tbuckley/cabot-search huggingface dataset:
β1 integrin mediates toll-like receptor 2 induced migration and invasion via rac1 activation
Authors: T McGarry, M Connolly, J McCormick, W Gao, D J Veale, U Fearon
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by synovial inflammation and destruction of cartilage and bone. TLR-2 is implicated in the pathogenesis of RA. This study investigates if TLR-2 induced cell migration and invasion is mediated through β1-integrin signalling pathways and cytoskeletal dynamics. <h3>Materials and methods</h3> IA patients (n=20) underwent clinical assessment, video-arthroscopy and synovial biopsy pre/postbiologic therapy. Macroscopic synovitis/vascularity was measured by visual analogue scale.Immunohistology/immunoflourescence examined β1 integrin and filamentous actin (F-actin) expression in synovial tissue (ST), primary RA synovial fibroblasts (RASFC) and microvascular endothelial cells (MVEC). Cytoskeletal rearrangement following Pam3CSK4 (1ug/ml) (TLR-2-ligand) stimulation was examined by F-actin immunofluorescent staining. Pam3CSK4 induced adhesion, cell migration and invasion was assessed by FACS analysis, wound repair assays and transwell matrigel invasion chambers in the presence or absence of anti-β1 integrin (10 µg/ml) or IgG control antibody (10 µg/ml). Rac1 was assessed by immunoprecipitation and western blotting. <h3>Results</h3> β1 integrin was highly expressed in IA ST compared to osteoarthritis and control tissue. β1 integrin lining and sublining layer expression significantly correlated with macroscopic synovitis (p&lt;0.05), vascularity (p&lt;0.05), and was significantly reduced in biologic responders. β1-integrin and F-actin expression predominantly co-localised to synovial blood vessels and lining layer. Pam3CSK4 induced cell surface expression of ICAM (p&lt;0.05). Using RASFC and HDEC, Pam3CSK4 induced cell migration and cytoskeletal disassembly, resulting in filopodia and microspike formation and significantly induced Rac1 activation and cell invasion through a matrigel (p&lt;0.05). Finally, the authors demonstrated that Pam3CSK4 induced cell migration was inhibited in the presence of anti- β1 integrin, an effect that was also observed for Pam3CSK4 induced cellular invasion and Rac1 activation (p&lt;0.05). No effect was observed for IgG matched control antibody. <h3>Conclusion</h3> β1-integrin is highly expressed in the inflamed joint and mediates cell TLR-2 induced migrational and invasive mechanisms, critical to the pathogenesis of IA.
Increased Noise Level of Purkinje Cell Activities Minimizes Impact of Their Modulation during Sensorimotor Control
Authors: F.E. Hoebeek, J.S. Stahl, A.M. van Alphen, M. Schonewille, C. Luo, M. Rutteman, A.M.J.M. van den Maagdenberg, P.C. Molenaar, H.H.L.M. Goossens, M.A. Frens, C.I. De Zeeuw
Journal: Neuron (2005)
Effects of skin occlusion in patch testing with sodium lauryl sulphate
Authors: K. Friebe, I. Effendy, H. Loffler
Journal: British Journal of Dermatology (2003)

