tbuckley/cabot-search huggingface dataset:
Cilia Formation in Cultures of Human Lung Cancer Cells Treated With Dimethyl Sulfoxide
Authors: Tommie Sue Tralka, Alan S. Rabson
Journal: JNCI Journal of the National Cancer Institute (1976)

Cells from cultures of the ChaGo line of human lung cancer were examined periodically by electron microscopy for 4 years and no cilia were observed. However, when cells were grown in medium containing 2% dimethyl sulfoxide, as many as 50% of the cells had cilia with a 9+0 microtubular pattern.
Impact of a Pre-Emptive Skin Treatment Regimen on Skin Toxicities of Anti–Epidermal Growth Factor Receptor Monoclonal Antibodies: More Questions Than Answers
Authors: Mark Rother
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: The Skin Toxicity Evaluation Protocol With Panitumumab (STEPP) study 1 adds to our increasing knowledge of how best to manage the sometimes troubling dermatologic adverse effects of anti– epidermal growth factor receptor monoclonal antibodies. However, it also raises numerous new questions that need to be addressed before a prophylactic treatment approach becomes a standard of care. As an example, many patients have only mild to no skin toxicity with these drugs. Is preventive therapy really needed in all? Also, the pre-emptive strategy involves four separate interventions. Could just one or two have sufficed? In addition, only one patient (2%) in the reactive treatment group received all four components of the skin treatment regimen when the patient developed a rash. Had these patients received the same protocol as the prophylactic group, would we have seen the same result? The modified Common Terminology Criteria for Adverse Events version 3.0, which was used in this study for the assessment of panitumumab-related skin adverse effects, is a subjective scale. As such, one could question if it is the most appropriate tool to quantify skin toxicity in this unblinded study setting. Finally, severity of rash is highly correlated with the efficacy of these agents. 2-4 Can we be certain this effect will remain in the face of a prophy
The effect of inhaled budesonide on adrenal and growth suppression in asthmatic children
Authors: K. N. Priftis
Journal: European Respiratory Journal (2006)

The present authors evaluated adrenal reserve in asthmatic children on long-term inhaled corticosteroids and whether possible adrenal suppression could be predicted by growth retardation. Low-dose synacthen test (0.5 microg x 1.73 m(-2)) was performed in 72 asthmatic children with a median age of 9.4 (range 4.2-15.7) yrs on long-term treatment (median 18 (range 6-84) months) with low-to-moderate doses (median 363 (range 127-1012) microg x m(-2)) of inhaled budesonide, as well as in 30 controls. Adrenal suppression was considered as a peak serum cortisol <495 nmol x L(-1). The current authors calculated height standard deviation score (HSDS) at the time of testing and height velocity SDS (HVSDS) in the preceding year. Mean HSDS was 0.06+/-1.3 and HVSDS was -0.9+/-2.3. Adrenal suppression was disclosed in 15 asthmatic children (20.8%). There were no differences in HSDS and HVSDS between children with and without adrenal suppression. There was no correlation between peak cortisol response and dose or duration of treatment. However, a positive relationship between HVSDS and duration of treatment was noted. These data suggest that long-term treatment of asthmatic children with low and moderate doses of inhaled budesonide may result in mild adrenal suppression that cannot be predicted by growth deceleration. The negative influence of inhaled corticosteroids on growth becomes less the longer the duration of treatment.
Interaction between endothelin-1 and endothelium-derived relaxing factor in human arteries and veins.
Authors: T F Lüscher, Z Yang, M Tschudi, L von Segesser, P Stulz, C Boulanger, R Siebenmann, M Turina, F R Bühler
Journal: Circulation Research (1990)

