tbuckley/cabot-search huggingface dataset:
Home care in cystic fibrosis patients
Authors: WM van Aalderen, GP Mannes, ES Bosma, RJ Roorda, HS Heymans
Journal: European Respiratory Journal (1995)

Intravenous antibiotics and enteral tube feeding at home for the treatment of pulmonary exacerbations and underweight condition in cystic fibrosis (CF) patients have become tools that are used in many cystic fibrosis centres. The experience with home care programmes from different countries is quite conclusive. If the necessary preparations are made, such as training of staff and patients, and financial support is arranged, home care is easy to put into practice. Optimal patient compliance is also necessary. Home care is as effective as hospital treatment for selected patients, and less expensive. Experience has increased during many treatment periods in different cystic fibrosis centres, and only a few adverse events have been recorded, indicating that home care is safe. However, the most important gain for cystic fibrosis patients is the reduction of hospital admission time, which means a definite improvement in the quality of life.
Anti-alprenolol antibodies in the rabbit. A new probe for the study of beta-adrenergic receptor interaction.
Authors: S G Rockson, C J Homcy, E Haber
Journal: Circulation Research (1980)

We immunized rabbits with an antigen prepared by covalent linkage of alprenolol, a beta-adrenergic receptor antagonist, to bovine serum albumin. Competitive inhibition of [3H]dihydroalprenolol binding to antisera with a variety of unlabeled ligands revealed broad antibody specificity for beta-adrenergic antagonists and agonists. The antiserum was subjected to affintiy fractionation on hydroxybenzylpindolol-Sepharose 4B. Successive elution with 100 mM Tris HCl, 1M NaCl, 4 M LiBr, and 5 M guanidine yielded fractions with increasing affintiy for hydroxybenzylpindolol. The ligand-binding properties of these affinity-fractionated antibodies suggest that certain of these fractions recognize structural aspects of individual beta-adrenergic ligands which are irrelevant to their biological activity, whereas others can be used to distinguish shared functional properties, such as the ethanolamine side chain, within the structural heterogeneity of beta-adrenergic drugs. In particular, elution of hydroxybenzylpindolol-adsorbed antibody with (-)-propranolol allowed identification of an antibody fraction specific for the (-)-stereoisomer. Thus, affinity fractionation of antibodies raised against beta-adrenergic ligands can provide useful analogues for the further study of the recognition properties of the beta-adrenergic receptor.
Pancreatic Stellate Cells Radioprotect Pancreatic Cancer Cells through β1-Integrin Signaling
Authors: Tine S. Mantoni, Serena Lunardi, Osama Al-Assar, Atsushi Masamune, Thomas B. Brunner
Journal: Cancer Research (2011)

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a strong desmoplastic reaction where the stromal compartment often accounts for more than half of the tumor volume. Pancreatic stellate cells (PSC) are a central mediator of desmoplasia. There is increasing evidence that desmoplasia is contributing to the poor therapeutic response of PDAC. We show that PSCs promote radioprotection and stimulate proliferation in pancreatic cancer cells (PCC) in direct coculture. Our in vivo studies show PSC-dependent radioprotection in response to a single dose and to fractionated radiation. Abrogating β1-integrin signaling abolishes the PSC-mediated radioprotection in PCCs. Furthermore, this effect is independent of PI3K (phosphoinositide 3-kinase) but dependent on FAK. Taken together, we show for the first time that PSCs promote radioprotection of PCCs in a β1-integrin-dependent manner.
ErbB receptor regulation by dexamethasone in mouse type II epithelial cells
Authors: C. E. L. Dammann, N. Nassimi, W. Liu, H. C. Nielsen
Journal: European Respiratory Journal (2006)

