tbuckley/cabot-search huggingface dataset:
Inhaled dry-powder formoterol and salmeterol in asthmatic patients: onset of action, duration of effect and potency
Authors: M Palmqvist, G Persson, L Lazer, J Rosenborg, P Larsson, J Lotvall
Journal: European Respiratory Journal (1997)

Salmeterol and formoterol are two long-acting beta2-agonists for inhalation, currently being used in clinical practice. The aim of the present study was to investigate the onset of action, duration of effect and potency of these two beta2-agonists in asthmatic patients. Patients (n=28) were included on the basis of salbutamol stepwise reversibility (100, 100 and 200 microg, given cumulatively; total reversibility > or =15%). In a double-blind placebo-controlled crossover study, the bronchodilating properties of formoterol 6, 12 and 24 microg were compared with the effects of salmeterol 50 microg. Formoterol was given via Turbuhaler and salmeterol via Diskhaler, and forced expiratory volume in one second (FEV1) was monitored during 12 h. Formoterol at all doses had a more rapid onset than salmeterol as judged from bronchodilation at 3 min after the dose. Formoterol at all doses had a similar duration of effect to salmeterol 50 microg, as judged from bronchodilation at 12 h after dose administration. When the relative potency of the two drugs was compared, salmeterol 50 microg was estimated to correspond to formoterol 9 microg (95% confidence interval: 3-19 microg). We confirm that formoterol and salmeterol are both long-acting beta2-agonists, but with some differences in effect profile. We confirm the more rapid onset of action of formoterol compared with salmeterol, and furthermore, no difference in duration of effect is evident.
Clinical Lecture on a Case of Strumous Ophthalmia, and on One of Sciatica
Authors: C. H. Jones
Journal: BMJ (1871)

but since subcutaneous injection was introduced this method is rarely employed.OBSERVATION OF EFFECTS.-After the drug has been administered, we allow the animal to move freely about, but prevent frogs from escap- ing by covering them with a large bell-jar.We then see whether the animal is restless or disinclined to move ; whether its movements are perfectly performed or unsteady; whether or not its legs seem weak and paralysed, or convulsive movements or involuntary twitchings be pre- sent; whether its heart-beats or pulse, and respirations, are quick or slow, strong or weakl; whether there is vomiting or purging diuresis; salivation; or dryness of the mouth; flow of tears, or dry conjunc- tiva; and whether the pupil be contracted or dilated.If the animal seem asleep, we pinch it to ascertain if reflex action continue after voluntary motion is gone ; and if respiration cease, we ascertain if the heart still continue to beat.As soon as possible after death, we open the animal and see if the heart still be beating.If it have stopped, we note whether its cavities are full or empty, its walls flaccid or firm,
The metastasis associated protein S100A4: a potential novel link to inflammation and consequent aggressive behaviour of rheumatoid arthritis synovial fibroblasts
Authors: L Oslejskova, M Grigorian, S Gay, M Neidhart, L Senolt
Journal: Annals of the Rheumatic Diseases (2007)

The metastasis-associated protein S100A4 belongs to the large family of S100 calcium-binding proteins that appear to play regulatory roles in diverse biological activities. Moreover, a prognostic role of S100A4 has been suggested for patients with several types of cancer. Cancer promoting properties for S100A4 have been demonstrated, particularly through its regulation of cell motility, proliferation and apoptosis, as well as by stimulation of angiogenesis and remodelling of the extracellular matrix. Increased expression of S100A4 mRNA has been detected in proliferating synovial fibroblasts in rheumatoid arthritis. Furthermore, strong upregulation of the S100A4 protein in rheumatoid arthritis synovial tissue compared with osteoarthritis and control tissues has been demonstrated recently, especially at sites of joint invasion. Several immune and vascular cells were also identified to be producing S100A4 within the synovium. The local upregulation of S100A4 was accompanied by high plasma and synovial fluid concentrations of the S100A4 protein existing in the bioactive oligomeric form in patients with rheumatoid arthritis. Consistent with data from cancer studies, the extracellular S100A4 oligomer appears to be involved in regulation of several matrix-degrading enzymes and modulation of the transcriptional activation function of the tumour suppressor protein p53 in rheumatoid arthritis synovial fibroblasts. Taken together, one can speculate that increased S100A4 protein in circulation and locally at sites of inflammation, particularly at sites of joint destruction, might be linked to the process of aggressive fibroblast behaviour contributing to the pathogenesis of chronic autoinflammatory diseases such as rheumatoid arthritis.
TGFbeta1 signaling via alphaVbeta6 integrin.
Authors: Martin P Kracklauer, Christian Schmidt, Guido M Sclabas
Journal: Molecular Cancer (2003)

