tbuckley/cabot-search huggingface dataset:
Accelerated Loss of Skeletal Muscle Strength in Older Adults With Type 2 Diabetes
Authors: Seok Won Park, Bret H. Goodpaster, Elsa S. Strotmeyer, Lewis H. Kuller, Robert Broudeau, Candace Kammerer, Nathalie de Rekeneire, Tamara B. Harris, Ann V. Schwartz, Frances A. Tylavsky, Yong-wook Cho, Anne B. Newman
Journal: Diabetes Care (2007)

OBJECTIVE—It has been shown that adults with either long-standing type 1 or type 2 diabetes had lower skeletal muscle strength than nondiabetic adults in cross-sectional studies. The aim of the study was to investigate longitudinal changes of muscle mass and strength in community-dwelling older adults with and without type 2 diabetes. RESEARCH DESIGN AND METHODS—We examined leg and arm muscle mass and strength at baseline and 3 years later in 1,840 older adults aged 70–79 years in the Health, Aging, and Body Composition Study. Regional muscle mass was measured by dual energy X-ray absorptiometry, and muscle strength was measured using isokinetic and isometric dynamometers. RESULTS—Older adults with type 2 diabetes (n = 305) showed greater declines in the leg muscle mass (−0.29 ± 0.03 vs. −0.23 ± 0.01 kg, P &amp;lt; 0.05) and strength (−16.5 ± 1.2 vs. −12.4 ± 0.5 Nm, P = 0.001) compared with older adults without diabetes. Leg muscle quality, expressed as maximal strength per unit of muscle mass (Newton meters per kilogram), also declined more rapidly in older adults with diabetes (−1.6 ± 0.2 vs. −1.2 ± 0.1 Nm/kg, P &amp;lt; 0.05). Changes in arm muscle strength and quality were not different between those with and without diabetes. Rapid declines in leg muscle strength and quality were attenuated but remained significant after controlling for demographics, body composition, physical activity, combined chronic diseases, interleukin-6, and tumor necrosis factor-α. CONCLUSIONS—In older adults, type 2 diabetes is associated with accelerated loss of leg muscle strength and quality.
Development of monoclonal antibodies and quantitative ELISAs targeting insulin-degrading enzyme
Authors: Anthony DelleDonne, Naomi Kouri, Lael Reinstatler, Tomoko Sahara, Lilin Li, Ji Zhao, Dennis W Dickson, Nilufer Ertekin-Taner, Malcolm A Leissring
Journal: Molecular Neurodegeneration (2009)