Glucocorticoids stimulate foetal surfactant synthesis. Therefore, they are used in impending pre-term birth. One mechanism of action on surfactant synthesis is through the induction of neuregulin (NRG) secretion by foetal lung fibroblasts. The direct effects on signalling pathways, and specifically on erbB receptors in foetal type II cell surfactant synthesis, are less well understood. The present authors studied the effect of known promoters of foetal surfactant synthesis (namely dexamethasone and mature ( i.e. NRG-containing) fibroblast-conditioned medium (FCM)) on erbB receptor activation, protein content and dimerisation patterns in foetal mouse lung type II cells. Dexamethasone inhibited surfactant synthesis in immature type II cells at day (d)16 of gestation, while the mature FCM had stimulatory effects. Both treatments directly stimulated surfactant synthesis in more mature (d17) cells. At this gestational day, dexamethasone had only a small effect on phosphorylation, but it stimulated the protein levels of all four erbB receptors. Dexamethasone effects were distinct from those of mature FCM, which stimulated both protein content and phosphorylation of all erbB receptors and of the signalling intermediate phospholipase Cγ. Dexamethasone modulated erbB receptor dimerisation patterns, such that erbB2 became the main dimerisation partner for erbB4. In conclusion, dexamethasone signalling involves erbB receptors in foetal type II cells, in a manner similar to, but distinct from, neuregulin-containing fibroblast-conditioned medium signalling.
Leptin, body composition, and indices of malnutrition in patients on dialysis.
Authors: K L Johansen, K Mulligan, V Tai, M Schambelan
Journal: Journal of the American Society of Nephrology (1998)

A cross-sectional study was performed in a group of dialysis patients and control subjects to identify the determinants of serum levels of leptin, the protein product of the obese (ob) gene. Twenty-eight patients on dialysis (19 patients on hemodialysis [HD] and nine patients on peritoneal dialysis [PD]) and 41 healthy control subjects were studied. For each subject, blood was drawn for measurement of serum leptin levels and body composition was analyzed by dual-energy x-ray absorptiometry. Regression analyses were performed to determine the predictors of leptin levels, the independent contribution of HD and PD, and the relationship between leptin levels and markers of malnutrition and protein intake in the patients on dialysis. As expected, percentage of body fat was strongly correlated with leptin levels in the group as a whole and in each subgroup when analyzed separately. However, the slope of the relationship was significantly greater for dialysis patients than for control subjects (P < 0.05). Multivariate regression analysis showed that patients on HD and PD had higher leptin levels than control subjects even after adjustment for age, gender, and percentage of body fat. Univariate analyses were performed to assess the relationship between leptin levels and markers of nutritional status such as albumin, blood urea nitrogen, protein catabolic rate (PCR), transferrin, cholesterol, and lean body mass per height. There was a significant negative correlation between leptin levels and serum albumin (r = -0.598, P < 0.001) and between leptin and PCR (r = -0.433, P < 0.05) in the patients on dialysis. It is concluded that leptin levels adjusted for percentage of body fat are increased in dialysis patients compared with control subjects, particularly in those on PD. In addition, increased leptin levels are associated with low serum albumin levels and PCR in dialysis patients.
Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study
Authors: Mauro Moroni, Silvio Veronese, Silvia Benvenuti, Giovanna Marrapese, Andrea Sartore-Bianchi, Federica Di Nicolantonio, Marcello Gambacorta, Salvatore Siena, Alberto Bardelli
Journal: The Lancet Oncology (2005)
Inflammatory related changes in bone mineral content in adults with cystic fibrosis
Authors: C S Haworth
Journal: Thorax (2004)

