo Agnelli, John W. Eikelboom, Adrienne C. Kirby, Rebecca Mister, Paolo Prandoni, Timothy A. Brighton
Journal: Circulation (2014)

In patients with a first unprovoked venous thromboembolism (VTE) the risk of recurrent VTE remains high after anticoagulant treatment is discontinued. The Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) and the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) trials showed that aspirin reduces this risk, but they were not individually powered to detect treatment effects for particular outcomes or subgroups.An individual patient data analysis of these trials was planned, before their results were known, to assess the effect of aspirin versus placebo on recurrent VTE, major vascular events (recurrent VTE, myocardial infarction, stroke, and cardiovascular disease death) and bleeding, overall and within predefined subgroups. The primary analysis, for VTE, was by intention to treat using time-to-event data. Of 1224 patients, 193 had recurrent VTE over 30.4 months' median follow-up. Aspirin reduced recurrent VTE (7.5%/yr versus 5.1%/yr; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.90; P=0.008), including both deep-vein thrombosis (HR, 0.66; 95% CI, 0.47-0.92; P=0.01) and pulmonary embolism (HR, 0.66; 95% CI, 0.41-1.06; P=0.08). Aspirin reduced major vascular events (8.7%/yr versus 5.7%/yr; HR, 0.66; 95% CI, 0.50-0.86; P=0.002). The major bleeding rate was low (0.4%/yr for placebo and 0.5%/yr for aspirin). After adjustment for treatment adherence, recurrent VTE was reduced by 42% (HR, 0.58; 95% CI, 0.40-0.85; P=0.005). Prespecified subgroup analyses indicate similar relative, but larger absolute, risk reductions in men and older patients.Aspirin after anticoagulant treatment reduces the overall risk of recurrence by more than a third in a broad cross-section of patients with a first unprovoked VTE, without significantly increasing the risk of bleeding.www.anzctr.org.au. Unique identifier: ACTRN12611000684921.
Oxidant Signaling in Vascular Cell Growth, Death, and Survival
Authors: Kaikobad Irani
Journal: Circulation Research (2000)

Abstract —Reactive oxygen species (ROS) have been traditionally regarded as toxic byproducts of aerobic metabolism. However, ROS can also act as intracellular signaling molecules in vascular cells. ROS can mediate phenotypes in vascular endothelial and smooth muscle cells that may be considered both physiological and pathophysiological. Among these are growth, apoptosis, and survival. The specific response elicited by reactive oxygen intermediaries is determined by their specific intracellular target(s). This, in turn, is dependent on the species of oxidant(s) produced, the source and therefore subcellular localization of the oxidant(s), the kinetics of production, and the quantities produced. A fuller understanding of how ROS regulate mitogenesis and apoptosis in vascular smooth muscle and endothelial cells will permit the development of novel strategies to modify or prevent vascular diseases in which these phenotypes predominate.
14-3-3ζ Turns TGF-β’s Function from Tumor Suppressor to Metastasis Promoter in Breast Cancer by Contextual Changes of Smad Partners from p53 to Gli2
Authors: Jia Xu, Sunil Acharya, Ozgur Sahin, Qingling Zhang, Yohei Saito, Jun Yao, Hai Wang, Ping Li, Lin Zhang, Frank J. Lowery, Wen-Ling Kuo, Yi Xiao, Joe Ensor, Aysegul A. Sahin, Xiang H.-F. Zhang, Mien-Chie Hung, Jitao David Zhang, Dihua Yu
Journal: Cancer Cell (2015)
Alternative medicine: cost and subjective benefit in rheumatoid arthritis.
Authors: T Pullar, H A Capell, A Millar, R G Brooks
Journal: BMJ (1982)

Seventy-eight patients with seropositive rheumatoid arthritis were asked about money spent in an attempt to help their arthritis. This included expenditure on alternative medicine, aids for the home, and conventional medicine. Most money was spent on, and most benefit was derived from, aids for the home. Sixty per cent of the patients had tried alternative medicine, but expenditure on this was relatively low and only a small proportion found it helpful.
Cd11b+ myeloid cells support hepatic metastasis through down‐regulation of angiopoietin‐like 7 in cancer cells
Authors: Su Yin Lim, Alex Gordon‐Weeks, Danny Allen, Veerle Kersemans, John Beech, Sean Smart, Ruth J. Muschel
Journal: Hepatology (2015)

