tbuckley/cabot-search huggingface dataset:
Abstract B17: Inhibition of lung tumor progression in a metastatic mouse model following intravenous delivery of siRNA nanocomplexes
Authors: Jason G. Fewell, Khursheed Anwer, Kevin Polach, Majed Matar, Jennifer Rice, Angela Rea-Ramsey, Jeff Sparks, Diane McClure, Casey Pence, Elaine Brunhoeber, Leslie Wilkinson
Journal: Cancer Research (2012)

Abstract Exploiting the RNAi pathway offers the potential to advance the treatment of many diseases through highly specific and efficient silencing of gene products. Unfortunately, the requisite safe and efficient delivery of nucleic acids to target cells remains a fundamental problem for the development of RNA and DNA based therapeutics. We have developed a versatile lipopolyamine based delivery system that has been optimized for in vivo delivery by incorporating functional groups onto the core cationic lipopolyamine structure. The direct modification of the core structure (named Staramine) allows for the generation of nanoparticle formulations with a wide range of physicochemical properties and does not require the co-formulation of commercial helper or pegylated lipids. We have previously reported safe, efficient and persistent siRNA mediated transcript knockdown specifically in the lung endothelium using the Starmaine delivery system. Here we extend those observations by administering a siRNA that targets vascular endothelial growth factor receptor 2 (VEGFR-2; KDR/Flk-1) in an animal model of metastatic lung cancer. VEGFR-2, a receptor tyrosine kinase, has been shown to be mainly expressed on endothelial cells and plays a critical role in cell proliferation and differentiation and consequently is also important in angiogenesis associated tumor growth and metastasis. Repeated intravenous administration of nanocomplexes comprised of Staramine formulated VEGFR-2 siRNA (~2 mg/kg/dose) resulted in a significant (40%) reduction of VEGFR-2 transcript levels in isolated tumors from the lungs of mice compared to control injected animals. Similar levels of transcript knockdown were not achieved in tumors when using siRNAs against targets not having the high level of endothelial cell restriction that is seen with VEGFR-2. Immunohistopathology of the lungs of tumor bearing mice administered VEGFR-2 siRNA indicated a significant decrease in vascular density in lung tumors and was consistent with an overall reduction in tumor burden in the mouse lungs. These results support the continued evaluation of using Staramine to deliver siRNAs and other similar molecules as potential therapies for diseases of the lung where the vascular endothelium may be involved. Citation Format: Jason G. Fewell, Khursheed Anwer, Kevin Polach, Majed Matar, Jennifer Rice, Angela Rea-Ramsey, Jeff Sparks, Diane McClure, Casey Pence, Elaine Brunhoeber, Leslie Wilkinson. Inhibition of lung tumor progression in a metastatic mouse model following intravenous delivery of siRNA nanocomplexes [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr B17.
Allocating development assistance for health
Authors: Benjamin P C Brooks, Joseph L Dieleman, Annie Haakenstad, Michael Hanlon
Journal: The Lancet Global Health (2014)

BackgroundIn the past decade, development assistance for health (DAH) distributed to developing countries grew at an annual rate of 11·6%, to a total of US$31·3 billion in 2013. Although this substantial rise in DAH is well documented, little has been done to quantify the determinants of its allocation.MethodsWe derived estimates of total DAH received by recipient country during 5 year intervals from 1990–2010 from data published in the Institute for Health Metrics and Evaluation's Financing Global Health 2012 report. Disease burden information during the same period was available from the Global Burden of Disease Study 2010. Other country-level characteristics that might affect the allocation of aid, such as gross domestic product and quality of governance, were also included. We use linear regression to identify patterns that typify how DAH is allocated across countries and time.FindingsIncome is associated with the allocation of DAH across countries but not across time, meaning that donors provide more health aid for low-income countries than for high-income countries, but an increase in a country's wealth with time does not mean it will receive less aid. Countries that are democratic and have civil or political rights receive more aid. Regarding disease burden, countries with a larger disease burden receive more DAH. A 10% increase in disease burden is associated with a 6% increase in DAH. Unlike gross domestic product, changes in disease burden within a country, over time, do affect DAH allocation; this is especially true for transparent and democratic countries. In these countries, a 10% increase in burden (which might be caused by disease epidemic or rising population) would result in up to a 30% increase in DAH. Lastly, DAH allocation is especially responsive to a recipient country's burden of HIV/AIDS.InterpretationThis analysis provides evidence that donors give less to high-income countries and more to democracies with increased disease burdens. However, when disease burden is examined in greater detail, the emergence of HIV/AIDS as a primary driver of aid allocation is interesting in view of the diverse set of priorities within the global health agenda. With the growth of DAH slowing due to the economic crisis and an increasing number of non-state organisations operating in global health, knowledge of which factors affect resource allocation at the aggregate level can inform discussions about whether resources are being distributed appropriately.FundingThe Bill & Melinda Gates Foundation.
THE EFFECT OF DAYLIGHT AND DRYING ON THE HUMAN AND BOVINE TYPES OF TUBERCLE BACILLI
Authors: L. Findlay, W. B. M. Martin
Journal: BMJ (1915)