Insulin-degrading enzyme (IDE) is a widely studied zinc-metalloprotease implicated in the pathogenesis of type 2 diabetes mellitus, Alzheimer disease (AD) and varicella zoster virus infection. Despite more than six decades of research on IDE, progress has been hampered by the lack of well-characterized reagents targeting this biomedically important protease. To address this important need, we generated and characterized new mouse monoclonal antibodies (mAbs) targeting natively folded human and rodent IDE.Eight monoclonal hybridoma cell lines were derived in house from mice immunized with full-length, natively folded, recombinant human IDE. The mAbs derived from these lines were shown to detect IDE selectively and sensitively by a wide range of methods. Two mAbs in particular-designated 6A1 and 6H9-proved especially selective for IDE in immunocytochemical and immunohistochemical applications. Using a variety of methods, we show that 6A1 selectively detects both human and rodent IDE, while 6H9 selectively detects human, but not rodent, IDE, with both mAbs showing essentially no cross reactivity with other proteins in these applications. Using these novel anti-IDE mAbs, we also developed sensitive and quantitative sandwich ELISAs capable of quantifying IDE levels present in human brain extracts.We succeeded in developing novel mAbs that selectively detect rodent and/or human IDE, which we have shown to be suitable for a wide range of applications, including western blotting, immunoprecipitation, immunocytochemistry, immunohistochemistry, and quantitative sandwich ELISAs. These novel anti-IDE mAbs and the assays derived from them constitute important new tools for addressing many unresolved questions about the basic biology of IDE and its role in multiple highly prevalent human diseases.
Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis
Authors: Andreas Schapowal
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To compare the efficacy and tolerability of butterbur (<i>Petasites hybridus</i>) with cetirizine in patients with seasonal allergic rhinitis (hay fever). <b>Design:</b> Randomised, double blind, parallel group comparison. <b>Setting:</b> Four outpatient general medicine and allergy clinics in Switzerland and Germany. <b>Participants:</b> 131 patients were screened for seasonal allergic rhinitis and 125 patients were randomised (butterbur 61; cetirizine 64). <b>Interventions:</b> Butterbur (carbon dioxide extract tablets, ZE 339) one tablet, four times daily, or cetirizine, one tablet in the evening, both given for two consecutive weeks. <b>Main outcome measures:</b> Scores on SF-36 questionnaire and clinical global impression scale. <b>Results:</b> Improvement in SF-36 score was similar in the two treatment groups for all items tested hierarchically. Butterbur and cetirizine were also similarly effective with regard to global improvement scores on the clinical global impression scale (median score 3 in both groups). Both treatments were well tolerated. In the cetirizine group, two thirds (8/12) of reported adverse events were associated with sedative effects (drowsiness and fatigue) despite the drug being considered a non-sedating antihistamine. <b>Conclusions:</b> The effects of butterbur are similar to those of cetirizine in patients with seasonal allergic rhinitis when evaluated blindly by patients and doctors. Butterbur should be considered for treating seasonal allergic rhinitis when the sedative effects of antihistamines need to be avoided. <h3>What is already known on this topic</h3> Seasonal allergic rhinitis (hay fever) is common in countries with temperate climates. Most patients have their symptoms treated for short periods, particularly during peaks in atmospheric pollen count <h3>What this study adds</h3> After two weeks, the effects of butterbur and cetirizine were comparable in patients with hay fever Butterbur produced fewer sedating effects than cetirizine Butterbur should be considered when the sedating effects of antihistamines must be avoided
Relationship of DNA Methylation and Gene Expression in Idiopathic Pulmonary Fibrosis
Authors: Ivana V. Yang, Brent S. Pedersen, Einat Rabinovich, Corinne E. Hennessy, Elizabeth J. Davidson, Elissa Murphy, Brenda Juan Guardela, John R. Tedrow, Yingze Zhang, Mandal K. Singh, Mick Correll, Marvin I. Schwarz, Mark Geraci, Frank C. Sciurba, John Quackenbush, Avrum Spira, Naftali Kaminski, David A. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Idiopathic pulmonary fibrosis (IPF) is an untreatable and often fatal lung disease that is increasing in prevalence and is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control gene expression and are likely to regulate the IPF transcriptome.
Surgery or radiotherapy for prostate cancer?
Authors: A. Rane
Journal: BMJ (2014)

Surgery appears to be associated with better survival for men with localised disease

Prostate cancer is the commonest malignancy in males in the Western world, accounting for over a quarter of all cancer diagnoses in men in the United Kingdom; more than 90% of new diagnoses of prostate cancer are of localised disease.1 Surprisingly, we do not objectively yet know the best form of treatment for this prevalent disease. In a linked paper, Sooriakumaran and colleagues (doi:10.1136/bmj.g1502) present some of the best quality evidence so far by comparing radical prostatectomy and radiotherapy, the two most widely used treatments.2 Although previous investigators have evaluated the comparative effectiveness of treatments, most such reports were arguably flawed by lack of complete and accurate data on certain key variables that would help predict mortality. Indeed, guidelines from England’s National Institute for Health and Care Excellence, updated just last month, make no suggestion as to which treatment is preferred and simply encourage decision making to be based on differences in adverse event profiles.3 

The only two …
Phase II study of XR5000 (DACA) administered as a 120-h infusion in patients with recurrent glioblastoma multiforme
Authors: C. Twelves, M. Campone, B. Coudert, M. Van den Bent, M. de Jonge, C. Dittrich, R. Rampling, R. Sorio, D. Lacombe, C. de Balincourt, P. Fumoleau
Journal: Annals of Oncology (2002)
Interaction of Chemokine Receptor CCR5 with its Ligands: Multiple Domains for HIV-1 gp120 Binding and a Single Domain for Chemokine Binding
Authors: Lijun Wu, Greg LaRosa, Nasim Kassam, Cynthia J. Gordon, Heidi Heath, Nancy Ruffing, Howard Chen, Jason Humblias, Michel Samson, Marc Parmentier, John P. Moore, Charles R. Mackay
Journal: The Journal of Experimental Medicine (1997)

