tbuckley/cabot-search huggingface dataset:
Does laser lithotripsy hit the target?
Authors: M L WILKINSON
Journal: Gut (1998)

See article on page 823 

Ever since it was generally concluded that endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy was the treatment of choice for choledocholithiasis, big bile duct stones have remained a major challenge for the endoscopist. Extending a sphincterotomy increases risk of bleeding and perforation, mechanical lithotripters are generally expensive, cumbersome to use, fragile, and fail to grasp the stones effectively in a significant proportion of cases. Intraduct solvents such as mono octanoin or methyl tert butyl ether are ineffectual or dangerous, or both. The somewhat defeatist approach of placing stents in elderly patients can lead to stent migration with occasional serious consequences or the formation of multiple stones above the stent, with the consequent risk of further cholangitis. There is probably a place at a few referral centres for extracorporeal shock wave lithotripsy (ESWL) but this requires some sort of biliary catheter to deliver x ray contrast medium to facilitate targeting, which usually means at least two ERCPs in addition to the lithotripsy sessions. Furthermore, not all stones fragment easily and the capital costs and low usage mean that endoscopists must borrow sessions from their …
Activated macrophages release a factor which lyses malignant cells but not normal cells.
Authors: G A Currie, C Basham
Journal: The Journal of Experimental Medicine (1975)

When rat macrophages are activated by exposure to bacterial endotoxin they acquire the capacity to lyse sarcoma cells in tissue culture. Although showing no immunological specificity this lytic effect was only detectable on malignant cells; normal cells were unaffected. This tumor-selective lytic effect is mediated by a labile supernatant product.
PML suppresses oncogenic transformation of NIH/3T3 cells by activated neu.
Authors: J H Liu, Z M Mu, K S Chang
Journal: The Journal of Experimental Medicine (1995)

The chromosomal translocation t(15;17)(q22;q12) is a consistent feature of acute promyelocytic leukemia (APL) that results in the disruption of genes for the zinc finger transcription factor PML and the retinoic acid receptor alpha (RAR alpha). We have previously shown that PML is a growth suppressor and is able to suppress transformation of NIH/3T3 by activated neu oncogene. In the study presented here, the full-length PML cDNA was transfected into B104-1-1 cells (NIH/3T3 cells transformed by the activated neu oncogene) by retrovirally mediated gene transfer. We found that expression of PML could reverse phenotypes of B104-1-1 including morphology, contact-limiting properties, and growth rate in both transient-expression and stable transfectants. We also demonstrated that PML is able to suppress clonogenicity of B104-1-1 in soft agar assay and tumorigenicity in nude mice. These results strongly support our previous finding that PML is a transformation or growth suppressor. Our results further demonstrate that expression of PML in B104-1-1 cells has little effect on cell cycle distribution. Western blot analysis demonstrated that suppression of neu expression in B104-1-1 by PML was insignificant in the transient transfection experiment but significant in the PML stable transfectants. This study suggests that PML may suppress neu expression and block signaling events associated with activated neu. This study supports our hypothesis that disruption of the normal function of PML, a growth or transformation suppressor, is a critical event in APL leukomogenesis.
Gender Differences in Outcomes After Primary Angioplasty Versus Primary Stenting With and Without Abciximab for Acute Myocardial Infarction
Authors: Alexandra J. Lansky, Cody Pietras, Ricardo A. Costa, Yoshihiro Tsuchiya, Bruce R. Brodie, David A. Cox, Eve D. Aymong, Thomas D. Stuckey, Eulogio Garcia, James E. Tcheng, Roxana Mehran, Manuela Negoita, Martin Fahy, Ecaterina Cristea, Mark Turco, Martin B. Leon, Cindy L. Grines, Gregg W. Stone
Journal: Circulation (2005)

