tbuckley/cabot-search huggingface dataset:
Additive anti-inflammatory effect of formoterol and budesonide on human lung fibroblasts
Authors: F M Spoelstra
Journal: Thorax (2002)

It has been shown that treatment with a long acting beta2 agonist in addition to a glucocorticoid is beneficial in the treatment of asthma. In asthma inflammatory cells, particularly eosinophils, migrate into the pulmonary tissue and airway lumen by means of adhesion molecules expressed on resident tissue cells--that is, fibroblasts--and become activated by cytokines and adhesive interactions. A study was undertaken to determine whether an interaction exists between the long acting beta2 agonist formoterol and the glucocorticoid budesonide on inhibition of adhesion molecule expression, as well as chemo/cytokine production by human lung fibroblasts.Lung fibroblasts were preincubated with therapeutically relevant drug concentrations of 10(-8) M to 10(-10) M. Cells were stimulated with interleukin (IL)-1beta (1 or 10 U/ml) for 8 hours and supernatants were collected for measurement of GM-CSF and IL-8 concentrations. The cells were fixed and subjected to a cell surface ELISA technique to measure the expression of ICAM-1 and VCAM-1.Formoterol exerted an additive effect on the inhibition of IL-1beta stimulated ICAM-1 and VCAM-1 upregulation and GM-CSF production by budesonide in concentrations of 10(-9) M and above (p<0.05). IL-8 production was not influenced by formoterol.Formoterol exerts an additive effect on the anti-inflammatory properties of budesonide. In vitro data support the finding that the combination of budesonide and formoterol in asthma treatment strengthens the beneficial effect of either drug alone.
Effect of the two tachykinin antagonists, SR 48968 and SR 140333, on cough induced by citric acid in the unanaesthetized guinea pig
Authors: V Girard, E Naline, P Vilain, X Emonds-Alt, C Advenier
Journal: European Respiratory Journal (1995)

It is now well-established that sensory nerves stimulation in the airway induces bronchoconstriction and inflammation, but also protective reflexes, such as coughing. These effects are mediated through the release of tachykinins (substance P and neurokinin A) and we have recently shown that SR 48968, a tachykinin NK2-receptor antagonist, inhibited cough induced by citric acid. In this paper, we have studied the effects of SR 48968 administered by aerosol. We have also investigated the effects of SR 140333, a tachykinin NK1-receptor antagonist, and the combination of both SR 48968 and SR140333 to determine whether tachykinin NK1 receptors are involved in cough. Finally, we have studied the combined effects of SR 48968 and salbutamol to find out whether the antitussive effect of SR 48968 is a consequence of the inhibition of bronchoconstriction. Unanaesthetized guinea-pigs were placed in a transparent chamber and exposed to an aerosol of citric acid (0.4 M). The number of coughs was counted by visual inspection and by determination of sounds and pressure variations in the chamber. By the aerosol route, SR 48968 was an efficient antitussive and 16 times more potent than codeine. SR 140333 (0.1-1 mg.kg-1 i.p.) did not exert any antitussive effect but it potentiated the maximal effect induced by SR 48968. Finally, salbutamol, in a dose (0.3 mg.kg-1) which inhibits bronchoconstriction, but not cough induced by citric acid, did not modify the antitussive effect of SR 48968.(ABSTRACT TRUNCATED AT 250 WORDS)
Targeted Ablation of PINCH1 and PINCH2 From Murine Myocardium Results in Dilated Cardiomyopathy and Early Postnatal Lethality
Authors: Xingqun Liang, Yunfu Sun, Maoqing Ye, Maria C. Scimia, Hongqiang Cheng, Jody Martin, Gang Wang, Ann Rearden, Chuanyue Wu, Kirk L. Peterson, Henry C. Powell, Sylvia M. Evans, Ju Chen
Journal: Circulation (2009)

