tbuckley/cabot-search huggingface dataset:
Multifunctional Peptide-Conjugated Hybrid Silica Nanoparticles for Photodynamic Therapy and MRI
Authors: Hamanou Benachour, Aymeric Sève, Thierry Bastogne, Céline Frochot, Régis Vanderesse, Jordane Jasniewski, Imen Miladi, Claire Billotey, Olivier Tillement, François Lux, Muriel Barberi-Heyob
Journal: Theranostics (2012)

Photodynamic therapy (PDT) is an emerging theranostic modality for various cancer as well as non-cancer diseases.Its efficiency is mainly based on a selective accumulation of PDT and imaging agents in tumor tissue.The vascular effect is widely accepted to play a major role in tumor eradication by PDT.To promote this vascular effect, we previously demonstrated the interest of using an active-targeting strategy targeting neuropilin-1 (NRP-1), mainly over-expressed by tumor angiogenic vessels.For an integrated vascular-targeted PDT with magnetic resonance imaging (MRI) of cancer, we developed multifunctional gadolinium-based nanoparticles consisting of a surface-localized tumor vasculature targeting NRP-1 peptide and polysiloxane nanoparticles with gadolinium chelated by DOTA derivatives on the surface and a chlorin as photosensitizer.The nanoparticles were surface-functionalized with hydrophilic DOTA chelates and also used as a scaffold for the targeting peptide grafting.In vitro investigations demonstrated the ability of multifunctional nanoparticles to preserve the photophysical properties of the encapsulated photosensitizer and to confer photosensitivity to MDA-MB-231 cancer cells related to photosensitizer concentration and light dose.Using binding test, we revealed the ability of peptide-functionalized nanoparticles to target NRP-1 recombinant protein.Importantly, after intravenous injection of the multifunctional nanoparticles in rats bearing intracranial U87 glioblastoma, a positive MRI contrast enhancement was specifically observed in tumor tissue.Real-time MRI analysis revealed the ability of the targeting peptide to confer specific intratumoral retention of the multifunctional nanoparticles.
Phase III study of nilotinib versus best supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinib
Authors: P. Reichardt, J.-Y. Blay, H. Gelderblom, M. Schlemmer, G.D. Demetri, B. Bui-Nguyen, G.A. McArthur, S. Yazji, Y. Hsu, I. Galetic, P. Rutkowski
Journal: Annals of Oncology (2012)
The murine H-2.7 specificity is an antigenic determinant of C4d, a fragment of the fourth component of the complement system.
Authors: A Ferreira, C S David, V Nussenzweig
Journal: The Journal of Experimental Medicine (1980)

The S region of H-2 controls a polymorphism of the gamma-chain of C4 (gamma 1, gamma 2, and gamma 3) as shown by differences in their isoelectric points. The G region of H-2 was defined by the presence of an alloantigen (H-2.7) on erythrocytes and serum. We found that antisera to H-2.7 immunoprecipitated C4 and no other protein from mouse EDTA-plasma. Furthermore, all H-2.7-positive strains bear C4-gamma 1, and conversely, H-2.7-negative mice bear C4-gamma 2 or gamma 3 (with one exception; see below). The H-2.7 specificity resides on C4d, a 45,000-mol wt fragment generated from the cleavage of the alpha'-chain of C4b by serum control proteins. Because the C4d fragment bears the labile binding site of C4 for cell membranes, it is likely that the erythrocyte alloantigen is acquired from serum as a result of the activation of C4. On the basis of these findings, the existence of a separate G locus is unlikely. Our results also show that C4-gamma 1 and C4-gamma 2 differ from each other at least in their alpha- and gamma-chains, and may represent complex allotypes. No trans effects were observed in F1 hybrids between H-2.7-positive and -negative mice. Mice that bear the k allele in the S region are exceptional in two respects: they are C4-deficient and their C4 molecules bear gamma 2 chains and the H-2.7 alloantigen. Perhaps the low levels of C4 are a consequence of the genetic event leading to this unusual alpha-gamma-chain combination.
The Abnormal Serum Lipid Pattern in Patients with Coronary Arteriosclerosis
Authors: ALFRED STEINER, FORREST E. KENDALL, JAMES A. L. MATHERS
Journal: Circulation (1952)