Myeloid cells are known to mediate metastatic progression. Here, we attempted to elucidate the mechanisms underlying these effects by identifying gene expression alterations in cancer cells forming hepatic metastases after myeloid cell depletion. Hepatic metastases are heavily infiltrated by CD11b + myeloid cells. We established hepatic metastases in transgenic CD11b‐diphtheria toxin receptor mice by intrasplenic injection of MC38 colon and Lewis lung carcinoma cells before depleting myeloid cells with diphtheria toxin. Myeloid cell depletion inhibited metastatic growth with a marked diminishment of tumor vasculature. Expression of ANGPTL7 (angiopoietin‐like 7), a protein not previously linked to metastasis, was highly up‐regulated in cancer cells after myeloid cell depletion. This effect was duplicated in tissue culture, where coculture of cancer cells with tumor‐conditioned myeloid cells from liver metastases or myeloid cell conditioned media down‐regulated ANGPTL7 expression. Analogous to myeloid cell depletion, overexpression of ANGPTL7 in cancer cells significantly reduced hepatic metastasis formation and angiogenesis. We found that ANGPTL7 itself has strong antiangiogenic effects in vitro . Furthermore, analysis of The Cancer Genome Atlas colorectal and breast cancer data sets revealed striking ANGPTL7 underexpression in cancerous compared to normal tissues. Also, ANGPTL7 was down‐regulated in metastatic liver colonies of colorectal cancer patients compared to their adjacent liver tissue. Conclusion : Myeloid cells promote liver metastasis by down‐regulating ANGPTL7 expression in cancer cells; our findings implicate ANGPTL7 as a mediator of metastatic progression and a potential target for interference with liver metastases. (H epatology 2015;62:521–533
Lack of oral tolerance in C3H/HeJ mice.
Authors: H Kiyono, J R McGhee, M J Wannemuehler, S M Michalek
Journal: The Journal of Experimental Medicine (1982)

Daily gastric intubation of lipopolysaccharide (LPS)-responsive C3H/HeN, BALB/c, and Swiss mice with SRBC for 2 wk resulted in oral tolerance, whereas similarly treated LPS-nonresponsive C3H/HeJ mice gave splenic anti-SRBC PFC responses, including the IgA isotype, after systemic challenge with antigen. Oral tolerance in LPS-responsive C3H/HeN mice was due to T suppressor (Ts) cells because significant Ts cell activity was demonstrated in both Peyer's patches (PP) and spleens of these animals. On the other hand, T cells from PP and spleens of identically treated C3H/HeJ mice exhibited mainly T helper cell activity. Prior treatment of PP or spleen cell preparations from tolerant C3H/HeN mice with anti-Lyt-2.1 resulted in good in vitro anti-SRBC PFC responses, especially IgA isotype responses in PP cell cultures. These results indicate that oral administration of a thymic-dependent antigen (SRBC) to LPS-responsive mice induced a Ts cell population in PP, which, after migration to peripheral lymphoid tissue (e.g., spleen), suppressed responses to systemically administered antigen. LPS-nonresponsive mice lack this Ts cell pathway and continually respond to oral administration of antigen.
Tirapazamine, Cisplatin, and Radiation Versus Cisplatin and Radiation for Advanced Squamous Cell Carcinoma of the Head and Neck (TROG 02.02, HeadSTART): A Phase III Trial of the Trans-Tasman Radiation Oncology Group
Authors: Danny Rischin, Lester J. Peters, Brian O'Sullivan, Jordi Giralt, Richard Fisher, Kally Yuen, Andy Trotti, Jacques Bernier, Jean Bourhis, Jolie Ringash, Michael Henke, Lizbeth Kenny
Journal: Journal of Clinical Oncology (2010)