Background— PINCH proteins are 5 LIM domain–only adaptor proteins that function as key components of the integrin signaling pathway and play crucial roles in multiple cellular processes. Two PINCH proteins, PINCH1 and PINCH2, have been described in mammals and share high homology. Both PINCH1 and PINCH2 are ubiquitously expressed in most tissues and organs, including myocardium. Cardiac-specific PINCH1 knockout or global PINCH2 knockout mice exhibit no basal cardiac phenotype, which may reflect a redundant role for these 2 PINCH proteins in myocardium. A potential role for PINCH proteins in myocardium remains unknown. Methods and Results— To define the role of PINCH in myocardium, we generated mice that were doubly homozygous null for PINCH1 and PINCH2 in myocardium. Resulting mutants were viable at birth but developed dilated cardiomyopathy and died of heart failure within 4 weeks. Mutant hearts exhibited disruptions of intercalated disks and costameres accompanied by fibrosis. Furthermore, multiple cell adhesion proteins exhibited reduced expression and were mislocalized. Mutant cardiomyocytes were significantly smaller and irregular in size. In addition, we observed that the absence of either PINCH1 or PINCH2 in myocardium leads to exacerbated cardiac injury and deterioration in cardiac function after myocardial infarction. Conclusions— These results demonstrate essential roles for PINCHs in myocardial growth, maturation, remodeling, and function and highlight the importance of studying the role of PINCHs in human cardiac injury and cardiomyopathy.
Heart Rate–Independent Vagal Effect on End-Systolic Elastance of the Canine Left Ventricle Under Various Levels of Sympathetic Tone
Authors: Yasunori Nakayama, Hiroshi Miyano, Toshiaki Shishido, Masashi Inagaki, Toru Kawada, Masaru Sugimachi, Kenji Sunagawa
Journal: Circulation (2001)

Background Although we have shown that in rabbits the direct (heart rate [HR]–independent) vagal effect on left ventricular end-systolic elastance (E es ) was negligible under minimal sympathetic tone, how underlying sympathetic tone modulates the inotropic response to vagal stimulation remains unknown. Methods and Results We used an isolated canine heart preparation with functioning autonomic nerves. We examined the direct vagal inotropic effect by measuring E es under fixed-rate atrial pacing with or without concomitant sympathetic nerve stimulation. Right and left vagal stimulation at 20 Hz decreased HR by 27±3% and 14±2%, respectively, and decreased E es by 11±2% and 6±2%, respectively. When we fixed HR by atrial pacing, right and left vagal stimulation at 20 Hz did not decrease E es (0.01±0.3% and 0.3±0.4%; NS). Concomitant left sympathetic nerve stimulation at 4 Hz enhanced direct vagal negative inotropism to −19±3% and −34±5% for 20-Hz right and left vagal stimulation (interaction, P &lt;0.01). Conclusions Direct vagal negative inotropism was unobservable with minimal sympathetic tone in dogs but was enhanced with concomitant sympathetic stimulation.
A Health Economic Model to Assess the Long-Term Effects and Cost-Effectiveness of Orlistat in Obese Type 2 Diabetic Patients
Authors: Mark Lamotte, Lieven Annemans, Aurelia Lefever, Myriam Nechelput, Johan Masure
Journal: Diabetes Care (2002)

OBJECTIVES—Obesity is a common condition in type 2 diabetic patients. Treating obesity may enhance hypoglycemic treatment and contribute to the reduction of long-term microvascular and macrovascular complications. Orlistat reduces cardiovascular risk factors in obese type 2 diabetic patients. The objectives of this study were to estimate the long-term clinical consequences of this weight loss and the resulting cost-effectiveness of treating obese type 2 diabetic patients with orlistat. RESEARCH DESIGN AND METHODS—A Markov model was developed to predict, over a 10-year period, the complication rates and mortality with and without a 2-year orlistat treatment, assuming a 5-year catch-up period after treatment. A stepwise approach was used to obtain the clinical data. First, the impact of weight loss with orlistat on HbA1c, blood pressure, and cholesterol was assessed; then, the impact on mortality and micro- and macrovascular complications of decreasing these risk factors was applied. Four subgroups were studied based on the presence of risk factors. RESULTS—Cost-effectiveness varies between 3,462 Euro/life-year gained (LYG) for obese diabetic patients with hypertension and hypercholesterolemia and 19,986 Euro/LYG for obese diabetic patients without other risk factors. The latter result is not robust according to sensitivity analyses. CONCLUSIONS—Our results suggest that orlistat is cost-effective in the management of obese type 2 diabetic patients, especially in those with the presence of hypercholesterolemia and/or hypertension. Evidence on longer-term benefits of orlistat (&amp;gt;2 years) will be of importance for future decision-making.
p27Kip1 is an independent predictor of recurrence after surgical resection in patients with small hepatocellular carcinoma
Authors: Carolina Armengol, Loreto Boix, Oriol Bachs, Manel Solé, Josep Fuster, Margarita Sala, Josep M Llovet, Juan Rodés, Jordi Bruix
Journal: Journal of Hepatology (2003)
1059-6 The multicenter evaluation of the everolimus-eluting stent for inhibition of neointimal hyperplasia: Results of the pooled FUTURE I and II trials
Authors: Ricardo A Costa, Alexandra J Lansky, Roxana Mehran, Yoshihiro Tsuchiya, Ecaterina Cristea, Yeal Gilutz, Maria Coral, Manuela Negoita, Ramona Pop, Michael Rink, Ralf Muller, George Techen, Eberhard Grube
Journal: Journal of the American College of Cardiology (2004)
Can we use video images to triage pigmented lesions?
Authors: V.M.L. Jolliffe, D.W. Harris, R. Morris, P. Wallace, S.J. Whittaker
Journal: British Journal of Dermatology (2001)