Studies in experimental arteriosclerosis have indicated that the relative level of serum lipid phosphorus may be as significant a factor as the absolute level of serum cholesterol in the production of arterial lesions. For this reason, the serum lipid pattern of 82 patients with coronary arteriosclerosis has been compared with that of 112 healthy adults. An elevation of the serum cholesterol, serum lipid phosphorus and the serum cholesterol-lipid phosphorus molar ratio has been found in most of the patients with coronary arteriosclerosis.
The GRAF family member oligophrenin1 is a RhoGAP with BAR domain and regulates Rho GTPases in platelets
Authors: Margitta Elvers, Sandra Beck, Anna Fotinos, Melanie Ziegler, Meinrad Gawaz
Journal: Cardiovascular Research (2012)

Platelet adhesion and aggregation is essential for haemostasis and thrombosis. Cytoskeletal reorganization of activated platelets plays a crucial role in these processes and implies activation of Rho GTPases. Rho GTPases are regulated by GTPase-activating proteins (GAPs) that stimulate GTP hydrolysis to terminate Rho signalling. In this study, we explored the regulation of Rho GTPases in platelets. Oligophrenin1 (OPHN1) is a RhoGAP-regulating cytoplasmic protein that has been investigated in patients with X-linked mental retardation. Here, we identified OPHN1 in mouse platelets where it co-localizes to actin-rich regions and Rho GTPases. OPHN1 exhibits strong GTPase-stimulating activity towards RhoA, Cdc42, and Rac1 and regulates cell adhesion and spreading. Furthermore, OPHN1 controls RhoA-mediated stress fibre and focal adhesion formation as well as filopodia and lamellipodia development. The analysis of different domains of OPHN1 revealed distinct functions in Rho hydrolysis. The C-terminus of OPHN1 displays an essential unit for Rho regulation, whereas the PH domain is a regulatory unit of OPHN1 controlling GAP function. The N-terminal BAR (Bin/amphiphysin/Rvs)-like domain is involved in GAP regulation but not in cytoskeleton rearrangements or Rho regulation and acts as a guidance domain to direct this GAP to its substrate. Our results suggest that OPHN1 is a powerful regulator of Rho GTPase activity in platelets that is critical for the reorganization of the cytoskeleton, which is a major process required for stable platelet adhesion and thrombus formation to occur.
Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study
Authors: Darryl P Leong, Koon K Teo, Sumathy Rangarajan, Patricio Lopez-Jaramillo, Alvaro Avezum, Andres Orlandini, Pamela Seron, Suad H Ahmed, Annika Rosengren, Roya Kelishadi, Omar Rahman, Sumathi Swaminathan, Romaina Iqbal, Rajeev Gupta, Scott A Lear, Aytekin Oguz, Khalid Yusoff, Katarzyna Zatonska, Jephat Chifamba, Ehimario Igumbor, Viswanathan Mohan, Ranjit Mohan Anjana, Hongqiu Gu, Wei Li, Salim Yusuf
Journal: The Lancet (2015)
The secret life of steroids in asthma
Authors: P. J. Sterk, C. Y. Yick, A. M. Slats
Journal: European Respiratory Journal (2008)

Asthma is an inflammatory disease. Who is still questioning this paradigm? In the Global Initiative for Asthma (GINA) guidelines the disease is defined as a chronic inflammatory disorder of the airways 1. The evidence for this is overwhelming, and comes from observational studies as well as experimental models. The proof of the pudding has been provided by numerous studies with anti-inflammatory interventions. Ever since the early 1950s 2, the efficacy of both short courses and maintenance treatment with corticosteroids in asthma has been beyond any discussion 1. Hence, the evidence that inflammation is causally involved in the pathophysiology of asthma nicely meets Koch’s postulations.

Therefore, it is no surprise that ever since this key mechanism of the disease was identified, many academic and industrial groups rushed to develop the most selective and potent anti-inflammatory compounds for suppression, prevention or perhaps even cure of the disease. Remarkably, during the past 20 yrs the development of new anti-inflammatory therapies for asthma has been less successful than was hoped and expected 3. Can’t we identify the responsible inflammatory targets? Should such targets be combined? Certainly, this cannot be excluded and deserves an even more intensive search. But, is it not frustrating to see our neighbour rheumatologists successfully testing and implementing one novel anti-inflammatory after the other 4?