Endothelin-1 is a 21-amino acid endothelial vasoconstrictor peptide that may be the physiological antagonist of endothelium-derived relaxing factor (EDRF). Endothelin-1 (10(-11)-3 x 10(-7) M) evoked potent contractions of isolated internal mammary arteries, internal mammary veins, and saphenous veins, which were enhanced in internal mammary veins as compared with internal mammary arteries (concentration shift, 6.3-fold; p less than 0.05) but not in the saphenous veins. Endothelial removal augmented the response to the peptide (at 3 x 10(-7) M) in internal mammary arteries (p less than 0.05) but not in veins. In the artery, EDRF released by acetylcholine or bradykinin reversed endothelin-1-induced contractions; in saphenous veins, both agonists were much less effective compared with the artery and veins contracted with norepinephrine (p less than 0.005-0.01). This inhibition of endothelium-dependent relaxations in veins occurred at half-maximal contractions but was most prominent at maximal contractions to the peptide. Nitric oxide similarly inhibited contractions to endothelin-1 and norepinephrine in internal mammary arteries, whereas in veins that were contracted with endothelin-1 but not with norepinephrine, the relaxations were blunted (p less than 0.005). The nitric oxide donor SIN-1 and sodium nitroprusside induced complete relaxations of internal mammary arteries but were less effective in veins contracted with endothelin-1 (p less than 0.005). Thus, in normal human arteries, EDRF inhibits endothelin-1-induced contractions, whereas the peptide specifically attenuates the effects of EDRF and nitrovasodilators in veins. This may be important in pathological conditions associated with increased levels of endothelin-1 and in veins used as coronary bypass grafts.
Tbx18 function in epicardial development
Authors: Franziska Greulich, Henner F. Farin, Karin Schuster-Gossler, Andreas Kispert
Journal: Cardiovascular Research (2012)

The embryonic epicardium is a source of smooth muscle cells and fibroblasts of the coronary vasculature and of the myocardium, but the molecular circuits that direct the temporal and spatial generation of these cell types from epicardium-derived cells are only partly known. We aimed to elucidate the functional significance of the conserved epicardial expression of the T-box transcription factor gene Tbx18 using transgenic technology in the mouse. We show by cellular and molecular analyses that in Tbx18-deficient mice the epicardium is formed normally and that epicardial cells undergo an epithelial–mesenchymal transition, differentiate into smooth muscle cells and fibroblasts, and form a normal coronary vasculature and fibrous skeleton. Prolonged expression of Tbx18 in epicardium-derived cells by a transgenic approach in vivo does not affect the differentiation and migratory behaviour of these cells. In contrast, epicardial misexpression of a transcriptional activator version of Tbx18, Tbx18VP16, results in premature smooth muscle differentiation of epicardial cells. Inhibition of Notch and transforming growth factor beta receptor signalling in Tbx18VP16 expressing epicardial cells in explant cultures reverts this phenotype. Tbx18 is dispensable for epicardial development, yet a repressive T-box function may be required to prevent premature smooth muscle cell differentiation by repressing transforming growth factor beta receptor and Notch signalling in the embryonic epicardium.
Fluorescence Resonance Energy Transfer–Based Analysis of cAMP Dynamics in Live Neonatal Rat Cardiac Myocytes Reveals Distinct Functions of Compartmentalized Phosphodiesterases
Authors: Marco Mongillo, Theresa McSorley, Sandrine Evellin, Arvind Sood, Valentina Lissandron, Anna Terrin, Elaine Huston, Annette Hannawacker, Martin J. Lohse, Tullio Pozzan, Miles D. Houslay, Manuela Zaccolo
Journal: Circulation Research (2004)

Cardiac myocytes have provided a key paradigm for the concept of the compartmentalized cAMP generation sensed by AKAP-anchored PKA. Phosphodiesterases (PDEs) provide the sole route for degrading cAMP in cells and are thus poised to regulate intracellular cAMP gradients. PDE3 and PDE4 represent the major cAMP degrading activities in rat ventriculocytes. By performing real-time imaging of cAMP in situ, we establish the hierarchy of these PDEs in controlling cAMP levels in basal conditions and on stimulation with a beta-adrenergic receptor agonist. PDE4, rather than PDE3, appears to be responsible for modulating the amplitude and duration of the cAMP response to beta-agonists. PDE3 and PDE4 localize to distinct compartments and this may underpin their different functional roles. Our findings indicate the importance of distinctly localized PDE isoenzymes in determining compartmentalized cAMP signaling.
Prognostic significance of histological grade in clear-cell carcinoma of the ovary: a retrospective study of Korean Gynecologic Oncology Group
Authors: S.-Y. Ryu, S.-I. Park, B.-H. Nam, I. Kim, C.W. Yoo, J.-H. Nam, K.H. Lee, C.-H. Cho, J.-H. Kim, S.Y. Park, B.-G. Kim, S.-B. Kang
Journal: Annals of Oncology (2009)
Real-time imaging of trapping and urease-dependent transmigration of Cryptococcus neoformans in mouse brain
Authors: Meiqing Shi, Shu Shun Li, Chunfu Zheng, Gareth J. Jones, Kwang Sik Kim, Hong Zhou, Paul Kubes, Christopher H. Mody
Journal: Journal of Clinical Investigation (2010)