Purpose Promising results in a randomized phase II trial with the hypoxic cytotoxin tirapazamine (TPZ) combined with cisplatin (CIS) and radiation led to this phase III trial. Patients and Methods Patients with previously untreated stage III or IV (excluding T1-2N1 and M1) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either CIS (100 mg/m 2 ) on day 1 of weeks 1, 4, and 7 or CIS (75 mg/m 2 ) plus TPZ (290 mg/m 2 /d) on day 1 of weeks 1, 4, and 7 and TPZ alone (160 mg/m 2 /d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS). The primary end point was overall survival (OS). The planned sample size was 850, estimated to result in 334 deaths, which would provide 90% power to detect a difference in 2-year survival rates of 60% v 70% for CIS versus TPZ/CIS, respectively (hazard ratio = 0.69). Results Eight hundred sixty-one patients were accrued from 89 sites in 16 countries. In an intent-to-treat analysis, the 2-year OS rates were 65.7% for CIS and 66.2% for TPZ/CIS (TPZ/CIS – CIS: 95% CI, −5.9% to 6.9%). There were no significant differences in failure-free survival, time to locoregional failure, or quality of life as measured by Functional Assessment of Cancer Therapy–Head and Neck. Conclusions We found no evidence that the addition of TPZ to chemoradiotherapy, in patients with advanced head and neck cancer not selected for the presence of hypoxia, improves OS.
Randomized, Blinded Trial Comparing Fondaparinux With Unfractionated Heparin in Patients Undergoing Contemporary Percutaneous Coronary Intervention
Authors: Shamir R. Mehta, Philippe Gabriel Steg, Christopher B. Granger, Jean-Pierre Bassand, David P. Faxon, Jeffrey I. Weitz, Rizwan Afzal, Bonnie Rush, Ron J.G. Peters, Madhu K. Natarajan, James L. Velianou, David M. Goodhart, Marino Labinaz, Jean-Francois Tanguay, Keith A.A. Fox, Salim Yusuf
Journal: Circulation (2005)

Background— Factor Xa plays a central role in the generation of thrombin, making it a novel target for treatment of arterial thrombosis. Fondaparinux is a synthetic factor Xa inhibitor that has been shown to be superior to standard therapies for the prevention of venous thrombosis. We performed a randomized trial to determine the safety and feasibility of fondaparinux in the percutaneous coronary intervention (PCI) setting. Methods and Results— A total of 350 patients undergoing elective or urgent PCI were randomized in a blinded manner to receive unfractionated heparin (UFH), 2.5 mg fondaparinux IV, or 5.0 mg fondaparinux IV. Randomization was stratified for planned or no planned use of glycoprotein (GP) IIb/IIIa antagonists. The primary safety outcome was total bleeding, which was a combination of major and minor bleeding events. The incidence of total bleeding was 7.7% in the UFH group and 6.4% in the combined fondaparinux groups (hazard ratio, 0.81; 95% confidence interval, 0.35 to 1.84; P =0.61). Bleeding was less common in the 2.5-mg fondaparinux group compared with the 5-mg fondaparinux group (3.4% versus 9.6%, P =0.06). The composite efficacy outcome of all-cause mortality, myocardial infarction, urgent revascularization, or need for a bailout GPIIb/IIIa antagonist was 6.0% in the UFH group and 6.0% in the fondaparinux group, with no significant difference in efficacy among the fondaparinux doses compared with UFH. Coagulation marker analysis at 6 and 12 hours after PCI demonstrated that fondaparinux was superior to UFH in inducing a sustained reduction in markers of thrombin generation, as measured by prothrombin fragment F1.2 ( P =0.02). Conclusions— In this pilot study of patients undergoing contemporary PCI, factor Xa inhibition with the synthetic anticoagulant fondaparinux in doses of 2.5 and 5.0 mg was comparable to UFH for clinical safety and efficacy outcomes. These data form the basis for further evaluation of fondaparinux in arterial thrombosis.
A Centennial Review of Neurasthenia
Authors: JOHN C. CHATEL, ROGER PEELE
Journal: American Journal of Psychiatry (1970)