CCR5 is a chemokine receptor expressed by T cells and macrophages, which also functions as the principal coreceptor for macrophage (M)-tropic strains of HIV-1. To understand the molecular basis of the binding of chemokines and HIV-1 to CCR5, we developed a number of mAbs that inhibit the various interactions of CCR5, and mapped the binding sites of these mAbs using a panel of CCR5/CCR2b chimeras. One mAb termed 2D7 completely blocked the binding and chemotaxis of the three natural chemokine ligands of CCR5, RANTES (regulated on activation normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1α, and MIP-1β, to CCR5 transfectants. This mAb was a genuine antagonist of CCR5, since it failed to stimulate an increase in intracellular calcium concentration in the CCR5 transfectants, but blocked calcium responses elicited by RANTES, MIP-1α, or MIP-1β. This mAb inhibited most of the RANTES and MIP-1α chemotactic responses of activated T cells, but not of monocytes, suggesting differential usage of chemokine receptors by these two cell types. The 2D7 binding site mapped to the second extracellular loop of CCR5, whereas a group of mAbs that failed to block chemokine binding all mapped to the NH2-terminal region of CCR5. Efficient inhibition of an M-tropic HIV-1–derived envelope glycoprotein gp120 binding to CCR5 could be achieved with mAbs recognizing either the second extracellular loop or the NH2-terminal region, although the former showed superior inhibition. Additionally, 2D7 efficiently blocked the infectivity of several M-tropic and dual-tropic HIV-1 strains in vitro. These results suggest a complicated pattern of HIV-1 gp120 binding to different regions of CCR5, but a relatively simple pattern for chemokine binding. We conclude that the second extracellular loop of CCR5 is an ideal target site for the development of inhibitors of either chemokine or HIV-1 binding to CCR5.
Ribosomal Protein S6 Kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein
Authors: Qi Ma, Sunny Guin, Snehal S Padhye, Yong-Qing Zhou, Rui-Wen Zhang, Ming-Hai Wang
Journal: Molecular Cancer (2011)

Abstract Background Epithelial to mesenchymal transition (EMT) occurs during cancer cell invasion and malignant metastasis. Features of EMT include spindle-like cell morphology, loss of epithelial cellular markers and gain of mesenchymal phenotype. Activation of the RON receptor tyrosine kinase by macrophage-stimulating protein (MSP) has been implicated in cellular EMT program; however, the major signaling determinant(s) responsible for MSP-induced EMT is unknown. Results The study presented here demonstrates that RSK2, a downstream signaling protein of the Ras-Erk1/2 pathway, is the principal molecule that links MSP-activated RON signaling to complete EMT. Using MDCK cells expressing RON as a model, a spindle-shape based screen was conducted, which identifies RSK2 among various intracellular proteins as a potential signaling molecule responsible for MSP-induced EMT. MSP stimulation dissociated RSK2 with Erk1/2 and promoted RSK2 nuclear translocation. MSP strongly induced RSK2 phosphorylation in a dose-dependent manner. These effects relied on RON and Erk1/2 phosphorylation, which is significantly potentiated by transforming growth factor (TGF)-β1, an EMT-inducing cytokine. Specific RSK inhibitor SL0101 completely prevented MSP-induced RSK phosphorylation, which results in inhibition of MSP-induced spindle-like morphology and suppression of cell migration associated with EMT. In HT-29 cancer cells that barely express RSK2, forced RSK2 expression results in EMT-like phenotype upon MSP stimulation. Moreover, specific siRNA-mediated silencing of RSK2 but not RSK1 in L3.6pl pancreatic cancer cells significantly inhibited MSP-induced EMT-like phenotype and cell migration. Conclusions MSP-induced RSK2 activation is a critical determinant linking RON signaling to cellular EMT program. Inhibition of RSK2 activity may provide a therapeutic opportunity for blocking RON-mediated cancer cell migration and subsequent invasion.
Are we meeting the standards set for endoscopy? Results of a large-scale prospective survey of endoscopic retrograde cholangio-pancreatograph practice
Authors: E. J Williams, S. Taylor, P. Fairclough, A. Hamlyn, R. F Logan, D. Martin, S. A Riley, P. Veitch, M. Wilkinson, P. J Williamson, M. Lombard
Journal: Gut (2006)

