tbuckley/cabot-search huggingface dataset:
Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor and low-density lipoprotein on proliferation and migration of keratinocytes
Authors: M.I.A. Abd El-Latif, H. Murota, M. Terao, I. Katayama
Journal: British Journal of Dermatology (2010)

Keratinocytes can obtain cholesterol either by de novo synthesis or by extraction, primarily from low-density lipoprotein (LDL). LDL is internalized following binding to the LDL receptor (LDLR). Because LDLR is expressed at a higher level in the cells of the basal layer of the epidermis, it might be assumed that LDLR upregulation is associated with keratinocyte proliferation. However, the effect of LDLR stimulation on keratinocyte function remains unclear.To investigate the effects and mechanism of action of pitavastatin and effects of LDL on proliferation and migration of keratinocytes.Pitavastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was used to induce upregulation of LDLR. LDLR expression was evaluated by immunofluorescence staining, fluorescence-activated cell sorting, immunohistochemical staining and real-time polymerase chain reaction (PCR). HaCaT cells and normal human keratinocytes (NHKs) were used for evaluation of migration. 5-Bromo-2'-deoxyuridine incorporation was used to evaluate keratinocyte proliferation and differentiation. C57BL6 mice were used for in vivo evaluation of the effect of topical pitavastatin or lovastatin.Pitavastatin was most effective in LDLR induction at a concentration of 1 micromol L(-1) in NHKs. Real-time PCR showed that pitavastatin significantly increased LDLR and liver X receptor (LXR) beta mRNA expression in these cells. Similar results were obtained in vivo. However, pitavastatin had no effect on the migration of NHKs. After the addition of LDL and/or mevalonate concomitantly with pitavastatin to NHK cultures, or topical application of pitavastatin on mouse skin, keratinocyte proliferation was significantly increased.Pitavastatin significantly upregulates LDLR in both NHKs and C57BL6 mouse skin, resulting in increased keratinocyte proliferation. LXRbeta may be involved in the pitavastatin-induced keratinocyte proliferation.
Zoledronic Acid and Angiogenesis
Authors: Daniele Santini, Bruno Vincenzi, Giuseppe Tonini
Journal: Clinical Cancer Research (2007)

In Response: We read with interest the reply by Ferretti and colleagues to our recent article in Clinical Cancer Research ([1][1]). We show appreciation to the authors for further emphasizing that fractioned and intermittent administration of bisphosphonates represents a new potential therapy
Efficacy of cyclo-oxygenase-2 inhibition by etoricoxib and naproxen on the axial manifestations of ankylosing spondylitis in the presence of peripheral arthritis
Authors: L Gossec
Journal: Annals of the Rheumatic Diseases (2005)

The combined efficacy of selective and non-selective cyclo-oxygenase-2 (COX-2) inhibition on the axial manifestations of ankylosing spondylitis (AS) in the presence or absence of chronic peripheral arthritis was evaluated.In a post hoc subgroup analysis of a 6 week, randomised, double blind, placebo controlled trial, 387 patients with active axial AS were randomised to receive etoricoxib 90 mg or 120 mg once a day, naproxen 500 mg twice daily, or placebo. Randomisation was stratified by the presence or absence of chronic peripheral arthritis. The primary outcome measure was the time weighted average change from baseline of spine pain intensity. Efficacy data from the three groups receiving active treatment (the NSAID/COX-2 inhibitor group) were combined to improve precision. An analysis of covariance model was used to evaluate the effect of peripheral disease on treatment response.93 patients were allocated to receive placebo and 294 to active treatment (naproxen or etoricoxib). The combined NSAID/COX-2 inhibitor group had a significant treatment response compared with the placebo group for all efficacy measures, both in patients with and without peripheral arthritis. A significantly greater difference in mean patient assessment of spine pain was found between active and placebo treatments in patients without compared with those with peripheral arthritis (p = 0.005; -32.5 mm v -17.0 mm, respectively). Similar differences, although not statistically significant, were seen for other end points.NSAIDs and COX-2 inhibitors have a clinically relevant symptomatic effect on axial AS irrespective of the presence of peripheral arthritis. In this exploratory analysis spinal improvement appeared to be greater in patients without peripheral disease.
Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease)
Authors: Godfrina McKoy, Nikos Protonotarios, Andrew Crosby, Adalena Tsatsopoulou, Aris Anastasakis, Aman Coonar, Mark Norman, Christina Baboonian, Steve Jeffery, William J McKenna
Journal: The Lancet (2000)
Presidential Address ON THE RISE AND PROGRESS OF LARYNGOLOGY: ITS RELATION TO GENERAL MEDICINE AND ITS POSITION IN THE MEDICAL CURRICULUM: Delivered before the Manchester Medical Society
Authors: W. Milligan
Journal: BMJ (1922)