Of course, asthma is a complex disease, perhaps even more complex than arthritis. But what does that mean? If anything, that must be the key point. Complexity requires multi-dimensional approaches. Should we keep on addressing asthma as reductionists, or does the disease require a more integrative approach, by taking the elaborate dynamics of the organ and the organism into account rather than singling out molecular pathways? It seems that the puzzle of asthma demands the latter. Fortunately, we are moving on to …
Novel poly(amido amine)s with bioreducible disulfide linkages in their diamino-units: Structure effects and in vitro gene transfer properties
Authors: Martin Piest, Chao Lin, Miguel A. Mateos-Timoneda, Martin C. Lok, Wim E. Hennink, Jan Feijen, Johan F.J. Engbersen
Journal: Journal of Controlled Release (2008)
Cardiac differentiation in Xenopus is initiated by mespa
Authors: Maximilian C.M. Kriegmair, Stephanie Frenz, Marina Dusl, Wolfgang-M. Franz, Robert David, Ralph A.W. Rupp
Journal: Cardiovascular Research (2012)

Future cardiac repair strategies will require a profound understanding of the principles underlying cardiovascular differentiation. Owing to its extracorporal and rapid development, Xenopus laevis provides an ideal experimental system to address these issues in vivo. Whereas mammalian MesP1 is currently regarded as the earliest marker for the cardiovascular system, several MesP1-related factors from Xenopus—mespa, mespb, and mespo—have been assigned only to somitogenesis so far. We, therefore, analysed these genes comparatively for potential contributions to cardiogenesis. RNA in situ hybridizations revealed a novel anterior expression domain exclusively occupied by mespa during gastrulation, which precedes the prospective heart field. Correspondingly, when overexpressed mespa most strongly induced cardiac markers in vivo as well as ex vivo. Transference to murine embryonic stem (ES) cells and subsequent FACS analyses for Flk-1 and Troponin I confirmed the high potential of mespa as a cardiac inducer. In vivo, Morpholino-based knockdown of mespa protein led to a dramatic loss of pro-cardiac and sarcomeric markers, which could be rescued either by mespa itself or human MesP1, but neither by mespb nor mespo. Epistatic analysis positioned mespa upstream of mespo and mespb, and revealed positive autoregulation for mespa at the time of its induction. Our findings contribute to the understanding of conserved events initiating vertebrate cardiogenesis. We identify mespa as functional amphibian homologue of mammalian MesP1. These results will enable the dissection of cardiac specification from the very beginning in the highly versatile Xenopus system.
Cigarette smoke exposure causes constriction of rat lung
Authors: JL Wright, JP Sun, A Churg
Journal: European Respiratory Journal (1999)

Cigarette smoke is known to cause acute increases in airway resistance, but the mechanisms behind this effect are unknown. Lung explants were utilized to examine the constrictive effects of acute cigarette smoke exposure on bronchioles from rats in vitro that had or had not been previously exposed to cigarette smoke in vivo. It was found that smoke induced a small but consistent degree of contraction of the airways in vitro, which could be reduced by an endothelin receptor antagonist in the animals which had had no previous smoke exposure in vivo, and reduced by the oxidant scavengers superoxide dismutase or catalase in the animals with previous smoke exposure. In conclusion, cigarette smoke induces acute small airways constriction through both endothelin release and direct oxidant effects; which mechanisms are operative depends on the prior smoking status.
The effects of combined micron-/submicron-scale surface roughness and nanoscale features on cell proliferation and differentiation
Authors: Rolando A. Gittens, Taylor McLachlan, Rene Olivares-Navarrete, Ye Cai, Simon Berner, Rina Tannenbaum, Zvi Schwartz, Kenneth H. Sandhage, Barbara D. Boyan
Journal: Biomaterials (2011)
TRANSMISSION OF EPIDEMIC GASTROENTERITIS TO HUMAN VOLUNTEERS BY ORAL ADMINISTRATION OF FECAL FILTRATES
Authors: Irving Gordon, Hollis S. Ingraham, Robert F. Korns
Journal: The Journal of Experimental Medicine (1947)