<b>Objective:</b> To examine endoscopic retrograde cholangio-pancreatography (ERCP) services and training in the UK. <b>Design:</b> Prospective multicentre survey. <b>Setting:</b> Five regions of England. <b>Participants:</b> Hospitals with an ERCP unit. <b>Outcome measures:</b> Adherence to published guidelines, technical success rates, complications and mortality. <b>Results:</b> Organisation questionnaires were returned by 76 of 81 (94%) units. Personal questionnaires were returned by 190 of 213 (89%) ERCP endoscopists and 74 of 91 (81%) ERCP trainees, of whom 45 (61%) reported participation in &lt;50 ERCPs per annum. In all, 66 of 81 (81%) units collected prospective data on 5264 ERCPs, over a mean period of 195 days. Oximetry was used by all units, blood pressure monitoring by 47 of 66 (71%) and ECG monitoring by 37 of 66 (56%) units; 1484 of 4521 (33%) patients were given &gt;5 mg of midalozam. Prothrombin time was recorded in 4539 of 5264 (86%) procedures. Antibiotics were given in 1021 of 1412 (72%) cases, where indicated. Patients’ American Society of Anesthesiology (ASA) scores were 3–5 in 670 of 5264 (12.7%) ERCPs, and 4932 of 5264 (94%) ERCPs were scheduled with therapeutic intent. In total, 140 of 182 (77%) trained endoscopists demonstrated a cannulation rate ⩾80%. The recorded cannulation rate among senior trainees (with an experience of &gt;200 ERCPs) was 222/338 (66%). Completion of intended treatment was done in 3707 of 5264 (70.4%) ERCPs; 268 of 5264 (5.1%) procedures resulted in a complication. Procedure-related mortality was 21/5264 (0.4%). Mortality correlated with ASA score. <b>Conclusion:</b> Most ERCPs in the UK are performed on low-risk patients with therapeutic intent. Complication rates compare favourably with those reported internationally. However, quality suffers because there are too many trainees in too many low-volume ERCP centres.
Prolyl Isomerase Pin1 Acts Downstream of miR200c to Promote Cancer Stem–like Cell Traits in Breast Cancer
Authors: Man-Li Luo, Chang Gong, Chun-Hau Chen, Daniel Y. Lee, Hai Hu, Pengyu Huang, Yandan Yao, Wenjun Guo, Ferenc Reinhardt, Gerburg Wulf, Judy Lieberman, Xiao Zhen Zhou, Erwei Song, Kun Ping Lu
Journal: Cancer Research (2014)

Abstract Breast cancer stem–like cells (BCSC) have been implicated in tumor growth, metastasis, drug resistance, and relapse but druggable targets in appropriate subsets of this cell population have yet to be identified. Here we identify a fundamental role for the prolyl isomerase Pin1 in driving BCSC expansion, invasiveness, and tumorigenicity, defining it as a key target of miR200c, which is known to be a critical regulator in BCSC. Pin1 overexpression expanded the growth and tumorigenicity of BCSC and triggered epithelial–mesenchymal transition. Conversely, genetic or pharmacological inhibition of Pin1 reduced the abundance and self-renewal activity of BCSC. Moreover, moderate overexpression of miR200c-resistant Pin1 rescued the BCSC defect in miR200c-expressing cells. Genetic deletion of Pin1 also decreased the abundance and repopulating capability of normal mouse mammary stem cells. In human cells, freshly isolated from reduction mammoplasty tissues, Pin1 overexpression endowed BCSC traits to normal breast epithelial cells, expanding both luminal and basal/myoepithelial lineages in these cells. In contrast, Pin1 silencing in primary breast cancer cells freshly isolated from clinical samples inhibited the expansion, self-renewal activity, and tumorigenesis of BCSC in vitro and in vivo. Overall, our work demonstrated that Pin1 is a pivotal regulator acting downstream of miR200c to drive BCSC and breast tumorigenicity, highlighting a new therapeutic target to eradicate BCSC. Cancer Res; 74(13); 3603–16. ©2014 AACR.
New diagnosis and subsequent post-partum radiological improvement of lymphangioleiomyomatosis
Authors: G Hagan, P Lawford
Journal: Thorax (2009)