<b>Background:</b> Proinflammatory cytokines stimulate osteoclast activity and this could lead to increased bone resorption in patients with cystic fibrosis. The aim of this study was to determine whether markers of systemic inflammation are related to changes in bone mineral content (BMC) in adults with cystic fibrosis. <b>Methods:</b> Total body BMC was assessed by dual energy <i>x </i>ray absorptiometry in 100 patients (54 male) of mean (SD) age 25.6 (7.1) years and forced expiratory volume in 1 second (FEV<sub>1</sub>) 61.8 (24.1)% predicted on recruitment to the study and 1 year later. Blood was also taken at these time points to measure markers of systemic inflammation. <b>Results:</b> After 1 year BMC had reduced by 16.1 (62.1) g, p = 0.01; (0.6 (2.8)%). The change in BMC was related to mean levels of interleukin (IL)-6 (<i>r</i><sub>s</sub> = −0.39, p&lt;0.001) and C reactive protein (<i>r</i><sub>s</sub> = −0.34, p = 0.002), intravenous antibiotic use (<i>r</i><sub>s</sub> = −0.27, p = 0.006) and oral corticosteroid use (<i>r</i><sub>s</sub> = −0.20, p = 0.045). Urinary markers of osteoclast activity were also related to IL-6 (<i>r</i><sub>s</sub> = 0.27, p = 0.02). Multiple linear regression revealed that IL-6 (coefficient –2.2 (95% CI –3.4 to –1.0) per pg/ml, p = 0.001), colonisation with <i>Burkholderia cepacia</i> (coefficient –46.8 (95% CI –75.5 to –18.1), p = 0.002), and annual change in BMI (coefficient 15.4 (95% CI 3.6 to 27.2) per kg/m<sup>2</sup>, p = 0.011) were independently significant predictors of annual change in BMC. <b>Conclusions:</b> These data suggest a pathophysiological mechanism by which chronic pulmonary infection results in bone loss in patients with cystic fibrosis.
The Ophthalmopathy of Graves' Disease
Authors: Judy A. Carter, Robert D. Utiger
Journal: Annual Review of Medicine (1992)

Ophthalmopathy is an integral component of Graves' disease. It usually appears at the same time as hyperthyroidism, and is characterized by proptosis (exophthalmos), periorbital and conjunctival edema, eye muscle dysfunction, and on occasion corneal ulceration or optic neuropathy. Graves' ophthalmopathy, like Graves' hyperthyroidism, is an autoimmune disease, but the mechanisms that initiate and maintain it are not known. Most patients can be treated conservatively, but a few require anti-inflammatory or surgical therapy to relieve symptoms and preserve vision.
Tumor cells escape suicide gene therapy by genetic and epigenetic instability
Authors: Oliver Frank, Cornelia Rudolph, Christoph Heberlein, Nils von Neuhoff, Evelin Schröck, Axel Schambach, Brigitte Schlegelberger, Boris Fehse, Wolfram Ostertag, Carol Stocking, Christopher Baum
Journal: Blood (2004)
Evolution of the Sweet Taste Receptor Gene Tas1r2 in Bats
Authors: H. Zhao, Y. Zhou, C. M. Pinto, P. Charles-Dominique, J. Galindo-Gonzalez, S. Zhang, J. Zhang
Journal: Molecular Biology and Evolution (2010)

Taste perception is an important component of an animal's fitness. The identification of vertebrate taste receptor genes in the last decade has enabled molecular genetic studies of the evolution of taste perception in the context of the ecology and dietary preferences of organisms. Although such analyses have been conducted in a number of species for bitter taste receptors, a similar analysis of sweet taste receptors is lacking. Here, we survey the sole sweet taste–specific receptor gene Tas1r2 in 42 bat species that represent all major lineages of the order Chiroptera, one of the most diverse groups of mammals in terms of diet. We found that Tas1r2 is under strong purifying selection in the majority of the bats studied, with no significant difference in the strength of the selection between insect eaters and fruit eaters. However, Tas1r2 is a pseudogene in all three vampire bat species and the functional relaxation likely started in their common ancestor, probably due to the exclusive feeding of vampire bats on blood and their reliance on infrared sensors rather than taste perception to locate blood sources. Our survey of available genome sequences, together with previous reports, revealed additional losses of Tas1r2 in horse, cat, chicken, zebra finch, and western clawed frog, indicating that sweet perception is not as conserved as previously thought. Nonetheless, we found no common dietary pattern among the Tas1r2-lacking vertebrates, suggesting different causes for the losses of Tas1r2 in different species. The complexity of the ecological factors that impact the evolution of Tas1r2 calls for a better understanding of the physiological roles of sweet perception in different species.
FURTHER STUDIES ON THE EFFECTS OF X-RADIATION ON THE MULTIPLICATION OF RICKETTSIA MOOSERI IN EMBRYONATE EGGS
Authors: Donald Greiff, E. L. Powers, Henry Pinkerton
Journal: The Journal of Experimental Medicine (1957)