Epidemic gastroenteritis was transmitted to human volunteers by the oral administration of fecal filtrates. The original inocula were obtained from patients in a natural outbreak which occurred at Marcy State Hospital in the winter of 1946-47. The experimental disease closely resembled that of the donors. The incubation period ranged from I to 5 days, with a mean of 3 days. The disease was carried through three generations, in the last two by means of fecal filtrates. Oral administration of unfiltered throat washings from experimental cases of the disease likewise induced gastroenteritis but subjects who inhaled a portion of the same throat washings remained asymptomatic. Volunteers who inhaled throat washings taken from patients in the epidemic at Marcy State Hospital also failed to develop the disease. Five volunteers who had previously been inoculated with fecal filtrates were reinoculated with the same material. Gastroenteritis followed in one of the two subjects who had failed to contract the disease the first time. The others remained well. Embryonated hens' eggs were inoculated with one of the two unfiltered stool suspensions used in the pool which had induced gastroenteritis in each of the three volunteers to whom it was fed. Three sets of eggs were inoculated: one on the chorioallantoic membrane, another into the yolk sac, and a third into the amniotic sac. Three serial passages were carried out by each method at varying time intervals. Penicillin and streptomycin were employed as antibacterial agents. Tissue and extraembryonic fluids from the third passage were non-infective for volunteers.
Interferon-induced 2'-5' adenylate synthetase in vivo and interferon production in vitro by lymphocytes from systemic lupus erythematosus patients with and without circulating interferon.
Authors: O T Preble, K Rothko, J H Klippel, R M Friedman, M I Johnston
Journal: The Journal of Experimental Medicine (1983)

The interferon (IFN)-induced enzyme 2-5A synthetase was elevated in mononuclear cells from both serum IFN-positive and -negative systemic lupus erythematosus (SLE) patients. This suggests that a much higher percentage of patients than previously thought produce endogenous IFN. These results may partly explain findings that mononuclear cells from SLE patients are deficient in IFN production in vitro in response to certain IFN inducers. Although normal lymphocytes can produce an acid-labile alpha IFN after stimulation with C. parvum in vitro, the reason for endogenous production of this unusual alpha IFN by SLE patients remains unknown.
Necrotizing Fasciitis Secondary to Community Pneumonia by Panton-Valentine Leukocidin–Positive Methicillin-Resistant <i>Staphylococcus aureus</i>
Authors: Dennis de Carvalho Ferreira, Ana Cristina Cisne Frota, Fernanda Sampaio Cavalcante, Eliane Dios Abad, Kátia Regina Netto dos Santos
Journal: American Journal of Respiratory and Critical Care Medicine (2012)
3-Methylcholanthrene and Other Aryl Hydrocarbon Receptor Agonists Directly Activate Estrogen Receptor α
Authors: Maen Abdelrahim, Eric Ariazi, Kyounghyun Kim, Shaheen Khan, Rola Barhoumi, Robert Burghardt, Shengxi Liu, Denise Hill, Richard Finnell, Bogdan Wlodarczyk, V. Craig Jordan, Stephen Safe
Journal: Cancer Research (2006)

Abstract 3-Methylcholanthrene (3MC) is an aryl hydrocarbon receptor (AhR) agonist, and it has been reported that 3MC induces estrogenic activity through AhR-estrogen receptor α (ERα) interactions. In this study, we used 3MC and 3,3′,4,4′,5-pentachlorobiphenyl (PCB) as prototypical AhR ligands, and both compounds activated estrogen-responsive reporter genes/gene products (cathepsin D) in MCF-7 breast cancer cells. The estrogenic responses induced by these AhR ligands were inhibited by the antiestrogen ICI 182780 and by the transfection of a small inhibitory RNA for ERα but were not affected by the small inhibitory RNA for AhR. These results suggest that 3MC and PCB directly activate ERα, and this was confirmed in a competitive ERα binding assay and in a fluorescence resonance energy transfer experiment in which PCB and 3MC induced CFP-ERα/YFP-ERα interactions. In a chromatin immunoprecipitation assay, PCB and 3MC enhanced ERα (but not AhR) association with the estrogen-responsive region of the pS2 gene promoter. Moreover, in AhR knockout mice, 3MC increased uterine weights and induced expression of cyclin D1 mRNA levels. These results show that PCB and 3MC directly activate ERα-dependent transactivation and extend the number of ligands that activate both AhR and ERα. (Cancer Res 2006; 66(4): 2459-67)
Growth Stimulation of BHK Cells in Culture by Free Biotin in Serum&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Merwin Moskowitz, David K. S. Cheng, David K. Moscatello, Haruki Otsuka
Journal: JNCI Journal of the National Cancer Institute (1980)