SPECIALISM in medicine or surgery is no new-fangled idea.Herodotus, the Father of History, writing more than 2,500 years ago of the highly developed state of specialism amongst the Egyptians, says: "Physicke is so studied and practised with the Egyptians that every disease has its several phvsician wlio striveth to excel ifi healing that one disease and not to be expert in curing many.Whereof it cometh that every corner of that Country is full of physicians, some for the eyes, others for the head, many for the teeth, and not a few for the stomach and the inwards."In those far-off days the human body was divided into some thirtyy-six regions, with specialists-for each one of them,
Incidence of Diabetes in Children and Youth—Tracking a Moving Target
Authors: Rebecca B. Lipton
Journal: JAMA (2007)

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
Early Insulin Treatment in Type 2 Diabetes
Authors: Luigi F. Meneghini
Journal: Diabetes Care (2009)

The prevalence of diabetes in the world is growing at an unprecedented rate and rapidly becoming a health concern and burden in both developed and developing countries (1). In addition, we are now witnessing an upsurge in the incidence of type 2 diabetes in children and adolescents, with the potential of translating into a future catastrophic disease burden as vascular complications of the disease begin affecting a younger population. Although there may be contention regarding the impact of lowering glycemia on macrovascular disease risk, there is strong consensus of the definite benefits of lowering blood glucose to reduce the risk of retinopathy and nephropathy in either type 1 or type 2 diabetes (2,3). Despite supporting data and multiple guidelines advanced by professional organizations, overall glycemic control falls far below expectations (4). Overall, <36% of individuals with diabetes are at recommended glycemic targets, with the most difficult-to-control cases represented by insulin-deficient individuals on insulin therapy to manage their diabetes (4). Furthermore, as β-cell dysfunction progresses over time, many patients with type 2 diabetes, treated with oral agents, fail to achieve or maintain adequate glycemic control. Unfortunately, in many of these cases, antiglycemic therapy is not adjusted or advanced, thereby exposing patients to prolonged hyperglycemia and the increased risk of diabetes-related complications. The term “clinical inertia,” which has come to define the lack of initiation, or intensification of therapy when clinically indicated (5), is most pronounced in the setting of insulin initiation. Subjects with type 2 diabetes, managed in a large integrated health care system, were initiated on additional blood glucose–lowering treatment only when the mean baseline A1C reached a value of 9.0% (6). Patients started on insulin had an even higher mean A1C of 9.6% and tended to have more severe baseline complications and comorbidities than those started on …
Distinct roles for the NF-κB1 and c-Rel transcription factors in the differentiation and survival of plasmacytoid and conventional dendritic cells activated by TLR-9 signals
Authors: Meredith O'Keeffe, Raelene J. Grumont, Hubertus Hochrein, Martina Fuchsberger, Raffi Gugasyan, David Vremec, Ken Shortman, Steve Gerondakis
Journal: Blood (2005)
Sézary syndrome associated with granulomatous lesions during treatment with bexarotene
Authors: A. Ruiz-de-Casas, A. Carrizosa-Esquivel, A. Herrera-Saval, J. J. Rios-Martín, F. Camacho
Journal: British Journal of Dermatology (2005)