Advances in telemedicine permit consultations where the doctor and patient are at different sites.To determine whether this technology could be used to triage referrals of pigmented lesions to a dermatology out-patient clinic, and thereby assist in managing the ever increasing number of lesions being referred.When patients attended clinic, a clinical diagnosis of their pigmented lesion was made and recorded. A still image of each lesion was subsequently taken from a video camera using a PC card, and stored. These images were subsequently viewed in conjunction with the general practitioner's referral information and designated as 'warrants referral' or 'does not warrant referral'. For each lesion this decision was compared with the clinical diagnosis made during the live consultation in the clinic (the 'gold standard'). Clinical diagnoses designated as warranting referral were malignant melanoma, basal cell carcinoma, keratoacanthoma, atypical naevus and pyogenic granuloma (due to the potential clinical confusion with amelanotic melanoma). Lesions that were not considered to warrant referral included benign melanocytic naevus, seborrhoeic keratosis, dermatofibroma, congenital naevus, solar lentigo, actinic keratosis and various other benign conditions.In total, 819 lesions were evaluated, resulting in a mean sensitivity of 81% and specificity of 73% for the technique.We feel that the overall sensitivity of 81% is encouraging as regards the use of such a technique as a triage tool, but that the inability to examine the whole patient or palpate the lesions is a major drawback in the safe triage of patients with pigmented lesions.
Angiotensin responsiveness in hyperfiltering and nonhyperfiltering diabetic rats.
Authors: B M Wilkes, P F Mento, M A Vernace
Journal: Journal of the American Society of Nephrology (1993)

Renal and systemic responses to angiotensin II were studied in hyperglycemic diabetic rats (streptozotocin, 60 mg/kg, i.v.) and vehicle-injected controls at 24 h, 1 wk, 2 mo, or at 6 to 12 mo. In normal rats, the GFR was less than 0.80 mL/min per 100 g body wt (0.57 +/- 0.02 mL/min per 100 g body wt; range: 0.40 to 0.79 mL/min per 100 g body wt; N = 45). Hyperfiltration (GFR > or = 0.80 mL/min per 100 g body wt) was observed in all diabetic rats studied at 1 wk (GFR, 1.03 +/- 0.07 mL/min per 100 g body wt; N = 5; P < 0.001 versus control). However, at earlier and later times, GFR was elevated in only 8 of 18 of the diabetic rats (44%), with an overall prevalence of 56% (13 of 23). Mean arterial pressure, plasma glucose, urine volume, and filtration fraction were not different in hyperfiltering diabetic rats compared with nonhyperfiltering diabetic rats or normal controls. Angiotensin II (12.5 ng/kg per minute i.v.) had no effect on GFR in normal rats or nonhyperfiltering diabetic rats, but it normalized GFR in hyperfiltering diabetic rats (0.74 +/- 0.05 mL/min per 100 g body wt). In contrast with the renal effects of angiotensin II, blood pressure responses were similar in hyperfiltering and nonhyperfiltering diabetic rats. The findings that angiotensin II infusion caused a greater fall in GFR in hyperfiltering diabetic rats than in nonhyperfiltering diabetic rats, but that blood pressure responses were similar, suggests a localized abnormality in angiotensin responsiveness in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
S110 Targeted deletion of G q/G 11 in surfactant protein C-positive epithelial cells reduces TGFss activation and results in inflammation and alveolar airspace enlargement
Authors: A. E. John, A. Habgood, J. Porte, A. Tatler, L. Jolly, S. Offermanns, R. G. Jenkins
Journal: Thorax (2011)