Transforming growth factor β1 (TGFβ1) is a potent inhibitor of epithelial cell growth, thus playing an important role in tissue homeostasis. Most carcinoma cells exhibit a reduced sensitivity for TGFβ1 mediated growth inhibition, suggesting TGFβ1 participation in the development of these cancers. The tumor suppresor gene DPC4/SMAD4, which is frequently inactivated in carcinoma cells, has been described as a key player in TGFβ1 mediated growth inhibition. However, some carcinoma cells lacking functional SMAD4 are sensitive to TGFβ1 induced growth inhibition, thus requiring a SMAD4 independent TGFβ1 pathway. Here we report that mature TGFβ1 is a ligand for the integrin αVβ6, independent of the common integrin binding sequence motif RGD. After TGFβ1 binds to αVβ6 integrin, different signaling proteins are activated in TGFβ1-sensitive carcinoma cells, but not in cells that are insensitive to TGFβ1. Among others, interaction of TGFβ1 with the αVβ6 integrin resulted in an upregulation of the cell cycle inhibitors p21/WAF1 and p27 leading to growth inhibition in SMAD4 deleted as well as in SMAD4 wildtype carcinoma cells. Our data provide support for the existence of an alternate TGFβ1 signaling pathway that is independent of the known SMAD pathway. This alternate pathway involves αVβ6 integrin and the Ras/MAP kinase pathway and does not employ an RGD motif in TGFβ1-sensitive tumor cells. The combined action of these two pathways seems to be necessary to elicit a complete TGFβ1 signal.
How to write and publish a scientific paper
Authors: Clyde Williams
Journal: British Journal of Sports Medicine (1986)

emotional control.An examination of psychophysiological measures before and after stress inoculation training, together with well designed group experiments, would provide valuable information on the effect of the intervention and on the relationship between self-report and psychophysiological changes.It can be concluded, therefore, that while the present observations do not unequivocally establish stress inoculation as the instrument of change in this context, they give support to the view that it is a very useful technique for stress management in sport.
A switch in infected erythrocyte deformability at the maturation and blood circulation of Plasmodium falciparum transmission stages
Authors: Marta Tibúrcio, Makhtar Niang, Guillaume Deplaine, Sylvie Perrot, Emmanuel Bischoff, Papa Alioune Ndour, Francesco Silvestrini, Ayman Khattab, Geneviève Milon, Peter H. David, Max Hardeman, Kenneth D. Vernick, Robert W. Sauerwein, Peter R. Preiser, Odile Mercereau-Puijalon, Pierre Buffet, Pietro Alano, Catherine Lavazec
Journal: Blood (2012)
Herpes Simplex: Insights on Pathogenesis and Possible Vaccines
Authors: David M. Koelle, Lawrence Corey
Journal: Annual Review of Medicine (2008)

Abstract Herpes simplex viruses are evolutionarily ancient and ubiquitous. In the past 20 years, there has been increasing recognition of a worldwide pandemic of HSV-2 infection. Moreover, HSV-2 prevalence has increased despite fairly widespread use of antiviral drugs for HSV. The success of HSV-1 and HSV-2 stems from latency within long-lived neurons and frequent mucocutaneous shedding. The generally mild medical consequences of HSV infection reflect a functional equilibrium between host and microbe in most immunocompetent persons. However, significant gaps in our knowledge of the correlates of disease severity and HSV immune evasion are limiting rational advances in these areas. Human genetic studies are gradually outlining important innate responses, while recent imaging and biopsy studies have begun to show that the temporal and spatial anatomic interplay between virus reactivation and host immune response may be important in reactivations and disease expression.
Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat
Authors: Aaron M Cypess, Andrew P White, Cecile Vernochet, Tim J Schulz, Ruidan Xue, Christina A Sass, Tian Liang Huang, Carla Roberts-Toler, Lauren S Weiner, Cathy Sze, Aron T Chacko, Laura N Deschamps, Lindsay M Herder, Nathan Truchan, Allison L Glasgow, Ashley R Holman, Alina Gavrila, Per-Olof Hasselgren, Marcelo A Mori, Michael Molla, Yu-Hua Tseng
Journal: Nature Medicine (2013)
Immunochemotherapy with in vivo purging and autotransplant induces long clinical and molecular remission in advanced relapsed and refractory follicular lymphoma
Authors: L Arcaini, F Montanari, E P Alessandrino, A Tucci, E Brusamolino, L Gargantini, R Cairoli, P Bernasconi, F Passamonti, M Bonfichi, V Zoli, C Bottelli, S Calatroni, D Troletti, M Merli, C Pascutto, I Majolino, G Rossi, E Morra, M Lazzarino
Journal: Annals of Oncology (2008)
Even Superdoc can't fix patients' homes
Authors: L. S. Lewis
Journal: BMJ (2015)