The effect of x-rays on the growth of rickettsiae in the embryonate egg was investigated. The intensifying effect of x-radiation of the host on rickettsial growth can be attributed to alterations of the cells of the host that persist at least 7 days. The greatest enhancement of the growth of rickettsiae occurred when moderately infected cells were irradiated. These experiments indicate that x-rays may neutralize or reverse changes in the host that are unfavorable to the growth of rickettsiae. Explanations of the observed phenomena in terms of biochemical and biological alterations of the cells of the host are discussed.
Modulation of cardiac natriuretic peptide gene expression following endothelin type A receptor blockade in renovascular hypertension
Authors: L Bianciotti
Journal: Cardiovascular Research (2001)

Increased expression of the cardiac natriuretic peptides (NP), atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) is observed during chronic hemodynamic overload. The mechanisms underlying this process are not fully understood. In vitro, endothelin 1 (ET-1) is a powerful stimulator of cardiac NP and, therefore, has been assumed to be one possible mediator of increased NP gene expression following chronic pressure or volume overload. In the present work we investigated the possible role of ET-1 in mediating the observed upregulation of cardiac NP in two kidney-one clip (2K-1C) Goldblatt hypertensive rats treated for 6 weeks with the ET-1 type A (ET(A)) receptor subtype receptor antagonist ABT-627.2K-1C hypertension was induced in male Sprague-Dawley rats weighing 100-125 g by placing a silver clip (internal diameter 0.25 mm) around the left renal artery through a flank incision. The right kidney was left undisturbed. Sham operated rats underwent the same experimental procedures but no clip was placed on the left renal artery. ABT-627 was administered (10 mg/kg per day) in the drinking water for 6 weeks.In hypertensive rats, ABT-627 prevented a further rise in blood pressure beginning at 3 weeks after clipping and reduced the ventricular hypertrophy observed at the end of the experiment. ET(A) blockade prevented enhanced NP gene expression in the right ventricle and partially prevented it in the left ventricle. No modifications in atrial NP gene expression were observed in either control or 2K-1C animals. ET(A) blockade decreased BNP circulating levels but did not affect ANF plasma levels in clipped rats. ABT-627 increased alpha-myosin heavy chain gene expression and decreased the abundance of the beta isoform transcript.The results obtained in the present investigation show the participation of ET-1 in the increased expression of ventricular NP in 2K-1C renovascular hypertension and an apparent lack of effect of ET(A) blockade on atrial NP gene expression in both control and hypertensive animals thus showing that in vivo, atrial and ventricular NP gene expression are differentially regulated.
Nitrosative Stress in Rotated Three-Dimensional Colorectal Carcinoma Cell Cultures Induces Microtubule Depolymerization and Apoptosis
Authors: Luciana M. Laguinge, Shuling Lin, Raed N. Samara, Anastasios N. Salesiotis, J. Milburn Jessup
Journal: Cancer Research (2004)