Activation of latent TGFß by the epithelially-restricted αvß6 integrin is critical in the pathogenesis of lung injury and fibrosis, and disruption of this pathway promotes emphysema development. We have previously shown that Gαq and RhoA signalling pathways are central to avb6 integrin induced TGFß activation in vitro. To assess the role of the Gq/11 signalling pathway in the lungs, we generated mice with deletion of the Gq and G11 α-subunits in Surfactant protein C (SftpC)-positive epithelial cells (Gq/11DKO). SftpC-Cre mice were crossed with constitutive Gα11-deficient animals (<i>Gna11</i><sup>−/−</sup>; G11KO) carrying floxed alleles of the Gaq gene (<i>Gnaq<sup>fl/fl</sup></i>) and then backcrossed onto appropriate null mice. Lungs were perfused, inflated and fixed prior to processing for histological and immunohistochemical analysis at 2, 4, 6 and 8 weeks. Bronchoalveolar lavage (BAL) cells were collected at 6 weeks for mRNA, nuclear protein extraction or histological analysis. Focal inflammatory infiltrates were visible in the Gq/11DKO lungs as early as 2 weeks, but became larger and more widespread at later timepoints. Gq/11DKO mice also exhibited significant age-related airspace enlargement compared with G11KO mice from 4 weeks onwards. From 6 weeks, inflammation was closely associated with localised disruption of the alveolar architecture and the appearance of enlarged and vacuolated macrophages within the airspaces. BAL fluid from Gq/11DKO mice contained significantly higher cells numbers (12.5±2.5×10<sup>5</sup>) than G11KO mice (0.96±0.2×10<sup>5</sup>) with increases in the percentage of neutrophils, lymphocytes and enlarged and vacuolated alveolar macrophages. mRNA analysis of Gq/11DKO BAL cells showed significantly increased MMP12, RELMα and Arginase 1 suggesting an increase in the number of alternatively activated macrophages. To assess levels of active TGFß in the lungs, phosphorylated SMAD2 (pSMAD2), a component of the TGFß signalling pathway, was measured by ELISA of nuclear extracts from BAL cells. Gq/11DKO BAL cells contained significantly lower levels of pSMAD2 than those from G11KO mice, suggesting decreased levels of active TGFß in the lungs of Gq/11DKO mice. These data suggest that the Gαq/11 signalling pathway in SftpC-positive epithelial cells regulates TGFß activation in the lungs and that deficiency in this pathway results in pulmonary inflammation and disruption of the alveolar architecture of the lung.
Commentaries on this month's Cardiovascular Controversy: the merits and demerits of animal experimentation From M Frank
Authors: M. Frank
Journal: Cardiovascular Research (1994)

Journal Article Commentaries on this month's Cardiovascular Controversy: the merits and demerits of animal experimentation From M Frank Get access Martin Frank Martin Frank Executive Director, The American Physiological Society, 9650 Rockville Pike, Bethesda, MD, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 7, July 1994, Page 1108, https://doi.org/10.1093/cvr/28.7.1108a Published: 01 July 1994
Genome-wide association study identifies multiple loci influencing human serum metabolite levels
Authors: Johannes Kettunen, Taru Tukiainen, Antti-Pekka Sarin, Alfredo Ortega-Alonso, Emmi Tikkanen, Leo-Pekka Lyytikäinen, Antti J Kangas, Pasi Soininen, Peter Würtz, Kaisa Silander, Danielle M Dick, Richard J Rose, Markku J Savolainen, Jorma Viikari, Mika Kähönen, Terho Lehtimäki, Kirsi H Pietiläinen, Michael Inouye, Mark I McCarthy, Antti Jula, Johan Eriksson, Olli T Raitakari, Veikko Salomaa, Jaakko Kaprio, Marjo-Riitta Järvelin, Leena Peltonen, Markus Perola, Nelson B Freimer, Mika Ala-Korpela, Aarno Palotie, Samuli Ripatti
Journal: Nature Genetics (2012)
Cold urticaria and virus infections: a clinical and serological study in 39 patients
Authors: H.M.G. DOEGLAS, W.J. RIJNTEN, F.P. SCHRODER, J. SCHIRM
Journal: British Journal of Dermatology (1986)

Thirty-nine patients with cold urticaria seen over a 12-year-period were re-examined. All but 12 still had positive skin tests for cold and only five of these had shown a spontaneous cure. Fourteen patients were prone to collapse on cold exposure. The incidence of atopy in this group was comparable to that in control groups. Cold urticaria is an extremely chronic disease. The mean disease duration was 9.3 years. Serum antibodies to Epstein-Barr virus, measles virus, cytomegalovirus (CMV), varicella-zoster virus (VZV), herpes simplex virus (HSV), Chlamydia psittaci and Mycoplasma pneumoniae were determined in all 39 patients and compared with control groups. The EBV-antibody patterns (heterophile antibodies and different types of EBV-specific antibodies) showed no evidence of current or of recent primary or secondary infection with EBV. Complement fixing antibody titres to measles virus, CMV, HSV and Mycoplasma pneumoniae were significantly higher in cold urticaria patients than in controls. The existence of a basic immuno-regulatory defect responsible for both the cold urticaria and the elevated antibody levels is proposed.
Pulling the Trigger
Authors: Frank L. Meyskens, John H. Fetting
Journal: Journal of Clinical Oncology (2004)

