tbuckley/cabot-search huggingface dataset:
Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques
Authors: Maulik D. Majmudar, Jeongsoo Yoo, Edmund J. Keliher, Jessica J. Truelove, Yoshiko Iwamoto, Brena Sena, Partha Dutta, Anna Borodovsky, Kevin Fitzgerald, Marcelo F. Di Carli, Peter Libby, Daniel G. Anderson, Filip K. Swirski, Ralph Weissleder, Matthias Nahrendorf
Journal: Circulation Research (2013)

Rationale: Myeloid cell content in atherosclerotic plaques associates with rupture and thrombosis. Thus, imaging of lesional monocytes and macrophages could serve as a biomarker of disease progression and therapeutic intervention. Objective: To noninvasively assess plaque inflammation with dextran nanoparticle (DNP)-facilitated hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). Methods and Results: Using clinically approved building blocks, we systematically developed 13-nm polymeric nanoparticles consisting of cross-linked short chain dextrans, which were modified with desferoxamine for zirconium-89 radiolabeling ( 89 Zr-DNP) and a near-infrared fluorochrome (VT680) for microscopic and cellular validation. Flow cytometry of cells isolated from excised aortas showed DNP uptake predominantly in monocytes and macrophages (76.7%) and lower signal originating from other leukocytes, such as neutrophils and lymphocytes (11.8% and 0.7%, P &lt;0.05 versus monocytes and macrophages). DNP colocalized with the myeloid cell marker CD11b on immunohistochemistry. PET/MRI revealed high uptake of 89 Zr-DNP in the aortic root of apolipoprotein E knock out (ApoE −/− ) mice (standard uptake value, ApoE −/− mice versus wild-type controls, 1.9±0.28 versus 1.3±0.03; P &lt;0.05), corroborated by ex vivo scintillation counting and autoradiography. Therapeutic silencing of the monocyte-recruiting receptor C-C chemokine receptor type 2 with short-interfering RNA decreased 89 Zr-DNP plaque signal ( P &lt;0.05) and inflammatory gene expression ( P &lt;0.05). Conclusions: Hybrid PET/MRI with a 13-nm DNP enables noninvasive assessment of inflammation in experimental atherosclerotic plaques and reports on therapeutic efficacy of anti-inflammatory therapy.
Decision Making Regarding Prophylactic Mastectomy: Stability of Preferences and the Impact of Anticipated Feelings of Regret
Authors: Sandra van Dijk, Mariëlle S. van Roosmalen, Wilma Otten, Peep F.M. Stalmeier
Journal: Journal of Clinical Oncology (2008)

Women who test positive for a BRCA1/2 mutation face difficult choices to manage their breast cancer risk; one of these choices is whether to opt for prophylactic mastectomy. Few data are available about this decision-making process. The current study provides data regarding the stability of risk-management preferences over time and the factors that are associated with these preferences.We analyzed data from 338 women who opted for breast cancer antigen (BRCA) testing. First, we prospectively assessed preferences of 80 BRCA mutation carriers at five different points in time ranging from 1 week after blood sampling up to 9 months after BRCA-test disclosure. Second, we applied univariate and multivariate regression analyses to examine which medical, sociodemographic, and psychological factors are related to a preference for prophylactic mastectomy.Ninety percent of the women already indicated a preference regarding risk management at baseline. Moreover, most women had stable preferences over time. Furthermore, anticipated feelings of regret in case of a hypothetical breast cancer diagnosis in the near future were strongly related to risk-management preference (odds ratio = 8.93; P < .0001).Women seem to decide at a relatively early stage about their risk-management preferences. Many of them may be sensitive to the possibility of regret in case of a bad outcome. We discuss whether possible regret in the future is a rational reason for opting for prophylactic mastectomy, or whether it signifies an emotional coping process or strategy in which the future costs are no longer fully considered.
DISCONTINUANCE OF COMPATIBILITY TEST IN SERUM TREATMENT
Authors: L. W. McGuire
Journal: JAMA (1918)