Abstract Malignant cells undergo anoikis as they encounter fluid shear stress during transit to a metastatic site. We postulated that intracellular nitric oxide (NO) contributes to this cell death by comparing the growth of human colorectal carcinoma cells in low fluid shear stress rotated three-dimensional (Rotated 3-D) cultures with growth in static three-dimensional (Static 3-D) cultures on nonadherent surfaces and with two-dimensional monolayer (Monolayer 2-D) cultures. NO, loss of microtubules, and apoptosis increased significantly in Rotated 3-D cultures within 10 min and persisted at 24 h, whereas inhibition of NO synthase decreased apoptosis and intracellular NO and prevented tubulin degradation. Thus, fluid shear stress and three-dimensional growth increases NO synthase and NO to cause tubulin breakdown and induce anoikis. Intracellular NO in malignant cells entering the circulation may be a novel target for metastasis by colorectal carcinoma.
Oncostatin M, a Cytokine Released by Activated Mononuclear Cells, Induces Epithelial Cell-Myofibroblast Transdifferentiation via Jak/Stat Pathway Activation
Authors: Joanna Nightingale, Sharmila Patel, Naotaka Suzuki, Roger Buxton, Ken-ichro Takagi, Jun Suzuki, Yoshihiko Sumi, Atsushi Imaizumi, Roger M. Mason, Zhi Zhang
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Interactions between inflammatory infiltrates and resident tubular epithelial cells may play important roles in the development of tubulointerstitial fibrosis, by promoting epithelial cell-myofibroblast transdifferentiation (EMT). Human proximal tubular epithelial cells transdifferentiated to myofibroblasts after treatment with activated PBMC conditioned medium. mRNA and protein levels for α-smooth muscle actin, collagen I, and fibronectin EDA<sup>+</sup> (markers for the myofibroblastic phenotype) were increased, whereas those for E-cadherin and cytokeratin 19 (markers for the epithelial phenotype) were decreased. cDNA microarray analysis was used to identify other changes in gene expression that might point to novel molecular mechanisms driving EMT. Of 1176 array genes, 61 demonstrated at least a twofold change at at least two consecutive time points, of the five time points examined (0.5, 4, 8, 16, and 48 h). Of these genes, 59% were upregulated and 41% were downregulated. The array indicated upregulation of expression of the oncostatin M (OSM)-specific receptor β subunit from 4 to 48 h after exposure of kidney epithelial cells to activated PBMC conditioned medium, which contained high levels of OSM. In additional experiments, it was demonstrated that OSM induced EMT. OSM activated the Jak/Stat signaling pathway in epithelial cells, and a specific inhibitor of Jak2 blocked both its phosphorylation after exposure to OSM and the induction of α-actin and loss of cytokeratin 19 expression. Therefore, OSM is a novel inducer of EMT and is likely to be one of several cytokines produced by inflammatory infiltrates that contribute to this and subsequent tubulointerstitial fibrosis. E-mail: zzhang@tech.mrc.ac.uk
Inhomogeneity of ventricular refractory period in canine heart with quinidine-induced long QT interval: a comparative study on effects of heart rate, isoprenaline, and lignocaine
Authors: H. INOUE, I. TODA, A. NOZAKI, H. MATSUO, S. MASHIMA, T. SUGIMOTO
Journal: Cardiovascular Research (1985)