Background— Women with acute myocardial infarction (AMI) undergoing primary angioplasty have higher rates of morbidity and mortality than do men. Whether contemporary interventional treatment strategies have improved outcomes for women compared with men is unknown. Methods and Results— In the CADILLAC trial, 2082 patients (27% women) with AMI within 12 hours of symptom onset were randomized to balloon angioplasty (PTCA; n=518), PTCA+abciximab (n=528), stenting (n=512), and stenting+abciximab (n=524). As compared with men, women had a lower body surface area; had a greater prevalence of diabetes, hypertension, and hyperlipidemia; experienced significant delays to treatment; and had better baseline and final TIMI grade 3 flows. Unadjusted 1-year event rates were higher for women, including death (7.6% versus 3.0%, P &lt;0.001), ischemic target-vessel revascularization (TVR; 16.7% versus 12.1%, P =0.006), and major adverse cardiac events (MACE; 23.9% versus 15.3%, P &lt;0.001). Female gender was an independent predictor of MACE and bleeding complications, although comorbid risk factors and body surface area but not gender predicted 1-year death. For women, primary stenting resulted in a reduction in 1-year MACE from 28.1% to 19.1% ( P =0.01) and in ischemic TVR from 20.4% to 10.8% ( P =0.002) compared with PTCA. The addition of abciximab to primary stenting significantly reduced the 30-day ischemic TVR without increasing bleeding or stroke rates. Conclusions— The higher mortality rate in women compared with men after interventional treatment for AMI may be explained by differences in body size and clinical risk factors, although female gender remains an important independent determinant of overall adverse outcomes. For women in the CADILLAC trial, the addition of abciximab reduced 30-day TVR without increasing bleeding risk, and primary stenting reduced 1-year TVR and MACE rates compared with PTCA.
Controversies in the Evaluation and Management of Chronic Cough
Authors: Surinder S. Birring
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Section:ChooseTop of pageAbstract <<GASTROESOPHAGEAL REFLUX–A...UPPER AIRWAYS COUGH SYNDR...COUGH VARIANT ASTHMAUNEXPLAINED CHRONIC COUGH...LIMITATIONS OF THE CURREN...THE NEW COUGH PARADIGM: C...ASSESSMENT OF COUGH SEVER...CONCLUSIONSReferencesCITING ARTICLES
The price of the CD27–CD70 costimulatory axis: you can't have it all
Authors: Martijn A. Nolte, René A.W. van Lier
Journal: The Journal of Experimental Medicine (2006)

T cells require costimulatory signals for optimal proliferation, differentiation, and survival and thus to induce protective immune responses. Recent data, however, show that during chronic lymphocyte choriomeningitis virus (LCMV) infection, triggering of the costimulatory receptor CD27 by its ligand CD70 impedes neutralizing antibody production and leads to viral persistence. Thus, while being crucial for the induction of some adaptive effector pathways, costimulation may block the development of others. Pathogens may exploit this Achilles' heal to achieve persistence.
Drug-Eluting Stent and Coronary Thrombosis
Authors: Thomas F. Lüscher, Jan Steffel, Franz R. Eberli, Michael Joner, Gaku Nakazawa, Felix C. Tanner, Renu Virmani
Journal: Circulation (2007)

Although rare, stent thrombosis remains a severe complication after stent implantation owing to its high morbidity and mortality. Since the introduction of drug-eluting stents (DES), most interventional centers have noted stent thrombosis up to 3 years after implantation, a complication rarely seen with bare-metal stents. Some data from large registries and meta-analyses of randomized trials indicate a higher risk for DES thrombosis, whereas others suggest an absence of such a risk. Several factors are associated with an increased risk of stent thrombosis, including the procedure itself (stent malapposition and/or underexpansion, number of implanted stents, stent length, persistent slow coronary blood flow, and dissections), patient and lesion characteristics, stent design, and premature cessation of antiplatelet drugs. Drugs released from DES exert distinct biological effects, such as activation of signal transduction pathways and inhibition of cell proliferation. As a result, although primarily aimed at preventing vascular smooth muscle cell proliferation and migration (ie, key factors in the development of restenosis), they also impair reendothelialization, which leads to delayed arterial healing, and induce tissue factor expression, which results in a prothrombogenic environment. In the same way, polymers used to load these drugs have been associated with DES thrombosis. Finally, DES impair endothelial function of the coronary artery distal to the stent, which potentially promotes the risk of ischemia and coronary occlusion. Although several reports raise the possibility of a substantially higher risk of stent thrombosis in DES, evidence remains inconclusive; as a consequence, both large-scale and long-term clinical trials, as well as further mechanistic studies, are needed. The present review focuses on the pathophysiological mechanisms and pathological findings of stent thrombosis in DES.
Molecular Pathways: The Complexity of the Epigenome in Cancer and Recent Clinical Advances
Authors: Mariarosaria Conte, Lucia Altucci
Journal: Clinical Cancer Research (2012)