To the Editor:  —Numerous inquiries concerning compatibility tests, etc., have led us to offer the following suggestions for informal publication:  After consultation with reputable laboratory workers in Boston and New York, it was decided to discontinue the compatibility test of the donor's serum with the recipient's corpuscles. It would seem reasonable to believe that in all probability the donor's serum is so rapidly diffused and diluted in the blood stream that hemolysis and agglutination of a dangerous nature will not follow, whereas untoward reactions might result from introducing cells into a concentrated serum as in transfusion. Moreover, we have repeatedly given so-called incompatible serums to patients without the slightest untoward symptoms.  Further experience has led us to pool the serum from our donors. This simplifies the preparation and the administration of serum, and apparently gives more uniform results.  One of us, in a recent visit to New York, found physicians
The Mouse Cd1d-Restricted Repertoire Is Dominated by a Few Autoreactive T Cell Receptor Families
Authors: Se-Ho Park, Angela Weiss, Kamel Benlagha, Tim Kyin, Luc Teyton, Albert Bendelac
Journal: The Journal of Experimental Medicine (2001)

To define the phenotype and T cell receptor (TCR) repertoire of CD1d-dependent T cells, we compared the populations of T cells that persisted in major histocompatibility complex (MHC)-deficient mice, which lack mainstream T cells, with those from MHC/CD1d doubly deficient mice, which lack both mainstream and CD1d-dependent T cells. Surprisingly, up to 80% of the CD1d-dependent T cells were stained by tetramers of CD1d/α-galactosylceramide, which specifically identify the previously described CD1d autoreactive Vα14-Jα18/Vβ8 natural killer (NK) T cells. Furthermore, zooming in on the CD1d-dependent non-Vα14 T cells, we found that, like Vα14 NK T cells, they mainly expressed recurrent, CD1d autoreactive TCR families and had a natural memory phenotype. Thus, CD1d-restricted T cells differ profoundly from MHC-peptide–specific T cells by their predominant use of autoreactive and semiinvariant, rather than naive and diverse, TCRs. They more closely resemble other lineages of innate lymphocytes such as B-1 B cells, γδ T cells, and NK cells, which express invariant or semiinvariant autoreactive receptors. Finally, we demonstrate that the MHC-restricted TCR repertoire is essentially non–cross-reactive to CD1d. Altogether, these findings imply that lipid recognition by CD1d-restricted T cells may have largely evolved as an innate rather than an adaptive arm of the mouse immune system.
Binding of bacillus Calmette-Guérin-activated macrophages to tumor targets. Selective inhibition by membrane preparations from homologous and heterologous neoplastic cells.
Authors: P A Marino, C C Whisnant, D O Adams
Journal: The Journal of Experimental Medicine (1981)

The binding of tumor cells by activated macrophages is an initial and necessary event in the cytolysis of these targets. The data here indicate that membrane preparations from RL sigma 1 leukemia targets, EL-4 lymphoma targets, and P815 mastocytoma targets each inhibited binding of its homologous target to bacillus Calmette-Guérin (BCG)-activated murine macrophages in a dose-dependent fashion. Similar amounts of membrane from lymphocytes did not alter binding of the three neoplastic target to BCG-macrophages. Membranes of the three targets also inhibited binding of the heterologous neoplastic targets. Inhibitory activity of membrane preparations from P815, EL-4, and RL sigma 1 targets could be adsorbed by incubation of limiting concentrations of the membrane preparations with BCG-activated macrophages but not with thioglycollate broth-elicited macrophages. Exposure of BCG macrophages to membrane preparations from RL sigma 1, FL-4, or P815 targets inhibited subsequent cytolysis of the three targets. Inhibitory activity was increased in preparations enriched for plasma membrane. The data suggest that binding of three murine, nonadherent neoplastic targets to BCG-activated murine macrophages is mediated, in part, by recognition structures present within the plasma membranes of the three targets.
Genome-Wide Association Studies of Cancer
Authors: Zsofia K. Stadler, Peter Thom, Mark E. Robson, Jeffrey N. Weitzel, Noah D. Kauff, Karen E. Hurley, Vincent Devlin, Bert Gold, Robert J. Klein, Kenneth Offit
Journal: Journal of Clinical Oncology (2010)

Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited.
Television chef calls for minister of food to tackle obesity
Authors: A. O'Dowd
Journal: BMJ (2008)

The UK needs a minister for food to help tackle a growing obesity problem, the television chef Jamie Oliver has told MPs.

Mr Oliver, who was giving evidence to the parliamentary health select committee as part of its inquiry into health inequalities, said that the United Kingdom needs to make some profound changes in the next 10 years to tackle obesity and inequalities.