McCartney is right again.1 Superdoc is the first port of call for any problem a patient may wish to present—it said so in the opening paragraph of “The Future General Practitioner” when I was a vocational training scheme trainee. But hey, hypothermic patients don’t normally complain, in my experience. The …
The novel small molecule drug Rabeximod is effective in reducing disease severity of mouse models of autoimmune disorders
Authors: M Hultqvist, K S Nandakumar, U Björklund, R Holmdahl
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: Autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS) affect a relatively large portion of the population, leading to severe disability if left untreated. Even though pharmaceutics targeting the immune system have revolutionised the therapy of these diseases, there is still a need for novel, more effective therapeutic substances. One such substance is the new chemical entity 9-chloro-2,3 dimethyl-6-( N , N -dimthylamino-2-oxoethyl)-6H-indolo [2,3-b] quionoxaline, Rabeximod, currently being investigated for efficiency in treatment of human RA. In this study we aimed to evaluate Rabeximod as a treatment for autoimmune diseases, using animal models. Methods: In the present investigation we have evaluated Rabeximod as a treatment for autoimmune diseases using mouse models of RA and MS, ie, collagen-induced arthritis, collagen antibody induced arthritis and experimental autoimmune encephalomyelitis. Results: Rabeximod efficiently prevented arthritis and encephalomyelitis in mice. In addition, this effect correlated to the timepoint when cells migrate into the joints. Conclusions: We conclude that Rabeximod reduces disease severity in animal models of autoimmunity and should be considered as a new therapeutic substance for MS and RA.
Incidence and short-term outcome of acute lung injury in mechanically ventilated children
Authors: P. Dahlem, W.M.C. van Aalderen, M.E. Hamaker, M.G.W. Dijkgraaf, A.P. Bos
Journal: European Respiratory Journal (2003)

The aim of this study was to determine the incidence and short-term outcome of mechanically ventilated children suffering from acute lung injury (ALI) on a paediatric intensive care unit (PICU). Between January 1 1998 and January 1 2000, all mechanically ventilated children were evaluated using the criteria of an American-European Consensus Conference. Of the 443 children eligible for analysis, 44 (9.9%) were diagnosed as suffering from ALI. Of these, 79.5% developed the acute respiratory distress syndrome (ARDS); 54.5% (24 of 44) fulfilled the ARDS criteria at inclusion and 25% (11 of 44) later. PICU mortality for ALI was 27.3% (12 of 44) and within the ARDS subgroup 31.4% (11 of 35). Of the 12 children who died, 11 had ARDS; the main cause of death was cerebral damage (seven of 12). Acute lung injury and acute respiratory distress syndrome are rare diseases on a paediatric intensive care unit with a high mortality. Most of the children with acute lung injury develop acute respiratory distress syndrome. In the acute respiratory distress syndrome subgroup, mortality is higher than in the acute lung injury nonacute respiratory distress syndrome subgroup. Further investigations should confirm prognostic factors (e.g. respiratory parameters) for prediction of outcome.
Heat shock protein 60 enhances CD4+ CD25+ regulatory T cell function via innate TLR2 signaling
Authors: A. Zanin-Zhorov
Journal: Journal of Clinical Investigation (2006)

