tbuckley/cabot-search huggingface dataset:
Abstract LB-508: A GSA-NMP1 conjugate: An NIR-activatable fluorescence imaging agent to detect peritoneal ovarian cancer metastases
Authors: Vinita M. Alexander, Kohei Sano, Zhanqian Yu, Takahito Nakajima, Peter L. Choyke, Marcin Ptaszek, Hisataka Kobayashi
Journal: Cancer Research (2012)

Abstract Purpose: There is a need to improve detection of peritoneal ovarian cancer metastases before and during surgery. Previous designs of activatable GSA-fluorophore probes, which target lectin receptors, have used only visible range dyes conjugated to GSA. However, activatable agents emitting fluorescence in the NIR range are advantageous because NIR photons have deeper in vivo tissue penetration and lower background autofluorescence than those emitting in the visible range. An NIR-activatable GSA fluorophore pair can be synthesized using the dye NMP1. This NMP1 dye has two unique absorption peaks (in green and NIR wavelength ranges) with a single NIR emission peak of 780nm. NMP1 thus has two different Stoke's shifts that have the potential to allow separate imaging of tumor nodules both at the surface and at depths below the surface. Experimental Design: GSA was conjugated with 2 NMP1 molecules to create a self-quenching complex (GSA-NMP1). The activation magnitude of GSA-NMP1 was validated by adding 10% SDS. Flow cytometry, fluorescence microscopy, and in vivo spectral fluorescence imaging were carried out to compare GSA-NMP1 with GSA-IR800 (an always on control agent with similar emission to NMP1) in terms of intracellular activation and abilities to allow detection of small ovarian cancer implants in mice models. Sensitivity and specificity of GSA-NMP1 for implant detection were determined by co-localizing NMP1 emission spectra with red fluorescent protein expressed constitutively in SHIN3 tumor implants. Image processing in Java was used to subtract spectral images, with resulting images theorized to show tumor nodules at a depth below the surface. Results: The fluorescence signal of GSA-NMP1 can be activated ∼100-fold and was specifically yielded after internalization into SHIN3 cells 3h after incubation. Submillimeter ovarian cancer implants in the peritoneal cavity were clearly detectable in vivo with spectral fluorescence imaging. Among 555 peritoneal lesions, the sensitivity and specificity for GSA-NMP using NIR and green excitation light, were 75%/92% and 91%/92% for lesions ∼0.8 mm or greater in diameter, respectively. Image processing suggests that nodules at a depth below the small bowel are imaged only with GSA-NMP1 by subtraction of the two excitation images. Conclusions: GSA-NMP1 is useful in imaging peritoneal ovarian cancer metastases, located both superficially and deep in the abdominal cavity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-508. doi:1538-7445.AM2012-LB-508
Criminal Recidivism and Psychiatric Illness
Authors: SAMUEL B. GUZE, DONALD W. GOODWIN, J. BRUCE CRANE
Journal: American Journal of Psychiatry (1970)

The authors describe a study of criminal recidivism during an eight- to nine-year period; it indicated that increased recidivism rates were associated with the following factors: "flat-timer" status (reflecting a more extensive criminal career), relative youth, and diagnoses of sociopathy, alcoholism, and drug dependency. Remission of the latter two conditions was correlated with a decline of recidivism.
Immunoprotective Leishmania major synthetic T cell epitopes.
Authors: A Jardim, J Alexander, H S Teh, D Ou, R W Olafson
Journal: The Journal of Experimental Medicine (1990)

Using the predictive algorithm of Rothbard and Taylor (1988. EMBO J. 7:93) and the primary structure of gp63 (Button, L., and M.R. McMaster. 1988. J. Exp. Med. 167:724; Miller, R.A., S.G. Reed, and M. Parsons. 1990. Mol. Biochem. Parasitol. 39:267) we have been able to delineate the structures of a number of gp63 T-cell epitopes which stimulate the proliferation of CD4+ cells. One of these synthetic antigens, inoculated subcutaneously with adjuvant, was shown to specifically induce proliferation of the Th1 subset and provided immunoprotection against two species of Leishmania parasites.
Ethical Dilemmas in Providing Health Care to Workers
Authors: LINDA ROSENSTOCK
Journal: Annals of Internal Medicine (1987)