Infectious meningitis and encephalitis is caused by invasion of circulating pathogens into the brain. It is unknown how the circulating pathogens dynamically interact with brain endothelium under shear stress, leading to invasion into the brain. Here, using intravital microscopy, we have shown that Cryptococcus neoformans, a yeast pathogen that causes meningoencephalitis, stops suddenly in mouse brain capillaries of a similar or smaller diameter than the organism, in the same manner and with the same kinetics as polystyrene microspheres, without rolling and tethering to the endothelial surface. Trapping of the yeast pathogen in the mouse brain was not affected by viability or known virulence factors. After stopping in the brain, C. neoformans was seen to cross the capillary wall in real time. In contrast to trapping, viability, but not replication, was essential for the organism to cross the brain microvasculature. Using a knockout strain of C. neoformans, we demonstrated that transmigration into the mouse brain is urease dependent. To determine whether this could be amenable to therapy, we used the urease inhibitor flurofamide. Flurofamide ameliorated infection of the mouse brain by reducing transmigration into the brain. Together, these results suggest that C. neoformans is mechanically trapped in the brain capillary, which may not be amenable to pharmacotherapy, but actively transmigrates to the brain parenchyma with contributions from urease, suggesting that a therapeutic strategy aimed at inhibiting this enzyme could help prevent meningitis and encephalitis caused by C. neoformans infection.
High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials
Authors: Donald A. Berry, Naoto T. Ueno, Marcella M. Johnson, Xiudong Lei, Jean Caputo, Dori A. Smith, Linda J. Yancey, Michael Crump, Edward A. Stadtmauer, Pierre Biron, John P. Crown, Peter Schmid, Jean-Pierre Lotz, Giovanni Rosti, Marco Bregni, Taner Demirer
Journal: Journal of Clinical Oncology (2011)

High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer.We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients.The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support.Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy.
Functional Compartmentalization of ATP Is Involved in Angiotensin II–Mediated Closure of Cardiac ATP-Sensitive K <sup>+</sup> Channels
Authors: Kunihiko Tsuchiya, Minoru Horie, Masato Watanuki, Carlos A. Albrecht, Kazuhiko Obayashi, Hisayoshi Fujiwara, Shigetake Sasayama
Journal: Circulation (1997)

Background The effects of angiotensin II (Ang II) on ATP-sensitive K + channels (K ATP ) were investigated in ventricular myocytes enzymatically isolated from adult guinea pig heart. Methods and Results In the whole-cell and cell-attached configurations (including open-cell-attached mode) of the patch-clamp technique, K ATP currents ( I KATP ) were activated through metabolic poisoning by the use of inhibitors of both glycolytic and oxidative ATP productions at 37°C. In the whole-cell mode, I KATP were reversibly suppressed by increasing extracellular glucose and Ang II (1 nmol/L). In the cell-attached mode, Ang II concentration-dependently inhibited single K ATP activities with an IC 50 value of 3.2±0.5 pmol/L (Hill coefficient=1.3±0.3). CV11974 (100 nmol/L), an angiotensin 1 (AT 1 ) receptor-selective antagonist, blocked the inhibitory action of Ang II. Preincubation of myocytes with pertussis toxin (5 μg/mL for &gt;120 min at 37°C) virtually prevented subsequent Ang II action. The inhibitory effect of Ang II was also abolished in the open-cell–attached mode (achieved by a prior perfusion of streptolysin- O , 0.08 U/mL). In this mode, through tiny membrane holes, the intracellular ATP concentration can be controlled by bathing extracellular solutions containing a known ATP concentration. Conclusions The inhibitory actions of Ang II on K ATP appear to be mediated by an increase in the subsarcolemmal ATP concentration that results from the inhibition of adenylate cyclase activities via AT 1 receptors/PTX-sensitive G proteins.
Dynamic change of cells expressing MMP-2 mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat
Authors: Tetsu Watanabe, Maki Niioka, Akiko Ishikawa, Shigenari Hozawa, Masao Arai, Katsuya Maruyama, Akiko Okada, Isao Okazaki
Journal: Journal of Hepatology (2001)
Circulating 25-Hydroxyvitamin D, <i>VDR</i> Polymorphisms, and Survival in Advanced Non–Small-Cell Lung Cancer
Authors: Rebecca Suk Heist, Wei Zhou, Zhaoxi Wang, Geoffrey Liu, Donna Neuberg, Li Su, Kofi Asomaning, Bruce W. Hollis, Thomas J. Lynch, John C. Wain, Edward Giovannucci, David C. Christiani
Journal: Journal of Clinical Oncology (2008)