When evaluating transepidermal water loss (TEWL) in patch testing, the occlusive effect of the patch must be considered as an important artificial impairment of the measurement.To investigate the time course of effects of occlusion.Epicutaneous patches with sodium lauryl sulphate (SLS) 0.25%, SLS 0.5%, water and an empty test chamber (control) were applied on the volar forearm for different time intervals (12, 24, 48 h). Test reactions were evaluated by measurement of TEWL immediately, every 15 min during the first hour, every 30 min during the following 3 h and 24 h after patch removal.After patch removal, TEWL values showed a steep increase. When compared with basal values, TEWL values after SLS patch testing remained increased for 24 h, whereas TEWL values on water patch sites were only significantly increased for up to 180 min, and on empty patch sites for only up to 120 min after patch removal. The prolonged increase in TEWL values in SLS patch testing seemed to be induced by barrier function damage caused by SLS itself, as shown in various earlier studies. After the initial increase, TEWL values showed a significant decrease for all patches from 0 to 120 min after patch removal. Patch testing with water gave a significant decrease in TEWL values up to 180 min, and for empty chambers (control) up to 150 min after removal of patches. These data suggest that the occlusive effect on TEWL in patch testing ends 3 h after the removal of test chambers.We recommend TEWL measurement in SLS patch testing after a period of at least 3 h after patch removal. For practical purposes a 24-h period after patch removal may be useful.
Cinacalcet HCl, an Oral Calcimimetic Agent for the Treatment of Secondary Hyperparathyroidism in Hemodialysis and Peritoneal Dialysis
Authors: Jill S. Lindberg, Bruce Culleton, Gordon Wong, Michael F. Borah, Roderick V. Clark, Warren B. Shapiro, Simon D. Roger, Fred E. Husserl, Preston S. Klassen, Matthew D. Guo, Moetaz B. Albizem, Jack W. Coburn
Journal: Journal of the American Society of Nephrology (2005)

Management of secondary hyperparathyroidism is challenging with traditional therapy. The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium, thereby reducing parathyroid hormone (PTH) secretion. This phase 3, multicenter, randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis (HD) and peritoneal dialysis (PD) patients with PTH ≥300 pg/ml despite traditional therapy. A total of 395 patients received once-daily oral cinacalcet (260 HD, 34 PD) or placebo (89 HD, 12 PD) titrated from 30 to 180 mg to achieve a target intact PTH (iPTH) level of ≤250 pg/ml. During a 10-wk efficacy assessment phase, cinacalcet was more effective than control for PTH reduction outcomes, including proportion of patients with mean iPTH levels ≤300 pg/ml (46 <i>versus</i> 9%), proportion of patients with ≥30% reduction in iPTH from baseline (65 <i>versus</i> 13%), and proportion of patients with ≥20, ≥40, or ≥50% reduction from baseline. Cinacalcet had comparable efficacy in HD and PD patients; 50% of PD patients achieved a mean iPTH ≤300 pg/ml. Cinacalcet also significantly reduced serum calcium, phosphorus, and Ca × P levels compared with control treatment. The most common side effects, nausea and vomiting, were usually mild to moderate in severity and transient. Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH, Ca × P, calcium, and phosphorus levels in patients who received HD or PD. Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.
Neurological complications of enteric disease.
Authors: A Wills, C J Hovell
Journal: Gut (1996)

Leading article Neurological complications of enteric diseaseNeurological complications can arise as complications in up to 10% of patients with chronic enteric diseases.The underlying mechanisms may in time offer insights into the pathogenesis of gastrointestinal diseases.This article reviews the complications of adult enteric disease and summarises current theories of pathogenesis.Crohn's disease Crohn's disease (CD) is an idiopathic intestinal disorder of unknown cause.'In contrast with ulcerative colitis, inflam-
Spinal Injection Therapy for Low Back Pain
Authors: J. Bart Staal, Patty J. Nelemans, Rob A. de Bie
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
[177Lu]Pertuzumab: Experimental Therapy of HER-2–Expressing Xenografts
Authors: Mikael Persson, Lars Gedda, Hans Lundqvist, Vladimir Tolmachev, Hans Nordgren, Per-Uno Malmström, Jörgen Carlsson
Journal: Cancer Research (2007)