The internist, expected to play an increasing role in occupational medicine, is likely to encounter ethical dilemmas in treating working patients, including those involving loyalty, confidentiality, reporting known or suspected occupational hazards and diseases, and maintaining awareness about occupational health factors. Many of these dilemmas become realized when the internist integrates occupational health services into general internal medicine practice, particularly when these services are important to employment decisions, such as the preemployment and periodic examinations. Appropriate responses to these dilemmas and the situations from which they arise can be formulated, based on accepted ethical and legal principles.
Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma
Authors: E K Mai, U Bertsch, J Dürig, C Kunz, M Haenel, I W Blau, M Munder, A Jauch, B Schurich, T Hielscher, M Merz, B Huegle-Doerr, A Seckinger, D Hose, J Hillengass, M S Raab, K Neben, H-W Lindemann, M Zeis, C Gerecke, I G H Schmidt-Wolf, K Weisel, C Scheid, H Salwender, H Goldschmidt
Journal: Leukemia (2015)
Abstract A6: Cancer-associated fibroblasts (CAF) expressing CD44 high increased the aggressiveness of cancer cells
Authors: Seon-Hui Shim, J. Hun Hah, Myung-Whun Sung
Journal: Clinical Cancer Research (2010)

Abstract Cancer-associated fibroblast (CAF) is considered of one of the most important factors influencing tumor microenvironment. CD44 is known to a marker of head and neck cancer stem cell and is a glycoprotein involved in cell-cell interactions, cell adhesion and migration. Tissues from several head and neck cancer patients were gathered and fibroblasts from tumor tissues and normal tissues away from cancer were isolated. We found CAF overexpressed CD44 when compared to normal part of fibroblast, thus investigated the role of CAF which is overexpressing CD44. Cancer cells which are co-cultured with CAF migrated better than normal fibroblast when wound assay were performed. To test whether this motility of cancer is related to CD44 on CAF, CAF was inhibited by neutralizing antibody of CD44. After treatment with neutralizing antibody, the motility of cancer cells reduced. To confirm that CAF influences tumor cell migration, mixture of CAF and cancer cells were laid on an upper well, then these cells would travel 3D environment which is made by our own idea. Cancer cells which get ability to migrate and can form colonies can survive on the bottom well. When treated neutralizing antibody, cells could neither migrate nor make colonies well than antibody-free mixture. In conclusion, CAF influenced cancer cell migration through the CD44. If CD44 on CAF was blocked, the movement and aggressiveness of cancer cells weakened. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A6.
Using drugs safely
Authors: S. Maxwell
Journal: BMJ (2002)

The recent Audit Commission report A Spoonful of Sugar was grim reading.1 The report suggested that nearly 1100 people died last year in England and Wales as a result of medication errors or adverse reactions to medicines and that the number had increased fivefold in just 10 years. This alarming increase may be an overestimate inflated by changes in defining and reporting causes of death and cannot all be attributed to a true deterioration in prescribing. However, studies elsewhere also hint at high rates, 2 3 although the definitions and data have been questioned.3 The Audit Commission failed to distinguish clearly between medication errors, inevitable adverse reactions, and potentially preventable adverse reactions. Since strategies for minimising each are different, we need data that tell us where problems lie.

There are several reasons why drug errors might have risen (see box). In addition, human error is most likely when inexperienced and overworked staff, in a stressful environment, struggle with unfamiliar …
Excess benign melanocytic naevi.
Authors: B. Hughes, C. C. Bailey
Journal: BMJ (1989)