The authors trace the clinical use of the term "neurasthenia," which began 100 years ago, present theories explaining its etiology, and describe its treatment. The term has remained in use in some European countries including France and Russia, but has become virtually obsolete in the United States. Its recent revival in DSM-II has not yet brought about, to the authors' knowledge, any new interest in this concept.
Comparative Effects of Two Ventilatory Modes on Speech in Tracheostomized Patients with Neuromuscular Disease
Authors: Hélène Prigent, Christiane Samuel, Bruno Louis, Marie-France Abinun, Françoise Zerah-Lancner, Michèle Lejaille, Jean-Claude Raphael, Frédéric Lofaso
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Many patients with respiratory failure related to neuromuscular disease receive chronic invasive ventilation through a tracheostomy. Improving quality of life, of which speech is an important component, is a major goal in these patients. We compared the effects on breathing and speech production of assist-control ventilation (ACV) and bilevel positive-pressure ventilation (BPPV) in nine patients with neuromuscular disease. Ventilator-delivered flow was measured using a pneumotachograph, and respiratory rate, inspiratory time, and ventilator-delivered volume were measured on this flow signal. Gas exchange was assessed using oxygen saturation and end-tidal carbon dioxide measurement. Microphone speech recordings were subjected to quantitative analysis. At rest, ventilatory parameters were similar with both modes. Speech induced an increase in inspiratory time during BPPV, with a greater increase in the volume released by the ventilator during speech as compared with ACV (172 +/- 194 versus 26 +/- 31 ml). Consequently, speech duration was longer during inspiration with BPPV. Moreover, BPPV allowed speech production to extend into expiration, and three patients could speak continuously during several respiratory cycles while receiving BPPV. Blood gas exchange was not modified by speech with BPPV or ACV. This study shows that BPPV provides better speech duration than ACV with no detectable short-term deleterious effects.
Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties.
Authors: S Ogawa, H Gerlach, C Esposito, A Pasagian-Macaulay, J Brett, D Stern
Journal: Journal of Clinical Investigation (1990)

Exposure of cultured endothelium to environments with low concentrations of oxygen, in the range of those observed in pathophysiologic hypoxemic states in vivo, compromises cellular barrier and coagulant function. An atmosphere with PO2 approximately 14 mm Hg was not lethally toxic to endothelial cultures, but cells became larger and exhibited small intercellular gaps. At low oxygen concentrations, passage of macromolecular tracers through hypoxic endothelial monolayers was accelerated in a time- and dose-dependent manner, presumably by a paracellular pathway via the gaps. Cell surface coagulant properties of the endothelium were also perturbed. At PO2 approximately 14 mm Hg thrombomodulin antigen and functional activity on the cell surface were diminished by 80-90%, and Northern blots demonstrated suppression of thrombomodulin mRNA. The decrease in thrombomodulin was twice as great compared with the general decline in total protein synthesis in hypoxia. In addition, expression of a direct Factor X activator developed under hypoxic conditions; the activator was membrane-associated and expressed on the surface of intact cultures, Ca-dependent, inhibited by HgCl2 but not PMSF, and had Km approximately 25 micrograms/ml for the substrate at pH 7.4. Synthesis of the activator was blocked by inclusion of cycloheximide, but not warfarin, in the culture medium. These results demonstrate that endothelial function is perturbed in a selective manner in the presence of low concentrations of oxygen, providing insights into mechanisms which may contribute to vascular dysfunction in hypoxemic states.
Anti-apoptogenic function of TGF 1 for human synovial cells: TGF 1 protects cultured synovial cells from mitochondrial perturbation induced by several apoptogenic stimuli
Authors: A Kawakami
Journal: Annals of the Rheumatic Diseases (2003)

To investigate anti-apoptogenic mechanism of transforming growth factor beta1 (TGFbeta1) towards synovial cells.Isolated synovial cells, treated or not with TGFbeta1, were cultured in the presence or absence of anti-Fas IgM, proteasome inhibitor Z-Leu-Leu-Leu-aldehyde (LLL-CHO), etoposide, or C2-ceramide. After cultivation, apoptosis of synovial cells was examined by the presence of hypodiploid DNA(+) cells, the presence of terminal deoxy (d)-UTP nick end labelling(+) cells (TUNEL(+) cells), activation of caspases, and disruption of mitochondrial transmembrane potential (DeltaPsim).Activation of caspase-9 and DeltaPsim was found in anti-Fas IgM treated synovial cells. The increment of both hypodiploid DNA(+) cells and TUNEL(+) cells accompanied by the activation of caspase-8 and caspase-3 was also determined in anti-Fas IgM treated synovial cells. These hallmarks for apoptosis induced by anti-Fas IgM were significantly suppressed in TGFbeta1 treated synovial cells. LLL-CHO, etoposide, and C2-ceramide also caused DeltaPsim, the increment of both hypodiploid DNA(+) cells and TUNEL(+) cells, and the activation of both Leu-Glu-His-Asp ase (LEHDase; caspase-9 like activity) and Asp-Glu-Val-Asp ase (DEVDase; caspase-3 like activity) in synovial cells. As determined in anti-Fas IgM treatment, TGFbeta1 significantly reduced apoptotic cell death of synovial cells induced by the above chemicals.The protective effect of TGFbeta1 for mitochondrial homoeostasis may be important in the anti-apoptogenic function of TGFbeta1 for synovial cells.
Control of the function of substrate-bound C4b-C3b by the complement receptor Cr1.
Authors: M E Medof, V Nussenzweig
Journal: The Journal of Experimental Medicine (1984)