Purpose We showed previously that in early-stage non–small-cell lung cancer (NSCLC), serum vitamin D levels and VDR polymorphisms were associated with survival. We hypothesized that vitamin D levels and VDR polymorphisms may also affect survival among patients with advanced NSCLC. Patients and Methods We evaluated the relationship between circulating 25-hydroxyvitamin D levels; VDR polymorphisms, including Cdx-2 G&gt;A (rs11568820), FokI C&gt;T (rs10735810), and BsmI C&gt;T ( rs144410 ); and overall survival among patients with advanced NSCLC. Analyses of survival outcomes were performed using the log-rank test and Cox proportional hazards models, adjusting for sex, stage, and performance status. Results There were 294 patients and 233 deaths, with median follow-up of 42 months. We found no difference in survival by circulating vitamin D level. The C/C genotype of the FokI polymorphism was associated with improved survival: median survival for C/C was 21.4 months, for C/T was 12.1 months, and for T/T was 15.6 months (log-rank P = .005). There were no significant effects on survival by the Cdx-2 or BsMI polymorphism. However, having increasing numbers of protective alleles was associated with improved survival (adjusted hazard ratio for two or more v zero to one protective alleles, 0.57; 95% CI, 0.41 to 0.79; P = .0008). On haplotype analysis, the G-T-C (Cdx-2-FokI-BsmI) haplotype was associated with worse survival compared with the most common haplotype of G-C-T (adjusted hazard ratio, 1.61; 95% CI, 1.21 to 2.14; P = .001). Conclusion There was no main effect of vitamin D level on overall survival in the advanced NSCLC population. The T allele of the VDR FokI&gt;T polymorphism and the G-T-C (Cdx-2-FokI-BsmI) haplotype were associated with worse survival.
Clinical outcomes and cost-effectiveness of using positive airways pressure to manage sleep apnoea in patients with type 2 diabetes in the UK
Authors: Julian Guest, Monica Panca, Erikas Sladkevicius
Journal: European Respiratory Journal (2013)

Background and aims: To assess clinical outcomes and cost-effectiveness of positive airways pressure (PAP) in managing sleep apnoea patients with type 2 diabetes from the perspective of the UK’s National Health Service (NHS).  Materials and methods: A case-control analysis was conducted using the case records of 150 PAP-treated patients and 150 matched non-PAP treated patients from the THIN database (a nationally representative database of patients registered with general practitioners in the UK). Regression models were used to assess the impact of patients9 baseline variables on resource use and clinical outcomes. The analysis also estimated the cost-effectiveness of PAP compared to no PAP treatment over five years.  Results: Patients’ mean age was 53.7 years, 82% were male and >80% of patients in both groups were obese at 5 years. The time between diagnosis of sleep apnoea and starting PAP treatment was a mean 19.6±31.2 months. Compliance with PAP fell to 89% in year 5. PAP-treated patients had significantly lower HbA1c levels at five years (66.0 versus 118.6 mmol/mol (8.2 versus 13.0%); p  Conclusion: Initiating treatment with PAP in sleep apnoea patients with type 2 diabetes leads to significantly better controlled diabetes and affords a cost-effective use of NHS resources.
Regulation of cardiovascular collagen synthesis by mechanical load
Authors: J Bishop
Journal: Cardiovascular Research (1999)

Time for primary review 20 days. 

The cardiovascular system is constantly exposed to mechanical perturbation from shear and tensile stresses. During development cardiovascular cells respond to changes in mechanical load; growing, dividing and laying down extracellular matrix. Changes in the normal levels of these forces then have further profound effects on these cells resulting in abnormal changes in cardiovascular structure and consequently function. These remodelling processes suggest that the mechanical environment is a key modulator of cell function.