VOLUME 22 䡠 NUMBER 17 䡠 SEPTEMBER 1 2004 J OURNAL OF C LINICAL O NCOLOGY T H E A R T O F O N C O L O G Y: When the Tumor Is Not the Target Pulling the Trigger Frank L. Meyskens Jr and John H. Fetting From the Comprehensive Cancer Center, University of California Irvine, Orange, CA; and The Johns Hopkins Oncology Center, Baltimore, MD. Submitted May 3, 2004; accepted May 7, 2004. Authors’ disclosures of potential con- flicts of interest are found at the end of this article. Address reprint requests to Frank L. Meyskens Jr, MD, Comprehensive Cancer Center, University of California Irvine, 101 City Dr S, Orange, CA; e-mail: flmeyske@uci.edu. © 2004 by American Society of Clinical Oncology 0732-183X/04/2217-3644/$20.00 DOI: 10.1200/JCO.2004.04.046 It’s near the end The interminable end Your suffering has been unbearable Many months have gone by ...and you just won’t die. No more visitors: Your friends were first then your family your ex the white coats and eventually, even the nurses... except for one nurse, and she is only here because the guilt of your daughter was too great. You asked me to put you to sleep forever, to give you an easy death. But how could you know that 20 years ago I shook violently at the moment the barbiturate hit the brain of our 16 year old miniature poodle His bright eyes faded, and closed, his puppy-like head slumped on my chest. For many days thereafter, quite unexpectedly, I cried in private many times But my sadness I could not hide My kids asked: “What’s wrong Dad?” “What’s wrong Dad?” And long walks, holding hands, enjoying simple things, being more a dad than usual was the only answer I could ever give. Even today, twenty years later, when the end is near and interminable and you, my patient, asks me to kill you: my eyes mist, my soul aches. My answer always is: You, as one who suffers, might well deserve that option, but I, as a doctor, can never be the one who pulls the trigger, to become your executioner. “For taking away the suffering” may be the lure for those who would be gods But I, as a doctor, am just flesh and blood. For those who talk so causally about euthanasia as just another medical procedure or intervention have been there when the light departs into the void And there is a shutter in the universe. Frank L. Meyskens Jr Father’s Day, June 15, 2003 Commentary This poem describes a physician and a patient pushed to their limits. They have fought to relieve the patient’s suffering, but have been frustrated. Both long for the pa- tient’s death. It is at this desperate moment that the patient asks to be euthanized. The physician, reflecting on a past euthanasia, in- dicates that he will not do it, that he cannot do it—not for this patient, not for any patient. In spare, unflinchingly honest language, Frank Meyskens describes the awful suffering Information downloaded from jco.ascopubs.org and provided by UNIV OF CALIFORNIA IRVINE on December 22, 2014 from 128.200.104.165. Copyright © 2004 by the American Society of Clinical Oncology. All rights reserved.
Dual asymmetries in handedness
Authors: Gregory V. Jones, Maryanne Martin
Journal: Behavioral and Brain Sciences (2003)

The possibility that two forms of asymmetry underlie handedness is considered. Corballis has proposed that right-handedness developed when gesture encountered lateralized vocalization but may have been superimposed on a preexisting two-thirds dominance. Evidence is reviewed here which suggests that the baseline asymmetry is even more substantial than this, with possible implications for brain anatomy and genetic theories of handedness.
Cetuximab Is Contraindicated in the Perioperative Treatment of Colorectal Liver Metastases
Authors: John N. Primrose, David Cunningham, O. James Garden, Tim S. Maughan, Siân A. Pugh, Louise Stanton, Stephen J. Falk, Myrddin Rees, Meg Finch-Jones, Juan W. Valle, Derek O'Reilly, Joanne Hornbuckle, Tamas Hickish, John A. Bridgewater
Journal: Journal of Clinical Oncology (2015)
Defeated yet defiant
Authors: Liam Farrell
Journal: BMJ (2008)

“Hurrah for Captain Spaulding,” I carolled as the door opened, which I thought quite droll, because his name, can you believe it, was Joe Spaulding. But the infectious bonhomie of Groucho Marx proved no defence against the horror that was to come; Joe was turning his back and pulling down his trousers even before the door was shut.

“Hold it right there, pal,” I said—but it was too late. I had no shotgun, and the cattle prod was on the blink.

“What do …