<h3>Abstract</h3> <h3>Background and Objective</h3> Cryo-electron tomography (cryo-ET) is an imaging technique that enables 3D visualization of the native cellular environment at sub-nanometer resolution, providing unpreceded insights into the molecular organization of cells. However, cryo-electron tomograms suffer from low signal-to-noise ratios and anisotropic resolution, which makes subsequent image analysis challenging. In particular, the automated detection of membrane-embedded proteins is a problem still lacking satisfactory solutions. <h3>Methods</h3> We present MemBrain – a new deep learning-based pipeline that automatically detects membrane-bound protein complexes in cryo-electron tomograms. After subvolumes are sampled along a segmented membrane, each subvolume is assigned a score using a convolutional neural network (CNN), and protein positions are extracted by a clustering algorithm. Incorporating rotational subvolume normalization and using a tiny receptive field simplify the task of protein detection and thus facilitate the network training. <h3>Results</h3> MemBrain requires only a small quantity of training labels and achieves excellent performance with only a single annotated membrane (F1 score: 0.88). A detailed evaluation shows that our fully trained pipeline outperforms existing classical computer vision-based and CNN-based approaches by a large margin (F1 score: 0.92 vs. max. 0.63). Furthermore, in addition to protein center positions, MemBrain can determine protein orientations, which has not been implemented by any existing CNN-based method to date. We also show that a pre-trained MemBrain program generalizes to tomograms acquired using different cryo-ET methods and depicting different types of cells. <h3>Conclusions</h3> MemBrain is a powerful and label-efficient tool for the detection of membrane protein complexes in cryo-ET data, with the potential to be used in a wide range of biological studies. It is generalizable to various kinds of tomograms, making it possible to use pretrained models for different tasks. Its efficiency in terms of required annotations also allows rapid training and fine-tuning of models. The corresponding code, pretrained models, and instructions for operating the MemBrain program can be found at: https://github.com/CellArchLab/MemBrain
Can the Dutch Government really be abandoning smokers to their fate?
Authors: Deborah Arnott, Florence Berteletti, John Britton, Antonella Cardone, Luke Clancy, Lorraine Craig, Geoffrey T Fong, Stanton A Glantz, Luk Joossens, Michel T Rudolphie, Michael R Rutgers, Sidney C Smith, Hans Stam, Robert West, Marc C Willemsen
Journal: The Lancet (2011)
DIPHTHERIA OF THE PENIS
Authors: MAXWELL P. BOROVSKY
Journal: JAMA (1935)

Diphtheria of the penis is a rare disease. A careful review of the literature reveals none reported at as early an age as my patient. In 1930 Hoyne and Levy,<sup>1</sup>in reporting a case of diphtheria of the penis in a 7 year old boy, reviewed the literature, which disclosed only fifteen similar reports. The first cases of diphtheria of the penis were reported in 1897 and, strangely enough, by three different observers in a period of a few months. Munn,<sup>2</sup>in February 1897, reported three cases of this disease. One was in a 5 year old boy who developed the condition following circumcision. There were no cultures taken, and diphtheria antitoxin was not administered. The infection cleared up under local treatment. Another was in a 9 months old infant who was circumcised, following which a membrane developed at the site of operation which on culture showed Klebs-Loeffler
Hypoxia-inducible transcription factor 2α promotes steatohepatitis through augmenting lipid accumulation, inflammation, and fibrosis
Authors: Aijuan Qu, Matthew Taylor, Xiang Xue, Tsutomu Matsubara, Daniel Metzger, Pierre Chambon, Frank J. Gonzalez, Yatrik M. Shah
Journal: Hepatology (2011)

Oxygen dynamics in the liver is a central signaling mediator controlling hepatic homeostasis, and dysregulation of cellular oxygen is associated with liver injury. Moreover, the transcription factor relaying changes in cellular oxygen levels, hypoxia-inducible factor (HIF), is critical in liver metabolism, and sustained increase in HIF signaling can lead to spontaneous steatosis, inflammation, and liver tumorigenesis. However, the direct responses and genetic networks regulated by HIFs in the liver are unclear. To help define the HIF signal-transduction pathway, an animal model of HIF overexpression was generated and characterized. In this model, overexpression was achieved by Von Hippel-Lindau (Vhl) disruption in a liver-specific temporal fashion. Acute disruption of Vhl induced hepatic lipid accumulation in an HIF-2α-dependent manner. In addition, HIF-2α activation rapidly increased liver inflammation and fibrosis, demonstrating that steatosis and inflammation are primary responses of the liver to hypoxia. To identify downstream effectors, a global microarray expression analysis was performed using livers lacking Vhl for 24 hours and 2 weeks, revealing a time-dependent effect of HIF on gene expression. Increase in genes involved in fatty acid synthesis were followed by an increase in fatty acid uptake-associated genes, and an inhibition of fatty acid β-oxidation. A rapid increase in proinflammatory cytokines and fibrogenic gene expression was also observed. In vivo chromatin immunoprecipitation assays revealed novel direct targets of HIF signaling that may contribute to hypoxia-mediated steatosis and inflammation.These data suggest that HIF-2α is a critical mediator in the progression from clinically manageable steatosis to more severe steatohepatitis and liver cancer, and may be a potential therapeutic target.
Simultaneous measurement of pulmonary venous flow by intravascular catheter Doppler velocimetry and transesophageal doppler echocardiography: Relation to left atrial pressure and left atrial and left ventricular function
Authors: Thomas Hofmann, Andreas Keck, Gerit Van Ingen, Ognjen Simic, Jörg Ostermeyer, Thomas Meinertz
Journal: Journal of the American College of Cardiology (1995)
Guilty of loving the NHS
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2010)