CD4+CD25+ Tregs regulate immunity, but little is known about their own regulation. We now report that the human 60-kDa heat shock protein (HSP60) acts as a costimulator of human Tregs, both CD4+CD25int and CD4+CD25hi. Treatment of Tregs with HSP60, or its peptide p277, before anti-CD3 activation significantly enhanced the ability of relatively low concentrations of the Tregs to downregulate CD4+CD25– or CD8+ target T cells, detected as inhibition of target T cell proliferation and IFN-γ and TNF-α secretion. The enhancing effects of HSP60 costimulation on Tregs involved innate signaling via TLR2, led to activation of PKC, PI3K, and p38, and were further enhanced by inhibition of ERK. HSP60-treated Tregs suppressed target T cells both by cell-to-cell contact and by secretion of TGF-β and IL-10. In addition, the expression of ERK, NF-κB, and T-bet by downregulated target T cells was inhibited. Thus, HSP60, a self-molecule, can downregulate adaptive immune responses by upregulating Tregs innately through TLR2 signaling.
Cardiac-Directed Adenylyl Cyclase Expression Improves Heart Function in Murine Cardiomyopathy
Authors: David M. Roth, Mei Hua Gao, N. Chin Lai, Jeff Drumm, Nancy Dalton, Jin Yao Zhou, Jian Zhu, Daniel Entrikin, H. Kirk Hammond
Journal: Circulation (1999)

Background —We tested the hypothesis that increased cardiac myocyte adenylyl cyclase (AC) content increases cardiac function and response to catecholamines in cardiomyopathy. Methods and Results —Transgenic mice with cardiac-directed expression of AC type VI (AC VI ) were crossbred with mice with cardiomyopathy induced by cardiac-directed G q expression. G q mice had dilated left ventricles, reduced heart function, decreased cardiac responsiveness to catecholamine stimulation, and impaired β-adrenergic receptor (βAR)–dependent and AC-dependent cAMP production. G q /AC mice showed improved basal cardiac function in vivo ( P =0.01) and ex vivo ( P &lt;0.0005). When stimulated through the βAR, cardiac responsiveness was increased ( P =0.02), and cardiac myocytes showed increased cAMP production in response to isoproterenol ( P =0.03) and forskolin ( P &lt;0.0001). Conclusions —Increasing myocardial AC VI content in cardiomyopathy restores cAMP-generating capacity and improves cardiac function and responsiveness to βAR stimulation.
Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response
Authors: Birgit Liliensiek, Markus A. Weigand, Angelika Bierhaus, Werner Nicklas, Michael Kasper, Stefan Hofer, Jens Plachky, Herman-Josef Gröne, Florian C. Kurschus, Ann Marie Schmidt, Shi Du Yan, Eike Martin, Erwin Schleicher, David M. Stern, Günter J. Hämmerling, Peter P. Nawroth, Bernd Arnold
Journal: Journal of Clinical Investigation (2004)

While the initiation of the adaptive and innate immune response is well understood, less is known about cellular mechanisms propagating inflammation. The receptor for advanced glycation end products (RAGE), a transmembrane receptor of the immunoglobulin superfamily, leads to perpetuated cell activation. Using novel animal models with defective or tissue-specific RAGE expression, we show that in these animal models RAGE does not play a role in the adaptive immune response. However, deletion of RAGE provides protection from the lethal effects of septic shock caused by cecal ligation and puncture. Such protection is reversed by reconstitution of RAGE in endothelial and hematopoietic cells. These results indicate that the innate immune response is controlled by pattern-recognition receptors not only at the initiating steps but also at the phase of perpetuation.
Acute infective diarrhoea.
Authors: A. M. Ramsay
Journal: BMJ (1968)