“Why isn’t there a minister for food?” he said. “Why isn’t there one person who comes from the private sector who is inspirational and all over the problem like a …
Human relevance of pre-clinical studies in stem cell therapy: systematic review and meta-analysis of large animal models of ischaemic heart disease
Authors: T. I. G. van der Spoel, S. J. Jansen of Lorkeers, P. Agostoni, E. van Belle, M. Gyongyosi, J. P. G. Sluijter, M. J. Cramer, P. A. Doevendans, S. A. J. Chamuleau
Journal: Cardiovascular Research (2011)

Stem cell therapy is a treatment strategy for ischaemic heart disease patients. Meta-analysis of randomized human trials showed <5% improvement in left ventricular ejection fraction (LVEF). Meta-analysis of available pre-clinical data of ischaemic heart disease could provide important clues to design human clinical trials. Random-effects meta-analysis was performed on pig, dog, or sheep studies investigating the effect of cardiac stem cell therapy in ischaemic cardiomyopathy (52 studies; n = 888 animals). Endpoints were LVEF and death. Ischaemia/reperfusion infarction was performed in 23 studies and chronic occlusion in 29 studies. Pooled analysis showed a LVEF difference of 7.5% at follow-up after cell therapy vs. control (95% confidence interval, 6.2–8.9%; P < 0.001). By exploratory multivariable meta-regression, significant predictors of LVEF improvement were: cell type [bone marrow mononuclear cells (BM-MNC) showed less effect than other cell types, e.g. mesenchymal stem cells; P = 0.040] and type of infarction (left anterior descending artery 8.0 vs. left circumflex artery 5.8%; P = 0.045). Cell therapy was not associated with increased mortality (P = 0.68). Sensitivity analysis showed trends towards more improvement with higher cell number (≥107), chronic occlusion models, and late injections (>1 week). After follow-up of 8 weeks, the effect of cell therapy decreased to 6%. This meta-analysis showed that large animal models are valid to predict the outcome of clinical trials. Our results showed that cell therapy is safe and leads to a preserved LVEF. Future trials should focus on cell types other than BM-MNC, large infarction, and strategies to obtain sustained effects.
SOME PROGNOSTIC CRITERIA FOR THE RESPONSE OF SCHIZOPHRENIC PATIENTS TO INSULIN TREATMENT
Authors: CONRAD WALL
Journal: American Journal of Psychiatry (1941)

A study was made of 37 schizophrenic patients in an attempt to discover factors related to their response to insulin shock treatment. Of good prognostic significance were found to be: 1. The presence of atypical schizophrenia. 2. The presence of considerable emotional reaction. 3. A history of some attempt at sexual adaptation. 4. Manifestation of sexual interest in the psychotic state. The patients who reacted poorly to the treatment 1. Very frequently came from a poorly integrated family with little solidarity among its members. 2. In many instances as children they were considered in some respect different from the other siblings. 3. They adapted to school in a somewhat worse than average fashion and showed a lack of ambition. 4. They showed very little sexual interest prior to the psychosis and there were no overt sexual manifestations other than autoeroticism during the psychosis. 5. Almost all of the patients who exhibited autistic behavior (mannerisms, grimacing, posturing, etc.) failed to respond. 6. They showed a picture of typical schizophrenia without extraneous admixtures.
Randomized Trial of a Shared Decision-Making Intervention Consisting of Trade-Offs and Individualized Treatment Information for <i>BRCA1/2</i> Mutation Carriers
Authors: M.S. van Roosmalen, P.F.M. Stalmeier, L.C.G. Verhoef, J.E.H.M. Hoekstra-Weebers, J.C. Oosterwijk, N. Hoogerbrugge, U. Moog, W.A.J. van Daal
Journal: Journal of Clinical Oncology (2004)