In anaesthetised open chest dogs, 30 mg·kg−1 of quinidine sulphate was injected intravenously over 5 min to produce QT prolongation. The sinus node was crushed. Effective refractory period (ERP) was determined at eight test points of the right ventricle using extra-stimuli after every seven basic ventricular pacings. Stimuli were of 2 ms duration and 1.5 times diastolic threshold. Temporal dispersion was estimated as the difference between the maximum and the minimum ERP of eight test points. Cycle lengths of basic ventricular drive were 700, 600, 500, and 400 ms. Time course of changes in ERP and its temporal dispersion was tested in five dogs. The effect of a 2 mg·kg−1 bolus injection followed by 70 μg·kg−1·min−1 drip infusion lignocaine, on quinidine-induced changes in ERP was studied in eight dogs, and that of a 0.06 μg·kg−1·min−1 infusion of isoprenaline, was tested in six dogs. ERP was significantly prolonged after quinidine injection (220 ± 20 vs 258 ± 25 ms n = 19, basic cycle length = 500 ms, p<0.001). Temporal dispersion was also increased after quinidine (18 ± 9 vs 33 ± 12 ms n = 19, basic cycle length = 500 ms, p<0.001). With shortening of basic cycle length (BCL), ERPs were shortened significantly. Temporal dispersion, however, did not change. Lignocaine prolonged ERP even further (250 ± 25 vs 273 ± 16 ms BCL = 500 ms, p<0.001). Although temporal dispersion tended to shorten during lignocaine infusion, the diference was not significant (31 ± 13 vs 23 ± 7, BCL = 500 ms). Isoprenaline significantly shortened both ERP and temporal dispersion (257 ± 27 vs 228 ± 28, p<0.001; 34 ± 6 vs 12 ± 4, p<0.01. BCL = 500 ms, respectively). This was also true for ERP and temporal dispersion of the earliest premature depolarisations. Results obtained in the present study might explain the underlying mechanisrn(s) of efficacy of cardiac pacing, lignocaine, and isoprenaline to suppress polymorphous ventricular tachycardia in clinical cases with quinidine-induced long QT interval.
Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial
Authors: Aimée HMM Arits, Klara Mosterd, Brigitte AB Essers, Eefje Spoorenberg, Anja Sommer, Michette JM De Rooij, Han PA van Pelt, Patricia JF Quaedvlieg, Gertruud AM Krekels, Pierre AFA van Neer, Joris J Rijzewijk, Adrienne J van Geest, Peter M Steijlen, Patty J Nelemans, Nicole WJ Kelleners-Smeets
Journal: The Lancet Oncology (2013)
Randomized, Placebo-Controlled Trial of Exposure and Ritual Prevention, Clomipramine, and Their Combination in the Treatment of Obsessive-Compulsive Disorder
Authors: Edna B. Foa, Michael R. Liebowitz, Michael J. Kozak, Sharon Davies, Rafael Campeas, Martin E. Franklin, Jonathan D. Huppert, Kevin Kjernisted, Vivienne Rowan, Andrew B. Schmidt, H. Blair Simpson, Xin Tu
Journal: American Journal of Psychiatry (2004)

The purpose of the study was to test the relative and combined efficacy of clomipramine and exposure and ritual prevention in the treatment of obsessive-compulsive disorder (OCD) in adults. Serotonin reuptake inhibitors (SRIs) and cognitive behavior therapy by exposure and ritual prevention are both established treatments for OCD, yet their relative and combined efficacy have not been demonstrated conclusively.A double-blind, randomized, placebo-controlled trial comparing exposure and ritual prevention, clomipramine, their combination (exposure and ritual prevention plus clomipramine), and pill placebo was conducted at one center expert in pharmacotherapy, another with expertise in exposure and ritual prevention, and a third with expertise in both modalities. Participants were adult outpatients (N=122 entrants) with OCD. Interventions included intensive exposure and ritual prevention for 4 weeks, followed by eight weekly maintenance sessions, and/or clomipramine administered for 12 weeks, with a maximum dose of 250 mg/day. The main outcome measures were the Yale-Brown Obsessive Compulsive Scale total score and response rates determined by the Clinical Global Impression improvement scale.At week 12, the effects of all active treatments were superior to placebo. The effect of exposure and ritual prevention did not differ from that of exposure and ritual prevention plus clomipramine, and both were superior to clomipramine only. Treated and completer response rates were, respectively, 62% and 86% for exposure and ritual prevention, 42% and 48% for clomipramine, 70% and 79% for exposure and ritual prevention plus clomipramine, and 8% and 10% for placebo.Clomipramine, exposure and ritual prevention, and their combination are all efficacious treatments for OCD. Intensive exposure and ritual prevention may be superior to clomipramine and, by implication, to monotherapy with the other SRIs.