Last month I visited Boston in the United States, and in particular the Beth Israel Deaconess Hospital. On a sample of one, it struck me that healthcare for those served by the US health system and for those who work in it is vastly different to the UK experience. A sense of calm and dignity pervaded the hospital. Staff, and even patients, smiled as you passed them on corridors and in lifts. A harpist strummed soothing melodies, and ‘public safety officers’ lurked discreetly in case the harpist's notes failed to keep the peace.

A visitor might easily fall in love with US healthcare. But then the US system struggles to match UK health outcomes on around double the per capita spend. The US health system is ranked 50th for life expectancy and scores low on some measures of responsiveness and quality of healthcare. Just under 50 million people are uninsured and find healthcare hard to access. This blot on US healthcare's landscape is its most visible.

US healthcare, then, is a story of success and failure travelling hand in hand. The success stories are instructive for health systems everywhere, indeed the obsession of UK health leaders for over a decade has been to seek guidance from their US counterparts. But the failures are an equally potent warning, a lesson in how not to do it. This month's issue carries several pieces comparing the US and UK approaches to disparities in healthcare – and healthcare more broadly.

Just as economic arguments are now driving our healthcare agenda and further restructuring, the US debate is driven by economics. Should the state really bear the cost of universal coverage? While the UK's decision and passion has been that it should, the US has traditionally taken the opposite view. President Obama has now lurched towards better healthcare for the uninsured, a seismic shift in the US health system, and a legacy policy that will dominate history lessons about his presidency.

Now the US debate has become even more passionate with Republicans defending the American Way to the last sharp intake of breath. It is in this political firestorm that a Harvard professor has become the focus of furious debate. Don Berwick, paediatrician and head of the Institute of Healthcare Improvement, is Obama's nominated head of the Centers of Medicare and Medicaid Services, a role that will be influential in US health reform.

It is hard to criticize Berwick as a doctor, leader or champion of quality improvement. Yet Berwick has become a target for Republicans opposed to Obama's reforms. And Berwick's sin is a simple one: he once declared his love, albeit reservedly, for the NHS. Naughty man, I hear he also enjoys tea.
Reviews, Notes, and Listings: Color Atlas of Diabetes
Authors: Robert Spanheimer
Journal: Annals of Internal Medicine (1993)

Literature of Medicine15 January 1993Reviews, Notes, and Listings: Color Atlas of DiabetesRobert Spanheimer, MDRobert Spanheimer, MDUniversity of Iowa Hospitals and Clinics, Iowa City, IA 52246.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-2-199301150-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Color Atlas of DiabetesSecond edition. Arnold Bloom and John Ireland. 137 pages. St. Louis, Missouri: Mosby Year Book, Inc.; 1992. $59.95.Caring for diabetic patients is a time-intensive undertaking because of the acute metabolic complications and the chronic complications that may involve any organ in the body. The idea behind the graphic presentation of the clinical and histologic manifestations of diabetes is that a picture is worth a thousand words (or the time involved in reading that much). Strong sections of the book include histologic sections of diabetic pancreas and kidney that help visualize the pathologic process resulting in the clinical ... Author, Article, and Disclosure InformationAffiliations: University of Iowa Hospitals and Clinics, Iowa City, IA 52246. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 January 1993Volume 118, Issue 2Page: 160KeywordsChildrenCirrhosisConnective tissueEye diseasesKidneysPancreasPheochromocytomaTwinsUlcers ePublished: 15 August 2000 Issue Published: 15 January 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Angiotensin II provokes cesium-induced ventricular tachyarrhythmias
Authors: N Gondo
Journal: Cardiovascular Research (2001)