To evaluate a shared decision-making intervention (SDMI) for BRCA1/2 mutation carriers who have to make a choice between screening and prophylactic surgery for breasts and/or ovaries.The SDMI consisted of two value assessment sessions, using the time trade-off method, followed by individualized treatment information based on (quality-adjusted) life expectancy. After the baseline assessment (2 weeks after a positive DNA test result), women were randomly assigned to the SDMI group (n = 44), receiving the SDMI 2 months after the test result, or to the control group (n = 44). The short- and long-term effects, 3 and 9 months after the test result, were assessed using questionnaires. Data were collected on well-being, treatment choice, and decision-related outcomes.In the short term, the SDMI had no effect. In the long term, with respect to well-being, patients in the SDMI group had less intrusive thoughts (P =.05) and better general health (P =.01) and tended to be less depressed (P =.07). With respect to decision-related outcomes for the breasts, the SDMI group held stronger preferences (P =.02) and agreed more strongly to having weighed the pros and cons (P =.01). No effect was found on treatment choice. In the long term, interaction effects between the SDMI and cancer history were found. The SDMI showed an overall beneficial effect for unaffected women, whereas affected women tended to experience detrimental effects.We conclude that the SDMI improved decision making in unaffected BRCA1/2 mutation carriers. Supporting decision making in a systematic way using trade-offs is beneficial for these women.
Genome-Wide Transcript Profiling Reveals the Coevolution of Plastid Gene Sequences and Transcript Processing Pathways in the Fucoxanthin Dinoflagellate Karlodinium veneficum
Authors: Elisabeth Richardson, Richard G. Dorrell, Christopher J. Howe
Journal: Molecular Biology and Evolution (2014)

Plastids utilize a complex gene expression machinery, which has coevolved with the underlying genome sequence. Relatively, little is known about the genome-wide evolution of transcript processing in algal plastids that have undergone complex endosymbiotic events. We present the first genome-wide study of transcript processing in a plastid acquired through serial endosymbiosis, in the fucoxanthin-containing dinoflagellate Karlodinium veneficum. The fucoxanthin dinoflagellate plastid has an extremely divergent genome and utilizes two unusual transcript processing pathways, 3′-poly(U) tail addition and sequence editing, which were acquired following the serial endosymbiosis event. We demonstrate that poly(U) addition and sequence editing are widespread features across the Karl. veneficum plastid transcriptome, whereas other dinoflagellate plastid lineages that have arisen through independent serial endosymbiosis events do not utilize either RNA processing pathway. These pathways constrain the effects of divergent sequence evolution in fucoxanthin plastids, for example by correcting mutations in the genomic sequence that would otherwise be deleterious, and are specifically associated with transcripts that encode functional plastid proteins over transcripts of recently generated pseudogenes. These pathways may have additionally facilitated divergent evolution within the Karl. veneficum plastid. Transcript editing, for example, has contributed to the evolution of a novel C-terminal sequence extension on the Karl. veneficum AtpA protein. We furthermore provide the first complete sequence of an episomal minicircle in a fucoxanthin dinoflagellate plastid, which contains the dnaK gene, and gives rise to polyuridylylated and edited transcripts. Our results indicate that RNA processing in fucoxanthin dinoflagellate plastids is evolutionarily dynamic, coevolving with the underlying genome sequence.
Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice
Authors: Toshimasa Yamauchi, Yuichi Oike, Junji Kamon, Hironori Waki, Kajuro Komeda, Atsuko Tsuchida, Yukari Date, Meng-Xian Li, Hiroshi Miki, Yasuo Akanuma, Ryozo Nagai, Satoshi Kimura, Takeyori Saheki, Masamitsu Nakazato, Takeshi Naitoh, Kenichi Yamamura, Takashi Kadowaki
Journal: Nature Genetics (2002)
Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth.
Authors: P Lin, P Polverini, M Dewhirst, S Shan, P S Rao, K Peters
Journal: Journal of Clinical Investigation (1997)

Tie2 is a novel receptor tyrosine kinase that is expressed almost exclusively by vascular endothelium. Disruption of Tie2 function in transgenic mice resulted in embryonic lethality secondary to characteristic vascular defects; similar defects occurred after disruption of the Tie2 ligand. These findings indicate that the Tie2/Tie2 ligand pathway plays important roles during development of the embryonic vasculature. To determine whether the Tie2 pathway was involved in pathologic angiogenesis in adult tissues, a soluble form of the extracellular domain of murine Tie2 (ExTek.6His) was developed and used as a Tie2 inhibitor. After a single application of the ExTek.6His protein into a rat cutaneous window chamber, growth of a mammary tumor inside the chamber was reduced by > 75% (P < 0.005), and tumor vascular length density was reduced by 40% when compared with control-treated tumors (P < 0.01). In the rat cornea, ExTek.6His blocked angiogenesis stimulated by tumor cell conditioned media. ExTek.6His protein did not affect the viability of cultured tumor cells, indicating that the antitumor effect of ExTek.6His was due to the inhibition of tumor angiogenesis. These data demonstrate a role for the Tie2 pathway in pathologic angiogenesis, suggesting that targeting this pathway may yield effective antiangiogenic agents for treatment of cancer and other angiogenic diseases.
Confounding by Indication and the Risk of Hyperlipidemia in Observational Studies of Antipsychotics
Authors: FERNANDO RICO-VILLADEMOROS, ELENA P. CALANDRE
Journal: American Journal of Psychiatry (2007)