Journal Article Sézary syndrome associated with granulomatous lesions during treatment with bexarotene Get access A. Ruiz‐de‐Casas, A. Ruiz‐de‐Casas Departments of Dermatology and Pathology, Virgen Macarena University Hospital, Seville, Spain Dr Andrés Ruiz‐de‐Casas. E‐mail: aruizdecasas@aedv.es Search for other works by this author on: Oxford Academic Google Scholar A. Carrizosa‐Esquivel, A. Carrizosa‐Esquivel Departments of Dermatology and Pathology, Virgen Macarena University Hospital, Seville, Spain Search for other works by this author on: Oxford Academic Google Scholar A. Herrera‐Saval, A. Herrera‐Saval Departments of Dermatology and Pathology, Virgen Macarena University Hospital, Seville, Spain Search for other works by this author on: Oxford Academic Google Scholar J. J. Rios‐Martín, J. J. Rios‐Martín Departments of Dermatology and Pathology, Virgen Macarena University Hospital, Seville, Spain Search for other works by this author on: Oxford Academic Google Scholar F. Camacho F. Camacho Departments of Dermatology and Pathology, Virgen Macarena University Hospital, Seville, Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 2, 1 February 2006, Pages 372–374, https://doi.org/10.1111/j.1365-2133.2005.07034.x Published: 01 February 2006 Article history Accepted: 09 June 2005 Published: 01 February 2006
Scintigraphic comparison of budesonide deposition from two dry powder inhalers
Authors: S.P. Newman, G.R. Pitcairn, P.H. Hirst, R.E. Bacon, E. O'Keefe, M Reiners, R Hermann
Journal: European Respiratory Journal (2000)

Chlorofluorocarbons (CFCs), used in metered dose inhalers (MDIs), have been identified as being deleterious to the environment leading to a ban on their production. Dry powder inhalers (DPIs) are a widely used alternative to MDIs. One disadvantage of DPIs is that in vivo lung deposition can be influenced by the patient9s inspiratory flow rate. The ASTA Medica multi-dose dry powder inhaler (AM-MDPI) has been designed to offer low resistance on inhalation, so that asthmatic patients can achieve inhaled flow rates of approximately 90 L x min(-1). The aim of the study was to evaluate the in vivo deposition of budesonide from the AM-MDPI at different flow rates and to compare this with delivery from a Turbuhaler DPI at a high flow rate. The study was a scintigraphic, randomized, crossover study in which 13 healthy volunteers inhaled a single 200 microg dose of radiolabelled budesonide on four separate occasions with a minimum 44-h washout period between dosings. At the lowest flow rate of 54 L x min(-1), comparable to that for the Turbuhaler (58 L x min(-1)), a similar percentage of the metered dose was delivered to the lung (AM-MDPI median 19.9%; Turbuhaler median 21.4%). At high flow rate (peak inspiratory flow rate 99 L x min(-1)) the AM-MDPI delivered significantly more drug to the lung (median 32.1% of metered dose) than at 65 L x min(-1) or 54 L x min(-1) (median 25.0% and 19.9% of metered dose, respectively), thus demonstrating flow rate dependence. The pattern of regional lung deposition from the AM-MDPI was similar for all three inhalation manoeuvres. It was concluded that the ASTA Medica multi-dose dry powder inhaler achieves at least as much deposition of budesonide in the lungs as a Turbuhaler when used at similar inspiratory flow rates.
Mechanisms of Anabolic Therapies for Osteoporosis
Authors: Ernesto Canalis, Andrea Giustina, John P. Bilezikian
Journal: New England Journal of Medicine (2007)

Antiresorptive agents help to restore skeletal balance by reducing bone turnover, primarily at the tissue level. Another therapeutic approach is to enhance bone formation with the use of anabolic agents, which differ fundamentally from antiresorptive drugs in their primary mechanism of action. This article reviews the mechanisms of polypeptide anabolic agents and strontium as potential therapeutic options for osteoporosis.
Apixaban for Extended Treatment of Venous Thromboembolism
Authors: Giancarlo Agnelli, Harry R. Buller, Alexander Cohen, Madelyn Curto, Alexander S. Gallus, Margot Johnson, Anthony Porcari, Gary E. Raskob, Jeffrey I. Weitz
Journal: New England Journal of Medicine (2012)

Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism.
Skin and oral fibroblasts exhibit phenotypic differences in extracellular matrix reorganization and matrix metalloproteinase activity
Authors: P. Stephens, K.J. Davies, N. Occleston, R.D. Pleass, C. Kon, J. Daniels, P.T. Khaw, D.W. Thomas
Journal: British Journal of Dermatology (2001)