The importance of mechanical forces in the regulation of tissue growth, development and disease has been appreciated for many years. Early studies in the 1960–70s demonstrated, for example, the importance of mechanical load in skeletal muscle growth and development. It was determined that even in the presence of adequate nutrition, and with hormonal and neuronal control, skeletal muscle would not grow without mechanical stimulation [1–3]. The reverse is also true – disuse of a skeletal muscle leads to atrophy [4]. Similarly bone growth and remodelling is dependent on continuous stimuli of pressure and tension [5]. Growth of the lung is also partly regulated by mechanical forces [6]. The response of the cardiovascular system to mechanical stimuli is therefore not unique, however the ability of the cardiovascular system to respond to changes in physical forces by changing the physical properties of the cardiovascular tissues in an attempt to normalise these forces (see Fig. 1) – makes this reciprocal interaction between structure and function and the mechanical environment an extremely fascinating area of study.



Fig. 1 
Reciprocal relation between mechanical forces and cardiovascular remodelling The cardiovascular system responds to changes (Δ) in haemodynamics by cell hypertrophy, proliferation and extracellular matrix deposition. This tissue remodelling results in changes in the physical properties of the tissues which may be sufficient to counteract the altered … 



* Corresponding author. Tel.: +44-171-209-6972; fax: +44-171-209-6973
Beau's ideal
Authors: A. Paton
Journal: BMJ (1988)

from cricket, the picture of Ranji is quite a revelation-a man with the usual human frailities: superstition, extravagance, and an affair as a result of which he left his heart somewhere among the green fields of England. Ross freely quotes from many sources, and fairly extensively too-a method of authorship that may not be very original, but to me this has enriched the book as an authoritative biography. There is an extensive bibliography from which the obsessive cricketer will find good additional reading; and there are a few photographs of Ranji both as a cricketer and a ruler. Reviewing Ranji has given me immense pleasure. For the non-cricketer too the book would be ofconsiderable interest, particularly the second part, evoking nostalgic memories of the Raj as Ross blends east and west with consummate ease. For the cricketer the book is a must. With less than 100 shopping days to go before Christmas, it should be a very popular choice for most Christmas stockings.
Effect of intraduodenal fat on lower oesophageal sphincter function and gastro-oesophageal reflux.
Authors: R H Holloway, E Lyrenas, A Ireland, J Dent
Journal: Gut (1997)

BACKGROUND AND AIMS: Fatty foods are commonly reported to aggravate gastro-oesophageal reflux symptoms. In this study the hypothesis that fat provokes reflux by stimulating transient lower oesophageal sphincter relaxations via small intestinal receptors was investigated. METHODS: In 12 healthy volunteers and 11 patients with reflux oesophagitis, oesophageal motility and pH were measured over 30 minute periods during which saline or fat (10% Intralipid) were infused in random order into the duodenum. The infusion periods were separated by a 30 minute washout. The stomach was loaded with 200 ml 10% dextrose, maintained by an intragastric infusion. RESULTS: Fat decreased basal LOS pressure from 16.9 (SEM 2.1) to 12.4 (SEM 1.5) mm Hg in normal subjects but had no effect in patients with oesophagitis (18.8 (SEM 4.3) v 18.2 (SEM 3.0) mm Hg). During saline infusion, the rates of transient lower oesophageal sphincter relaxation and reflux episodes were greater in patients (4.5 (interquartile range 2-11)/30 min and 5 (2-14)/30 min respectively) than in controls (3 (2-4)/30 min and 3 (2-3.5)/30 min respectively). Fat increased the rate of reflux episodes in the reflux patients to 6.5 (3-25)/30 min. This effect was due to an increase in the incidence of reflux during transient LOS relaxations (65% v 91%), the rate of transient relaxations remaining unchanged. CONCLUSIONS: Instillation of fat directly into the duodenum aggravates reflux in patients with reflux disease, by increasing the proportion of transient LOS relaxations accompanied by reflux.
The evolutionary ecology of metacommunities
Authors: Mark C. Urban, Mathew A. Leibold, Priyanga Amarasekare, Luc De Meester, Richard Gomulkiewicz, Michael E. Hochberg, Christopher A. Klausmeier, Nicolas Loeuille, Claire de Mazancourt, Jon Norberg, Jelena H. Pantel, Sharon Y. Strauss, Mark Vellend, Michael J. Wade
Journal: Trends in Ecology & Evolution (2008)