New diagnosis and subsequent post-partum radiological improvement of lymphangioleiomyomatosisA 39-year-old nulliparous woman became breathless after a caesarean section.CT pulmonary angiography (fig 1) showed no filling defect but cysts, small bilateral effusions and thickened interlobular septa were visible consistent with a possible diagnosis of lymphangioleiomyomatosis (LAM).An open lung biopsy performed 11 months later showed that the lung parenchyma contained scattered cysts of various sizes with proliferative smooth muscle bundles in the cyst walls staining for smooth muscle actin and HMB45, which confirmed a diagnosis of LAM.It is thought that the interstitial infiltrates were secondary to LAM.Cardiac failure may have a similar CT appearance, but the patient had no risk factors apart from recent pregnancy, improved with no anti-failure medication and did not have lung crepitations when auscultated in the immediate postoperative period.A follow-up CT scan of the thorax 14 months later (fig 2) showed that the reticular shadowing and pleural effusions had disappeared.
Obesity and Breast Cancer Prognosis: Weight of the Evidence
Authors: Frank A. Sinicrope, Andrew J. Dannenberg
Journal: Journal of Clinical Oncology (2010)

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Tumor Vascular Microenvironment Determines Responsiveness to Photodynamic Therapy
Authors: Amanda L. Maas, Shirron L. Carter, E. Paul Wileyto, Joann Miller, Min Yuan, Guoqiang Yu, Amy C. Durham, Theresa M. Busch
Journal: Cancer Research (2012)

Abstract The efficacy of photodynamic therapy (PDT) depends upon the delivery of both photosensitizing drug and oxygen. In this study, we hypothesized that local vascular microenvironment is a determinant of tumor response to PDT. Tumor vascularization and its basement membrane (collagen) were studied as a function of supplementation with basement membrane matrix (Matrigel) at the time of tumor cell inoculation. Effects on vascular composition with consequences to tumor hypoxia, photosensitizer uptake, and PDT response were measured. Matrigel-supplemented tumors developed more normalized vasculature, composed of smaller and more uniformly spaced blood vessels than their unsupplemented counterparts, but these changes did not affect tumor oxygenation or PDT-mediated direct cytotoxicity. However, PDT-induced vascular damage increased in Matrigel-supplemented tumors, following an affinity of the photosensitizer Photofrin for collagen-containing vascular basement membrane coupled with increased collagen content in these tumors. The more highly collagenated tumors showed more vascular congestion and ischemia after PDT, along with a higher probability of curative outcome that was collagen dependent. In the presence of photosensitizer-collagen localization, PDT effects on collagen were evidenced by a decrease in its association with vessels. Together, our findings show that photosensitizer localization to collagen increases vascular damage and improves treatment efficacy in tumors with greater collagen content. The vascular basement membrane is thus identified to be a determinant of therapeutic outcome in PDT of tumors. Cancer Res; 72(8); 2079–88. ©2012 AACR.
Tuberculosis transmission patterns among Spanish-born and foreign-born populations in the city of Barcelona
Authors: S. Borrell, G. Tudó, E. Rey, J. González-Martín, M. Español, F. March, P. Coll, A. Orcau, J.A. Caylà, J.M. Jansà, F. Alcaide, N. Martín-Casabona, M. Salvadó, J.A. Martinez, R. Vidal, F. Sanchez, N. Altet
Journal: Clinical Microbiology and Infection (2009)