Acute diarrhoea is produced by many infections, and labora tory investigations are essential for detection of the causal organisms. Nevertheless, despite careful search it is impossible in the majority of cases to isolate a bacterial pathogen or to demonstrate a virus to which there is an antibody response, though it is a fair assumption that bacteria or viruses are responsible and that the emergence of new techniques will enable us to identify them with greater accuracy. On the other hand, diarrhoea and vomiting may be the presenting feature in many conditions, notably infections of the urinary tract, pneu monia, meningitis, and septicaemia. In young children short epidemics in which there is a combination of acute respiratory and gastrointestinal upset are a by no means infrequent occur rence. Diarrhoea resulting from dietetic indiscretion must also be differentiated from diarrhoea of infective origin; this may sometimes be obvious from its transient nature and the absence of pyrexia and constitutional disturbance. In Britain chronic diarrhoea is seldom due to infection, and once giardiasis has been excluded investigation for ulcerative colitis, fibrocystic disease, coeliac disease, and genetic disorders of carbohydrate metabolism should be undertaken. There are certain well-defined groups of infective diarrhoeas which may be discussed separately.
Using PSA to Guide Timing of Androgen Deprivation in Patients with T0–4 N0–2 M0 Prostate Cancer not Suitable for Local Curative Treatment (EORTC 30891)
Authors: Urs E. Studer, Laurence Collette, Peter Whelan, Walter Albrecht, Jacques Casselman, Theo de Reijke, Hartmut Knönagel, Wolfgang Loidl, Santiago Isorna, Subramanian K. Sundaram, Muriel Debois
Journal: European Urology (2007)
Mongersen, an Oral <i>SMAD7</i> Antisense Oligonucleotide, and Crohn’s Disease
Authors: Giovanni Monteleone, Markus F. Neurath, Sandro Ardizzone, Antonio Di Sabatino, Massimo C. Fantini, Fabiana Castiglione, Maria L. Scribano, Alessandro Armuzzi, Flavio Caprioli, Giacomo C. Sturniolo, Francesca Rogai, Maurizio Vecchi, Raja Atreya, Fabrizio Bossa, Sara Onali, Maria Fichera, Gino R. Corazza, Livia Biancone, Vincenzo Savarino, Roberta Pica, Ambrogio Orlando, Francesco Pallone
Journal: New England Journal of Medicine (2015)

Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7.In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28.The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P=0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease.We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo. (Funded by Giuliani; EudraCT number, 2011-002640-27.).
Placental Steroid Hormone Biosynthesis in Primate Pregnancy*
Authors: EUGENE D. ALBRECHT, GERALD J. PEPE
Journal: Endocrine Reviews (1990)

Substantial advances in our understanding of placental function have resulted from recent establishment of in vitro approaches, such as cell culture, and application of molecular methods to study placental steroidogenesis. Insight into the processes of placental cell differentiation and hormonal function has been gained from culture of relatively pure preparations of cytotrophoblast. Various factors, e.g. cAMP and peptide growth factors, have been shown to have striking effects on progesterone and estrogen formation by placental tissue under in vitro conditions. Using advanced molecular approaches, the genes governing specific enzymes critical to placental steroidogenesis have been identified. Regulation of the mRNAs encoding specific enzyme peptides and thus expression of the genes by factors, such as cAMP, have been elucidated by Northern analysis and other techniques. It is critical that these contemporary approaches continue to be implemented aggressively to further elucidate placental function. However, it is clear from a survey of the literature, particularly of the past decade, that the vast majority of investigation in the area has been conducted in vitro. It is essential to determine whether the factors that have been observed to regulate placental endocrine function in vitro are operable in vivo. It is only with in vivo study that the dynamics of steroidogenesis and the complex functional relationships between placenta, fetus, and mother will be uncovered and understood. It is increasingly evident that the regulation of placental steroidogenesis involves autocrine and/or paracrine mechanisms, similar to those integral to hormone biosynthesis within other reproductive organs, e.g. ovary and testis. For example, as discussed above, estrogen regulates LDL uptake and P-450scc, and thus apparently is involved in generating substrate for progesterone production within the placenta. Conversely, progesterone has effects on 17 beta-hydroxysteroid oxidoreductase and thus the metabolism of estradiol, while androgens exert marked inhibitory effects on placental progesterone formation, at least in vitro. Not surprisingly, the regulation of placental progesterone and estrogen formation also is multifactorial. Thus, aromatase activity is stimulated synergistically by cAMP and phorbol esters, an effect that is suppressed by peptide growth factors. Therefore, the autocrine/paracrine and multifactorial regulation of hormone biosynthesis that has been relatively well documented in other tissues should be recognized as important in the primate placenta. Finally, the basic mechanisms underlying regulation of steroidogenesis within the fetoplacental unit during primate pregnancy appear similar, in important ways, to those of widely used laboratory animals, such as the rat and rabbit.(ABSTRACT TRUNCATED AT 400 WORDS)