Background Oral mucosal wounds are characterized by rapid re‐epithelialization and remodelling. In vitro, oral mucosal fibroblasts exhibit a fetal phenotype with increased extracellular matrix reorganizational ability, migration and experimental wound repopulation when compared with skin fibroblasts. Objectives To investigate whether phenotypic differences in the expression and production of matrix metalloproteinase (MMP) ‐2 and tissue inhibitors of metalloproteinases (TIMPs) could play an important part in mediating these in vitro differences. Methods Skin and oral mucosal fibroblast MMP‐2, TIMP‐1 and TIMP‐2 mRNA expression and protein production were studied in three‐dimensional collagen lattices using quantitative competitive reverse transcriptase–polymerase chain reaction (QCRT–PCR), enzyme‐linked immunosorbent assay (ELISA), zymography and reverse zymography. Results Oral mucosal fibroblasts exhibited increased levels of the 62‐kDa active form of MMP‐2 and lattice contraction when compared with skin fibroblasts. Oral mucosal and skin fibroblast MMP‐2 gene expression and synthesis of the 72‐kDa pro‐MMP‐2 was similar as assessed by QCRT–PCR, zymography and ELISA. Differential MMP‐2 activation was, however, related to phenotypic differences in TIMP activity between the skin and oral mucosal fibroblasts, as assessed by reverse zymography. Conclusions These studies propose a mechanism by which fibroblast phenotype may contribute directly to the observed preferential remodelling of oral wounds.
Methylation and Silencing of Protein Tyrosine Phosphatase Receptor Type O in Chronic Lymphocytic Leukemia
Authors: Tasneem Motiwala, Sarmila Majumder, Huban Kutay, David Spencer Smith, Donna S. Neuberg, David M. Lucas, John C. Byrd, Michael Grever, Samson T. Jacob
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Previous studies in our laboratory have shown the progressive methylation and suppression of the gene encoding protein tyrosine phosphatase, PTPRO, in the livers of rats fed a methyl-deficient diet that induces hepatocarcinogenesis. Subsequently, we observed the methylation of PTPRO in primary human lung tumors and also showed its potential tumor suppressor characteristics. The present study was undertaken to investigate whether the truncated form of PTPRO (PTPROt), specifically expressed in naïve B lymphocytes, was also methylated and suppressed in chronic lymphocytic leukemia (CLL), a disease generally affecting B lymphocytes. Experimental Design and Results: Initial screening showed that 60% of the 52 CLL samples analyzed using methylation-specific PCR assay were methylated compared with B lymphocytes from normal individuals, which were not methylated. The expression of PTPROt, as measured by semiquantitative reverse transcription-PCR, inversely correlated with methylation in the few samples tested. Analysis of additional samples (n = 50) by combined bisulfite restriction analysis showed that the PTPRO CpG island was methylated in 82% of patients with CLL compared with B lymphocytes from normal individuals. Furthermore, overall expression of PTPRO was reduced in CLL relative to normal lymphocytes. The PTPRO gene was also suppressed by methylation in the CLL cell line WaC3CD5, where it could be reactivated upon treatment with the DNA hypomethylating agent 5-AzaC. Ectopic expression of PTPROt in a nonexpressing cell line increased growth inhibition with fludarabine treatment, a therapy commonly used for CLL. Conclusion: This study reveals the potential role of PTPRO methylation and silencing in CLL tumorigenesis and also provides a novel molecular target in the epigenetic therapy.
Immobilization of Actively Thromboresistant Assemblies on Sterile Blood‐Contacting Surfaces
Authors: Zheng Qu, Venkat Krishnamurthy, Carolyn A. Haller, Brent M. Dorr, Ulla M. Marzec, Sawan Hurst, Monica T. Hinds, Stephen R. Hanson, David R. Liu, Elliot L. Chaikof
Journal: Advanced Healthcare Materials (2013)

Rapid one-step modification of thrombomodulin with alkylamine derivatives such as azide, biotin, and PEG is achieved using an evolved sortase (eSrtA) mutant. The feasibility of a point-of-care scheme is demonstrated herein to site-specifically immobilize azido-thrombomodulin on sterilized commercial ePTFE vascular grafts, which exhibit superior thromboresistance compared with commercial heparin-coated grafts in a primate model of acute graft thrombosis. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
CURB-65 and mortality in pneumonic and non-pneumonic exacerbations of COPD
Authors: John Steer, G. John Gibson, Stephen C. Bourke
Journal: European Respiratory Journal (2011)

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) requiring hospitalisation are often complicated by consolidation. In patients with pneumonia and AECOPD (pAECOPD) the CURB-65 prediction tool is widely used yet its utility in this population is uncertain.