The complement fragments C3b and C4b are the main ligands for the membrane receptor CR1. We showed elsewhere that CR1 functions as an essential cofactor for the factor I-mediated enzymatic breakdown of membrane-bound C3b (*C3b) into C3c and * C3dg . One of the main findings of the present paper is that CR1 also promotes the degradation of bound C4b (*C4b) into C4c and *C4d. On a weight basis, the cofactor activity of CR1 in the cleavage of *C4b present on the cell intermediate EAC14 is 10(3)-fold greater than that of the serum cofactor C4-binding protein ( C4bp ). An additional finding is that the effect of CR1 on either *C3b or *C4b is modulated by the presence of the other ligand in its vicinity; that is, *C4b degradation by CR1 plus I is enhanced by neighboring *C3b and vice versa. For example, upon uptake of optimal amounts of *C3b onto EAC142 and the assembly of the C3-convertase EAC1423 , the activity of CR1 in generating C4c is enhanced 5-10 times further. Conversely, when the number of *C3b molecules on EAC1423 is relatively small (or when EAC1423 has been converted by I plus H into EAC1423i ), the presence of neighboring *C4b enhances the conversion of *C3b (or *iC3b) into C3c plus * C3dg . The enhancing effect of *C3b on the cleavage of *C4b by I is observed only if the cofactor of this reaction is CR1. Indeed, the activity of I or I plus C4bp on *C4b is significantly inhibited when *C3b is fixed and the main product of the reaction is * iC4b . Taken together, these findings suggest that degradation of *C4b will be more effective when enough C3b molecules are fixed nearby, thus facilitating the interaction of *C4b*3b clusters with CR1-bearing cells, and that under physiological conditions, *C4b activity can be efficiently controlled by CR1.
Eyes on 3D‐Current 3D Biomimetic Disease Concept Models and Potential Applications in Age‐Related Macular Degeneration
Authors: Beatrix Feigl, Dietmar Hutmacher
Journal: Advanced Healthcare Materials (2013)

Abstract Three‐dimensional cellular models that mimic disease are being increasingly investigated and have opened an exciting new research area into understanding pathomechanisms. The advantage of 3D in vitro disease models is that they allow systematic and in‐depth studies of physiological and pathophysiological processes with less costs and ethical concerns that have arisen with animal models. The purpose of the 3D approach is to allow crosstalk between cells and microenvironment, and with cues from the microenvironment, cells can assemble their niche similar to in vivo conditions. The use of 3D models for mimicking disease processes such as cancer, osteoarthritis etc., is only emerging and allows multidisciplinary teams consisting of tissue engineers, biologist biomaterial scientists and clinicians to work closely together. While in vitro systems require rigorous testing before they can be considered as replicates of the in vivo model, major steps have been made, suggesting that they will become powerful tools for studying physiological and pathophysiological processes. This paper aims to summarize some of the existing 3D models and proposes a novel 3D model of the eye structures that are involved in the most common cause of blindness in the Western World, namely age‐related macular degeneration (AMD).
The diagnosis and management of gastric cancer: expert discussion and recommendations from the 12th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2010
Authors: E. Van Cutsem, M. Dicato, R. Geva, N. Arber, Y. Bang, A. Benson, A. Cervantes, E. Diaz-Rubio, M. Ducreux, R. Glynne-Jones, A. Grothey, D. Haller, K. Haustermans, D. Kerr, B. Nordlinger, J. Marshall, B.D. Minsky, Y.K. Kang, R. Labianca, F. Lordick, A. Ohtsu, N. Pavlidis, A. Roth, P. Rougier, H.J. Schmoll, A. Sobrero, J. Tabernero, C. Van de Velde, J. Zalcberg
Journal: Annals of Oncology (2011)