The purpose of this study was to investigate whether angiotensin II provokes ventricular tachyarrhythmias and to clarify its mechanism using the cesium-induced arrhythmia model, which has been widely used as an afterdepolarization and triggered activity model.Eighteen adult mongrel dogs of either sex weighing 9.6-23.0 kg were studied. The dogs were randomly divided into three groups. In the control group (n=6), the subjects received intravenous saline solution at a 0.45 ml/kg/h, and intravenous bolus injections of cesium (0.25, 0.5, 1.0 mmol/kg) were given at 20-min intervals. In the captopril-treated group (n=6), captopril was administered intravenously at 15 microg/kg/min, and cesium was injected as above. After the infusion of only captopril, in the captopril-treated group, angiotensin II was simultaneously infused at a dose of 0.1 ng/kg/min, and cesium was injected as above. When the dog survived, the dose of angiotensin II was increased to 1.0 ng/kg/min, and the same procedure was repeated. The remaining six dogs were simultaneously infused with captopril (15 microg/kg/min), angiotensin II (1.0 ng/kg/min), and U-73122 (10 microg/kg/min), a selective phospholipase C blocker, and injected with cesium (1.0 mmol/kg). Forty minutes after termination of U-73122 infusion, the dogs were injected with the same dose of cesium.Sustained ventricular tachycardia or ventricular fibrillation was induced by cesium in all of the dogs in the control group. In the captopril-treated group, none of the dogs showed these arrhythmias when only captopril was infused. The treatment of captopril significantly reduced lethal arrhythmias (P<0.01 vs. control group). During the simultaneous infusion of captopril and angiotensin II (0.1 ng/kg/min), cesium produced sustained ventricular tachycardia in all six dogs and the arrhythmia developed into ventricular fibrillation in three dogs. By increasing the dose of angiotensin II (1.0 ng/kg/min), the surviving three dogs died following induced ventricular fibrillation. The additional infusion of angiotensin II (0.1 and 1.0 ng/kg/min) significantly increased fatal arrhythmias (P<0.01 vs. only captopril- infused period, respectively). None of the dogs in the third group exhibited ventricular tachycardia during the infusion of U-73122, and ventricular fibrillations were recorded in all six dogs in the absence of U-73122. The treatment of U-73122 significantly reduced lethal arrhythmias. (P<0.01 vs. control period).These results suggest that angiotensin II provokes cesium-induced ventricular tachyarrhythmias by increasing calcium release from sarcoplasmic reticulum in myocytes via activation of a phosphatidylinositol response.
Effects of tetrodotoxin, lidocaine, verapamil, and AHR-2666 on Ouabain-induced delayed afterdepolarizations in canine Purkinje fibers.
Authors: M R Rosen, P Danilo
Journal: Circulation Research (1980)

We used standard microelectrode techniques to record delayed afterdepolarizations (DAD) induced by ouabain (2 x 1 0 7 M) in isolated canine Purkinje fibers (PF) and studied the response of DAD to the fast Na* channel blocker, tetrodotoxin (TTX, 1 mg/liter); the slow channel blocker, verapamil (verap, 1 mg/liter); the putative Ca 2+ blocker, AHR-2666 (AHR, 45 mg/liter); and lidocaine (lido, 4 mg/liter), which increases steady state outward current and decreases background inward current.PF were driven at cycle lengths of 1000-200 msec.Ouabain superfusion for 30 minutes induced DAD with amplitudes of 17.0 ± 1.5 (mean ± SE) mV at a cycle length of 200 msec.TTX, verap, AHR, and lido all depressed DAD amplitude (P < 0.05).To intercompare the effects of the drugs, graphs were constructed relating DAD amplitude to basic cycle length, and the relative magnitude of effects of the drugs on DAD amplitude at all cycle lengths was tested using a nested analysis of variance.The effects of verap and AHR were equivalent, and both decreased DAD amplitude more at short (to 37% of ouabain control) than at long (to 76%) cycle lengths (P< 0.05).Lido had a different effect and decreased DAD nearly equivalently at short (to 64%) and long (to 75%) cycle lengths.The actions of TTX were intermediate between-and significantly different from-those of the other drugs (P < 0.05).AHR and verap appear to act similarly, by modifying the current responsible for DAD, whereas lido appears to act by a different mechanism, perhaps by increasing steady state outward current.The actions of TTX may be a result of its effect on the transient inward current or on a background current carried by Na * .