Objective: To assess the effect of pneumonia on outcome, and the utility of CURB-65, in AECOPD.

Method: Patients hospitalised with AECOPD were recruited prospectively, with clinical data and CURB-65 collected on admission. Pneumonia was defined as the presence of new consolidation visible radiographically.

Results: Of 920 patients recruited, 299 (32.5%) had complicating pneumonia. Patients with pAECOPD were significantly older (mean age 75.7 v. 71.8 years); more often male (50.8% v. 43.8%); and had slightly better preserved ventilatory function (FEV1 45.5 v. 42.9% predicted).

In-hospital mortality was higher in pAECOPD than npAECOPD (20.1% versus 6%; p<0.001) and mortality for each CURB-65 group is shown in table 1:

View this table:

Mortality for CURB-65 groups





Area under the ROC curve for CURB-65 against in-hospital mortality was 0.66 (95% CI 0.58–0.74) for pAECOPD and 0.72 (95% CI 0.63–0.81) for npAECOPD.

Conclusion: In pAECOPD, risk of death is significantly greater than npAECOPD, and is higher than predicted by CURB-65. CURB-65 is a less good predictor of in-hospital mortality in pAECOPD than previously reported in CAP, and other prediction tools may be required for this population.
β-Catenin Status Predicts a Favorable Outcome in Childhood Medulloblastoma: The United Kingdom Children's Cancer Study Group Brain Tumour Committee
Authors: David W. Ellison, Olabisi E. Onilude, Janet C. Lindsey, Meryl E. Lusher, Claire L. Weston, Roger E. Taylor, Andrew D. Pearson, Steven C. Clifford
Journal: Journal of Clinical Oncology (2005)

Purpose Identifying pathobiological correlates of clinical behavior or therapeutic response currently represents a key challenge for medulloblastoma research. Nuclear accumulation of the β-catenin protein is associated with activation of the Wnt/Wg signaling pathway, and mutations affecting components of this pathway have been reported in approximately 15% of sporadic medulloblastomas. We tested the hypothesis that nuclear immunoreactivity for β-catenin is a prognostic marker in medulloblastoma, and assessed the relationship between nuclear β-catenin immunoreactivity and mutations of CTNNB1 and APC. Patients and Methods Medulloblastomas from children entered onto the International Society for Pediatric Oncology (SIOP)/United Kingdom Children's Cancer Study Group (UKCCSG) PNET3 trial (n = 109) were examined for β-catenin immunoreactivity, and where tissue was available, evidence of CTNNB1 and APC mutations. The results were correlated with clinicopathologic variables, principally outcome. Results Children with medulloblastomas that showed a nucleopositive β-catenin immunophenotype (27 of 109; 25%) had significantly better overall (OS) and event-free (EFS) survivals than children with tumors that showed either membranous/cytoplasmic β-catenin immunoreactivity or no immunoreactivity (P = .0015 and P = .0026, respectively). For β-catenin nucleopositive and nucleonegative medulloblastomas, 5-year OS was 92.3% (95% CI, 82% to 100%) versus 65.3% (95% CI, 54.8 to 75.7%), and 5-year EFS was 88.9% (95% CI, 77% to 100%) versus 59.5% (95% CI, 48.8 to 70.2%), respectively. Mutations in CTNNB1 were found exclusively among medulloblastomas that demonstrated nuclear β-catenin immunoreactivity, but no evidence of APC mutation was found in these cases. All children with β-catenin nucleopositive large cell/anaplastic medulloblastomas and β-catenin nucleopositive medulloblastomas presenting with metastatic disease are alive at least 5 years postdiagnosis. Conclusion Nuclear accumulation of β-catenin appears to be a marker of favorable outcome in medulloblastoma, and should be investigated further in large group-wide trials.