Human cancer is causally linked to genomic and epigenomic deregulations. Epigenetic abnormalities occurring within signaling pathways regulating proliferation, migration, growth, differentiation, transcription, and death signals may be critical in the progression of malignancies. Consequently, identification of epigenetic marks and their bioimplications in tumors represents a crucial step toward defining new therapeutic strategies both in cancer treatment and prevention. Alterations of writers, readers, and erasers in cancer may affect, for example, the methylation and acetylation state of huge areas of chromatin, suggesting that epi-based treatments may require "distinct" therapeutic strategies compared with "canonical" targeted treatments. Whereas anticancer treatments targeting histone deacetylase and DNA methylation have entered the clinic, additional chromatin modification enzymes have not yet been pharmacologically targeted for clinical use in patients. Thus, a greater insight into alterations occurring on chromatin modifiers and their impact in tumorigenesis represents a crucial advancement in exploiting epigenetic targeting in cancer prevention and treatment. Here, the interplay of the best known epi-mutations and how their targeting might be optimized are addressed.
Efficacy of Pamidronate for Osteoporosis in Patients with Cystic Fibrosis following Lung Transplantation
Authors: ROBERT M. ARIS, GAYLE E. LESTER, JORDAN B. RENNER, ANDREW WINDERS, A. DENENE BLACKWOOD, ROBERT K. LARK, DAVID A. ONTJES
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Lung transplantation with its attendant life-long immunosuppression contributes to bone loss and its sequelae, fractures and kyphosis, in patients with lung disease, many of whom already suffer from severe osteoporosis. Patients with cystic fibrosis (CF) are one of the most severely affected groups. We conducted a controlled, randomized, nonblinded trial of pamidronate (30 mg intravenously every 3 mo) with vitamin D (800 IU/d) and calcium (1 g/d) (n = 16) compared with vitamin D and calcium alone (n = 18, the control subjects) for 2 yr in 34 patients after lung transplant to improve bone mineral density (BMD). The treatment groups were similar in age, sex, baseline T-scores, renal function, hospitalization rates, immunosuppressant levels, change in lung function, and body mass index (BMI) over the study period. The patients treated with pamidronate gained 8.8 ± 2.5% and 8.2 ± 3.8% in spine and femur BMD after 2 yr in comparison to control subjects, who gained, on average ( ± SD), 2.6 ± 3.2 and 0.3 ± 2.2%, respectively (p ⩽ 0.015 for both). Seven and six fractures occurred in the control and pamidronate groups, respectively (p > 0.2). Measures of bone resorption were highest immediately after lung transplant and improved with both pamidronate and time. Measures of bone formation were very poor after lung transplant, but recovered in the first post-lung transplant year irrespective of therapy. We conclude that pamidronate was more effective than control in improving bone mineral density after lung transplantation in patients with CF and appears to be one of the most promising agents studied to date for posttransplant osteoporosis.
Beyond brain regions: Network perspective of cognition–emotion interactions
Authors: Luiz Pessoa
Journal: Behavioral and Brain Sciences (2012)

Lindquist et al. provide a convincing case against what they call the locationist account of emotion. Their quantitative approach elegantly illustrates the shortcomings of this still-entrenched viewpoint. Here, I discuss how a network perspective will advance our understanding of structure-function mappings in general, and the relationship between emotion and cognition in the brain.
Airborne lipid antigens mobilize resident intravascular NKT cells to induce allergic airway inflammation
Authors: Seth T. Scanlon, Seddon Y. Thomas, Caroline M. Ferreira, Li Bai, Thomas Krausz, Paul B. Savage, Albert Bendelac
Journal: The Journal of Experimental Medicine (2011)

Airborne exposure to microbial cell wall lipids such as lipopolysaccharide triggers innate immune responses that regulate susceptibility to allergic airway inflammation. α-Glycosylceramides represent another widespread class of microbial lipids that directly stimulate innate-like, IL-4– and IL-13–producing, CD1d-restricted NKT cells. In this study, we demonstrate that NKT cells constitutively accumulate and reside in the microvasculature of the mouse lung. After a single airborne exposure to lipid antigen, they promptly extravasate to orchestrate the formation of peribronchiolar and interstitial lymphohistiocytic granulomas containing numerous eosinophils. Concomitant airborne exposure to ovalbumin (OVA) induces the priming of OVA-specific Th2 cells and IgE antibodies by the same dendritic cell coexpressing CD1d and MHC class II. Although NKT cell activation remains confined to the lipid-exposed lung and draining lymph nodes, Th2 cells recirculate and seed the lung of a parabiotic partner, conferring susceptibility to OVA challenge months after the initial exposure, in a manner independent of NKT cells and CD1d. Thus, transient recruitment and activation of lung-resident intravascular NKT cells can trigger long-term susceptibility to allergic airway inflammation.
Reducing Risk by Improving Standards of Intrapartum Fetal Care
Authors: Peter Young, Rosie Hamilton, Sheena Hodgett, Mary Moss, Claire Rigby, Peter Jones, Richard Johanson
Journal: Journal of the Royal Society of Medicine (2001)