A dialysate of fetal bovine serum stimulated the growth of BHK cells in a medium containing 1% dialyzed serum. The growth-stimulating activity of the dialysate was separated in a single peak with Biogei P-2 chromatography, and a single active component was further fractionated with paper and thin-layer chromatography. The component was identified as biotin. Pure biotin behaved the same as the active component in the dialysate and had the same growth-stimulating activity. The dialysate contained only the free biotin that was present in serum. Free biotin was found in relatively large amounts in fetal (bovine and human) sera, and only a very small percentage of dialysates of adult (bovine, horse, swine, and human) sera had traces of growth-stimulating activity. The possible role of free biotin in the body is discussed.
Intrinsic Gluconeogenesis Is Enhanced in Renal Proximal Tubules of Zucker Diabetic Fatty Rats
Authors: Assaad Eid, Sophie Bodin, Bernard Ferrier, Hélène Delage, Michelle Boghossian, Mireille Martin, Gabriel Baverel, Agnès Conjard
Journal: Journal of the American Society of Nephrology (2006)

Recent studies indicate that renal gluconeogenesis is substantially stimulated in patients with type 2 diabetes, but the mechanism that is responsible for such stimulation remains unknown. Therefore, this study tested the hypothesis that renal gluconeogenesis is intrinsically elevated in the Zucker diabetic fatty rat, which is considered to be an excellent model of type 2 diabetes. For this, isolated renal proximal tubules from diabetic rats and from their lean nondiabetic littermates were incubated in the presence of physiologic gluconeogenic precursors. Although there was no increase in substrate removal and despite a reduced cellular ATP level, a marked stimulation of gluconeogenesis was observed in diabetic relative to nondiabetic rats, with near-physiologic concentrations of lactate (38%), glutamine (51%) and glycerol (66%). This stimulation was caused by a change in the fate of the substrate carbon skeletons resulting from an increase in the activities and mRNA levels of the key gluconeogenic enzymes that are common to lactate, glutamine, and glycerol metabolism, i.e., mainly of phosphoenolpyruvate carboxykinase and, to a lesser extent, of glucose-6-phosphatase and fructose-1,6-bisphosphatase. Experimental evidence suggests that glucocorticoids and cAMP were two factors that were responsible for the long-term stimulation of renal gluconeogenesis observed in the diabetic rats. These data provide the first demonstration in an animal model that renal gluconeogenesis is upregulated by a long-term mechanism during type 2 diabetes. Together with the increased renal mass (38%) observed, they lend support to the view so far based only on in vivo studies performed in humans that renal gluconeogenesis may be stimulated by and crucially contribute to the hyperglycemia of type 2 diabetes.
Role of Bcl-3 in solid tumors
Authors: Vilma Maldonado, Jorge Melendez-Zajgla
Journal: Molecular Cancer (2011)

Bcl-3 is an established oncogene in hematologic malignancies, such as B-cell chronic lymphocytic leukemias. Nevertheless, recent research has shown that it also participates in progression of diverse solid tumors. The present review summarizes the current knowledge of Bcl3 role in solid tumors progression, including some new insights in its possible molecular mechanisms of action.
Should the Health Community Promote Smokeless Tobacco (Snus) as a Harm Reduction Measure?
Authors: Coral E Gartner, Wayne D Hall, Simon Chapman, Becky Freeman
Journal: PLoS Medicine (2007)

Background to the Debate The tobacco control community is divided on whether or not to inform the public that using oral, smokeless tobacco (Swedish snus) is less hazardous to health than smoking tobacco. Proponents of "harm reduction" point to the Swedish experience. Snus seems to be widely used as an alternative to cigarettes in Sweden, say these proponents, contributing to the low overall prevalence of smoking and smoking-related disease. Harm reduction proponents thus argue that the health community should actively inform inveterate cigarette smokers of the benefits of switching to snus. However, critics of harm reduction say that snus has its own risks, that no form of tobacco should ever be promoted, and that Sweden's experience is likely to be specific to that culture and not transferable to other settings. Critics also remain deeply suspicious that the tobacco industry will use snus marketing as a "gateway" to promote cigarettes. In the interests of promoting debate, the authors (who are collaborators on a research project on the future of tobacco control) have agreed to outline the strongest arguments for and against promoting Swedish snus as a form of harm reduction.