Abstract Pertuzumab (Omnitarg) is a novel antibody against HER-2, domain II. HER-2 is a tyrosine kinase receptor that is overexpressed in several carcinomas, especially breast cancer. Pertuzumab, labeled with the low-energy β emitter 177Lu, might be a candidate for targeted radiotherapy of disseminated HER-2–positive micrometastases. The radiolabeled antibody [177Lu]pertuzumab showed favorable targeting properties in BALB/c (nu/nu) mice with HER-2–overexpressing xenografts. The absorbed dose in tumors was more than five times higher than the absorbed dose in blood and more than seven times the absorbed dose in any other normal organ. Experimental therapy showed that [177Lu]pertuzumab delayed tumor progression compared with controls (no treatment, P &amp;lt; 0.0001; nonlabeled pertuzumab antibody, P &amp;lt; 0.0001; and 177Lu-labeled irrelevant antibody, P &amp;lt; 0.01). No adverse side effects of the treatment could be detected. Thus, the experimental results support the planning of clinical studies applying [177Lu]pertuzumab for therapy. [Cancer Res 2007;67(1):326–31]
A double-blind randomized trial of nicotine nasal spray as an aid in smoking cessation
Authors: T Blondal, M Franzon, A Westin
Journal: European Respiratory Journal (1997)

The objective of the study was to evaluate the therapeutic efficacy of nicotine nasal solution (NNS) for smoking cessation from the stopping day up to 3 months. We also followed the participants for 2 yrs after ceasing smoking to assess what happens after stopping using NNS. In a placebo-controlled, double-blind, 2 yr prospective study, 157 smokers were given either NNS, one dose containing 1 mg of nicotine per 100 microL (n=79), or placebo (n=78). Treatment was continued for up to 1 yr. One day after quitting smoking, the average number of daily doses was 11 in the group assigned NNS and 14 in the group assigned the placebo, and after 6 weeks, 14 and 6 doses, respectively, among abstinent participants still using spray. After 3 months, 65% of the abstainers in the nicotine group were still using the NNS. The abstinence rates were 51, 39 and 29% after 6 weeks, 3 and 6 months, respectively, as compared to 24, 19 and 18% in the placebo group (p=0.0003; p=0.003; p=0.050). The proportion abstinent at the 1 yr (25 vs 17%) and 2 yr follow-ups (19 vs 14%) was higher among those assigned to the nicotine than to the placebo group, but not significantly so for the numbers used in the study. In conclusion, the use of nicotine nasal spray significantly increased the abstinence rate during the first 6 months following the quitting day.
Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections
Authors: Sherry R. Crowe, Stephen J. Turner, Shannon C. Miller, Alan D. Roberts, Rachel A. Rappolo, Peter C. Doherty, Kenneth H. Ely, David L. Woodland
Journal: The Journal of Experimental Medicine (2003)

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies.
Association between domestic mould and mould components, and asthma and allergy in children: a systematic review
Authors: C. Tischer, C-M. Chen, J. Heinrich
Journal: European Respiratory Journal (2011)

Critical reviews over the past 10 yrs have found increased respiratory and allergic health outcomes for children living in damp and mouldy environments. However, recent studies have suggested that early childhood exposure to specific mould components may actually protect children from developing allergy. We conducted a systematic review of observational studies published in English from January 1980 to July 2010. This review was conducted according to systematic guidelines for Meta-analyses of Observational Studies in Epidemiology (MOOSE). The literature was searched using a computerised bibliographic database, PubMed. In order to increase the quality of the reviewed studies, meta-analyses of the effects of visible mould exposure on allergic health outcomes were performed and we evaluated the findings according to the Bradford Hill criteria for evidence of causation. The literature search identified 1,398 peer-reviewed scientific publications, and 61 studies that fulfilled the inclusion criteria were included in this review. We observed increased risks of allergic respiratory health outcomes in children exposed to visible mould and mould spores. These findings were confirmed by the results of the meta-analysis and in line with the evaluation criteria according to Bradford Hill. Visible mould was positively associated with asthma (OR 1.49 (95% CI 1.28–1.72)), wheeze (OR 1.68 (95% CI 1.48–1.90)) and allergic rhinitis (OR 1.39 (95% CI 1.28–1.51)). However, there was a tendency of lower risk for allergic health outcomes in children exposed to mould-derived components such as (1,3)-β- d -glucan and extracellular polysaccharides. These findings suggest that home environments with visible mould and mould spore exposure increase the risk of allergic respiratory health outcomes in children. However, further investigations are needed to examine the effects of exposure to mould-derived components as the current literature is inconclusive. In order to disentangle the different effects of overall microbial exposure on children’s health, research should focus on specific microbial markers in the home, in combination with new assessment techniques including molecular methods.
Airway hyperresponsiveness to histamine associated with accelerated decline in FEV1.
Authors: B Rijcken, J P Schouten, X Xu, B Rosner, S T Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