Summary Confidential Enquiries into Stillbirths and Deaths in Infancy (CESDI) have pointed to a high frequency of suboptimal intrapartum fetal care of a kind that, in the event of an adverse outcome, is hard to defend in court. In an effort to minimize liability, various strategies were applied in a district hospital labour ward—guidelines, cyclical audit, monthly feedback meetings and training sessions in cardiotocography (CTG). The effects of these interventions on quality of care was assessed by use of the CESDI system in all babies born with an Apgar score of 4 or less at 1 min and/or 7 or less at 5 min. 540 babies (4.3%) had low Apgar scores, and neither the percentage nor gestational age differed significantly between audit periods. In the baseline audit, care was judged suboptimal (grade II/III) in 14 (74%) of 19 cases, and in the next four periods it was 23%, 27%, 27% and 32%. In the latest audit period, after further educational interventions, it was 9%. Many of the failures to recognize or act on abnormal events were related to CTG interpretation. After the interventions there was a significant increase in cord blood pH measurement. There were no differences between audit periods in the proportion of babies with cord pH &lt;7.2. These results indicate that substantial improvements in quality of intrapartum care can be achieved by a programme of clinical riskmanagement.
Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3 degradation
Authors: Yan Xiu, Hao Xu, Chen Zhao, Jinbo Li, Yoshikazu Morita, Zhenqiang Yao, Lianping Xing, Brendan F. Boyce
Journal: Journal of Clinical Investigation (2013)

The cytokines RANKL and TNF activate NF-κB signaling in osteoclast precursors (OCPs) to induce osteoclast (OC) formation. Conversely, TNF can limit OC formation through NF-κB p100, which acts as an inhibitor, and TNF receptor–associated receptor 3 (TRAF3); however, a role for TRAF3 in RANKL-mediated OC formation is unknown. We found that TRAF3 limits RANKL-induced osteoclastogenesis by suppressing canonical and noncanonical NF-κB signaling. Conditional OC-specific Traf3-KO (cKO) mice had mild osteoporosis and increased OC formation. RANKL induced TRAF3 degradation via the lysosome/autophagy system. The autophagy/lysosome inhibitor chloroquine reduced RANKL-induced OC formation and function by increasing TRAF3 expression in OCPs in vitro and in vivo. Although chloroquine had no effect on basal bone resorption, it inhibited parathyroid hormone– and ovariectomy-induced OC activation in WT, but not cKO, mice. Deletion of the transcription factor gene Relb resulted in increased TRAF3 expression in OCPs, which was associated with decreased RANKL-induced TRAF3 degradation. RelB directly increased expression of BECN1, a key autophagy regulator, by binding to its promoter. These data indicate that autophagic/lysosomal degradation of TRAF3 is an important step in RANKL-induced NF-κB activation in OCPs. Furthermore, treatments that increase TRAF3 levels in OCPs, including pharmacological inhibition of its degradation with compounds such as chloroquine, may limit bone destruction in common bone diseases.
Health-Related Quality of Life Parameters As Prognostic Factors in a Nonmetastatic Breast Cancer Population: An International Multicenter Study
Authors: Fabio Efficace, Patrick Therasse, Martine J. Piccart, Corneel Coens, Kristel Van Steen, Marzena Welnicka-Jaskiewicz, Tanja Cufer, Jaroslaw Dyczka, Michail Lichinitser, Lois Shepherd, Hanneke de Haes, Mirjam A. Sprangers, Andrew Bottomley
Journal: Journal of Clinical Oncology (2004)

Purpose The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages. Patients and Methods The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty. Results The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P = .03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis. Conclusion Our findings suggest that baseline HRQOL parameters have no prognostic value in a nonmetastatic breast cancer population.
Hemolytic Uremic Syndrome
Authors: Stefan Heinen, Mihály Józsi, Andrea Hartmann, Marina Noris, Giuseppe Remuzzi, Christine Skerka, Peter F. Zipfel
Journal: Journal of the American Society of Nephrology (2007)

Defective complement regulation results in hemolytic uremic syndrome (HUS), a disease that is characterized by microangiopathy, thrombocytopenia, and acute renal failure and that causes endothelial cell damage. For characterization of how defective complement regulation relates to the pathophysiology, the role of the complement regulator factor H and also of a mutant factor H protein was studied on the surface of human umbilical vein endothelial cells. The mutant 145-kD factor H protein was purified to homogeneity, from plasma of a patient with HUS, who is heterozygous for a factor H gene mutation G3587T, which introduces a stop codon at position 1172. Functional analyses show that the lack of the most C-terminal domain short consensus repeats 20 severely affected recognition functions (i.e., binding to heparin, C3b, C3d, and the surface of endothelial cells). Wild-type factor H as well as the mutant protein formed dimers in solution as shown by cross-linking studies and mass spectroscopy. When assayed in fluid phase, the complement regulatory activity of the mutant protein was normal and comparable to wild-type factor H. However, on the surface of endothelial cells, the mutant factor H protein showed severely reduced regulatory activities and lacked protective functions. Similarly, with the use of sheep erythrocytes, the mutant protein lacked the protective activity and caused increased hemolysis when it was added to factor H-depleted plasma. This study shows how a mutation that affects the C-terminal region of the factor H protein leads to defective complement control on cell surfaces and damage to endothelial cells in patients with HUS. These effects explain how mutant factor H causes defective complement control and in HUS-particularly under condition of inflammation and complement activation-causes endothelial cell damage.