a strong case in favor of making catatonia a separate category in subsequent editions of the DSM.However, their assertion that the diagnosis of catatonia should be made by observing the patient's response to the administration of lorazepam/amobarbital seems to be an oversimplification of the issue.It is correct that catatonic features have been shown to respond to the administration of these compounds.However, the assumption that "[t]he diagnosis may be confirmed by symptomatic improvement after the acute administration of a challenge dose of lorazepam or amobarbital" (1, p. 1875) seems to be an overgeneralization.Response to these agents by no means provides a definitive diagnosis of catatonia, and there is no evidence to support the use of these tests as confirmatory.Catatonic features are not specific to any one condition and can be observed in a variety of conditions.Some of these conditions might respond to lorazepam or amobarbital; for example, conversion disorders such as conversion mutism are associated with features that do resemble catatonia and do respond to the amobarbital assisted interview.In summary, it may be prudent to avoid the use of response to lorazepam/amobarbital as a confirmatory test for the presence of catatonia.
Leprosy Cases in the British Isles
Authors: L. Rogers, J. H. Cook, E. Muir
Journal: BMJ (1940)

ETHDEAL BRUTRSAL IAs this procedure has not been carried out in clinical patients, and as the dose required to heparinize a dog differs from that required to heparinize a patient, it is difficult to predict the dosage accurately.From OUr experience we would suggest that between 15 and 20 units per kg./hr.should be adequate.Since continuouLs intra- venous administration is impracticable in patients outside hospitals, the intermittent intravenous injection of the heparin in doses of 1,500 units q.h. for the patient of average weight should suffice.Consideration of this experimental evidence sLuggests that it might be possible to insert glass cannulae in torn P.~~~~A FIG.2.-Approxnimately half actual size.arteries soon after the accident.With suitable doses of heparin the cannulae might be kept patent until the patient could be removed to a hospital where repair of the vessels could be undertaken.This might be carried out with the simplest technique in advanced dressing stations behind the fighting line.In this way some of the disastrous effects of acute failure of circulation in extremities and neck might be prevented. SummaryWith a view to using glass cannulae to bridge defects in the arterial system of human beings as a temporary measure a series of experiments have been carried out on dogs.The results have been tabulated.With adequate heparinization, using a pump to provide continuous intravenous administra- tion.glass cannulae of 1.5 to 2 mm.bore and 3.5 cm.length may be kept free from clot for varying periods of time up to seventy-six hours.The danger of oozing from the operatixe field in overdosage with heparin must be borne in mind.
Membrane‐Directed High Bactericidal Activity of (Gold Nanoparticle)–Polythiophene Composite for Niche Applications Against Pathogenic Bacteria
Authors: Manab Deb Adhikari, Sudeep Goswami, Biswa Ranjan Panda, Arun Chattopadhyay, Aiyagari Ramesh
Journal: Advanced Healthcare Materials (2012)

Abstract The use of nanoscale materials as bactericidal agents represents a novel paradigm in the development of therapeutics against drug‐resistant pathogenic bacteria. In this paper the antimicrobial activity of a water soluble (gold nanoparticle)–polythiophene (AuNP‐PTh) composite against common bacterial pathogens is reported. The nanocomposite is broad‐spectrum in its bactericidal activity and exhibits a membrane‐directed mode of action on target pathogens. The therapeutic potency of AuNP‐PTh is demonstrated by experiments which reveal that the nanocomposite can breach the outer membrane defense barrier of Gram‐negative pathogens for subsequent killing by a hydrophobic antibiotic, inhibit the growth of model gastrointestinal pathogens in simulated gastric fluid, and significantly eradicate bacterial biofilms. The high bacterial selectivity and lack of cytotoxicity on human cells augers well for future therapeutic application of the nanocomposite against clinically relevant pathogenic bacteria.