An increased level of airway responsiveness has been proposed as a risk factor associated with the onset and prognosis of chronic airway obstruction. To determine this, longitudinal studies are necessary, with measurement of both the level of airway responsiveness and of additional risk factors, such as cigarette smoking, made before measurement of pulmonary function decline. The association of airways responsiveness with decline in FEV1 has been prospectively studied in a random sample of the Dutch population. Longitudinal data from 921 males, providing 2,376 paired observations, and 698 females, providing 1,682 paired observations, were used for analysis. Differences between responders and nonresponders (PC10 < or = 16 mg/ml of histamine) were estimated from linear regression analyses stratified by gender and smoking status, with adjustment for age, residential area, the presence of respiratory symptoms, indicators for each interval, and residuals of FEV1 at the beginning of the interval. Responders had a greater mean yearly decline in FEV1, and the differences between responders and nonresponders were similar for all gender and smoking subgroups. In an overall regression model, subjects with airway hyperresponsiveness had a significantly steeper decline in FEV1, independent of the other variables (males: beta = -12.5 ml/yr, SEM = 3.22, p < 0.001; females: beta = -11.50 ml/yr, SEM = 2.98, p < 0.001). The current analyses conclusively demonstrated that increased airway responsiveness is an independent risk factor for an accelerated decline in FEV1 and, hence, for the development of chronic obstructive lung disease. The mechanisms by which increased airway responsiveness leads to an accelerated decline in FEV, are imperfectly understood and require further study.
Synthesis of Phospholipid by Foam Cells Isolated from Rabbit Atherosclerotic Lesions
Authors: ALLEN J. DAY, H. A. I. NEWMAN, D. B. ZILVERSMIT
Journal: Circulation Research (1966)

In a preliminary study, foam cells from atherosclerotic lesions have been isolated by incubation of the intima with collagenase and elastase. The composition and metabolism of homogeneous preparations of foam cells obtained in this way have been compared with other parts of the atherosclerotic intima. About 1% of the cholesterol and phospholipid of the intima was present in the cells obtained. The phospholipids of the foam cells contained a lower percentage of lecithin and of sphingomyelin and a higher percentage of "phosphatidyl ethanolamine" than the other parts of the intima. The isolated foam cells incubated in vitro incorporated P 32 -phosphate into phospholipid at a rate of about 0.5 mµmoles/10 6 cells/hr. The P 32 was incorporated mainly into lecithin and phosphatidyl inositol with smaller amounts incorporated into phosphatidyl ethanolamine, sphingomyelin and lysolecithin. The amount of P 32 incorporated into phospholipid by the foam cells was compared with that incorporated into phospholipid by other portions of the intima when the aorta was incubated in vitro prior to disruption. Up to 6.8% of the phospholipid synthesis was brought about by isolated cells. The significance of the findings in relation to phospholipid synthesis in the atherosclerotic lesion was discussed.
Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505
Authors: Ryo Kitagawa, Noriyuki Katsumata, Taro Shibata, Toshiharu Kamura, Takahiro Kasamatsu, Toru Nakanishi, Sadako Nishimura, Kimio Ushijima, Masashi Takano, Toyomi Satoh, Hiroyuki Yoshikawa
Journal: Journal of Clinical Oncology (2015)

Purpose In metastatic or recurrent cervical cancer, cisplatin-based chemotherapy is standard. The JCOG0505 randomized phase III trial evaluated the clinical benefits of carboplatin-based regimen. Patients and Methods Eligible patients had metastatic or recurrent cervical cancer and had ≤ one platinum-containing treatment and no prior taxane. Patients were randomly assigned either to conventional paclitaxel plus cisplatin (TP; paclitaxel 135 mg/m 2 over 24 hours on day 1 and cisplatin 50 mg/m 2 on day 2, repeated every 3 weeks) or paclitaxel plus carboplatin (TC; paclitaxel 175 mg/m 2 over 3 hours and carboplatin area under curve 5 mg/mL/min on day 1, repeated every 3 weeks). Primary end point was overall survival (OS). Planned sample size was 250 patients to confirm the noninferiority of TC versus TP with the threshold hazard ratio (HR) of 1.29. Results Between February 2006 and November 2009, 253 patients were enrolled. The HR of OS was 0.994 (90% CI, 0.79 to 1.25; noninferiority P = .032 by stratified Cox regression). Median OS was 18.3 months with TP versus 17.5 months with TC. Among patients who had not received prior cisplatin, OS was shorter with TC (13.0 v 23.2 months; HR, 1.571; 95% CI, 1.06 to 2.32). One treatment-related death occurred with TC. Proportion of nonhospitalization periods was significantly longer with TC (P &lt; .001). Conclusion TC was noninferior to TP and should be a standard treatment option for metastatic or recurrent cervical cancer. However, cisplatin is still the key drug for patients who have not received platinum agents.
Podocyte Number in Children and Adults
Authors: Victor G. Puelles, Rebecca N. Douglas-Denton, Luise A. Cullen-McEwen, Jinhua Li, Michael D. Hughson, Wendy E. Hoy, Peter G. Kerr, John F. Bertram
Journal: Journal of the American Society of Nephrology (2015)

Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define baseline values of early life and 12 adults (≥18 years old), were collected at autopsy in Jackson, Mississippi. We used a combination of immunohistochemistry, confocal microscopy, and design-based stereology to estimate individual glomerular volume (IGV) and numbers of podocytes, nonepithelial cells (NECs; tuft cells other than podocytes), and parietal epithelial cells (PECs). Podocyte density was calculated. Data are reported as medians and interquartile ranges (IQRs). Glomeruli from children were small and contained 452 podocytes (IQR=335–502), 389 NECs (IQR=265–498), and 146 PECs (IQR=111–206). Adult glomeruli contained significantly more cells than glomeruli from children, including 558 podocytes (IQR=431–746; P<0.01), 1383 NECs (IQR=998–2042; P<0.001), and 367 PECs (IQR=309–673; P<0.001). However, large adult glomeruli showed markedly lower podocyte density (183 podocytes per 106µm3) than small glomeruli from adults and children (932 podocytes per 106µm3; P<0.001). In conclusion, large adult glomeruli contained more podocytes than small glomeruli from children and adults, raising questions about the origin of these podocytes. The increased number of podocytes in large glomeruli does not match the increase in glomerular size observed in adults, resulting in relative podocyte depletion. This may render hypertrophic glomeruli susceptible to pathology.
Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE
Authors: Laura Bouchareychas, John Pirault, Flora Saint-Charles, Virginie Deswaerte, Tiphaine Le Roy, Wendy Jessup, Philippe Giral, Wilfried Le Goff, Thierry Huby, Emmanuel L. Gautier, Philippe Lesnik
Journal: Cardiovascular Research (2015)

AimsMacrophage apoptosis is a prominent feature of atherosclerosis, yet whether cell death-protected macrophages would favour the resolution of already established atherosclerotic lesions, and thus hold therapeutic potential, remains unknown.