EFFECT OF DAYLIGHT AND DRYING ON TIJBERCLE BACILLI.-TJAN.T6, 1915 height slight ptosis of the left upper lid manifested itself, and tllis feature, it was particularly notice(l, became more marhed wh1eni the patient was apprehensive or suffering from menital excitemenit, as, for instaice, wvhea the ideea of operative easuires as suggested to her at thie conisultation.Shle was last seenl in October and conl)plained tlheni of occa- sioimal attacks of blurred visioIn, mllore mllarlkel oni getting ouit of b)e(d ini the morniing or whien eniteringt a brightly lighlted room.SIhe experienicedino difficulty in near wvork or movilng about ontloors or in the house.Slhe still stuffers at tinmes from pain (lownl the riglht ;icide of the neclk, aggravated wlhen the bea(l is tturned suddelyly to the right.Has no diplopia, butt occasionally stumbles.The eyes slhow equial but (lilate(d pupils, wlich react feebly to light but fairly to accommodation anid convergence.Slight jerky nystagmius can still be elicitedi, otlherwise the ocular mi-ovemenits are ftull and free; there is no squinit or ptosis.The left disc is still hyperaemic, its edge blurre(d but letiniable, exudatioin covers the vessels in places but does not seem to cause any suddenl diminutioin, although they as a whole seem narrowe(l.A less marked conidition is present in the right disc, anid in ad(ldition are two patchles of exudationl, one above to the niasal si(le and onie below.The vision in both is -5 and J. 1, the visual fields uncontracted, hut the central scotoma remains about the same size.
Lack of Splenic Uptake of In-111 Pentetreotide Due to Splenic Embolization
Authors: Yang Lu, Eileen M. O’Reilly, Jorge A. Carrasquillo
Journal: Clinical Nuclear Medicine (2009)

We report an incidental finding of absent splenic uptake of indium-111 pentetreotide in a patient with unresectable pancreatic neuroendocrine carcinoma, who underwent splenic embolization for bleeding varices, and to debulk a 17.9 by 8.5 cm mass with retroperitoneal extension. Spleen infarction was confirmed on a dedicated contrast enhanced computed tomography (CT).
Acts and omissions, killing and letting die.
Authors: R Gillon
Journal: BMJ (1986)

Gillon asks what, if any, moral importance resides in the distinction between killing and letting die in the context of medical care. He considers and rejects the acts and omissions doctrine, which claims that actions (killing) resulting in some undesirable end are in general morally worse than failures to act (allowing to die) that have the same result. He also refutes the argument that the moral distinction between killing and letting die is one of harming versus benefitting, and that a physician has a responsibility not to harm (kill) a patient but no duty to help (keep alive). Gillon concludes by discussing the moral claims upon which the Roman Catholic rejection of the acts and omissions doctrine is based, which are the subjects of his next British Medical Journal article on medical ethics.
Inhibition of bone resorption blunts osteoarthritis in mice with high bone remodelling
Authors: A. Kadri, T. Funck-Brentano, H. Lin, H.-K. Ea, D. Hannouche, C. Marty, F. Liote, V. Geoffroy, M. E. Cohen-Solal
Journal: Annals of the Rheumatic Diseases (2010)

Background Osteoarthritis (OA) is characterised by cartilage degradation and bone lesions. Subchondral bone may be involved in the pathogenesis of cartilage matrix breakdown. Objective To assess the role of bone remodelling in OA by studying the effect of bisphosphonate on OA development in mice with high bone remodelling. Methods Mice overexpressing Runx2 (Runx2-Tg) under the control of collagen type I that displayed high bone remodelling were used. Joint instability was performed by partial medial meniscectomy to induce OA. Results Six weeks after surgery, tibial cartilage of Runx2-Tg mice displayed an increased number of ADAMTS-4- and ADAMTS-5-expressing chondrocytes compared with controls (p<0.05). This increase was higher in Runx2-Tg mice than in wild-type mice, although their OA score did not differ (2.5±0.6 vs 2.4±0.2, P=NS). Pamidronate reduced the OA score in Runx2-Tg mice but not in wild-type littermates (1.2±0.5 vs 2.7±0.4; p<0.05) despite the reduction of bone resorption and of the expression of cartilage proteases in both genotypes. Conclusions These findings support the hypothesis that the level of bone resorption influences cartilage metabolism and that inhibition might prevent the progression of OA. Targeting bone resorption might therefore provide an approach to the treatment of high bone resorbing forms of OA.
Abstract 1264: Extracellular galectin-3 induces tumor-specific apoptosis through the interaction with highly glycosylated cell surface β1 integrin
Authors: Sok-Hyong Lee, Abussamad Zerrouqi, Saroja Devi, Erwin G. Van Meir
Journal: Cancer Research (2010)

Abstract Galectins are a family of animal lectins, which bind beta-galactose moieties. Gal3 is the only chimeric family member of Gals and consists of a collagen-like N-terminal region and a C-terminal carbohydrate recognition domain (CRD), which has binding affinity for galactose and N-acetyl-lactosamine. Gal3 is known to be secreted through Golgi apparatus-independent alternative pathway. Previously, we found that stimuli-induced p53 activation induced bystander killing effect against adjacent cells. This p53 bystander effect is mediated through the secretion of Gal3 with the requirement of p53-dependent induction of tumor suppressor activated pathway-6 (TSAP6). We found the apoptotic activity of extracellular Gal3: a variety of tumor cell types (malignant glioma, breast, colon, prostate, lung) are sensitive to Gal3-mediated killing, while normal cells (fibroblast, endothelial) are not affected. We demonstrated that conditional sGal3 induction (tet-on system) in glioma xenografts strongly inhibits tumor growth without overt toxicity in mice. We found that Gal3-mediated tumor cell killing was neutralized with lactose, a Gal3-CRD binding ligand, and Gal3-mediated apoptosis was inhibited by treatment with a caspase 9 inhibitor (LEHD) but not by a caspase 8 inhibitor (IETD). Gal3 interacts with several glycosylated cell surface proteins. We identified that Gal3-induced tumor specific apoptosis is mediated through Gal3-beta1 integrin binding through GST-Gal3 pulldown assay, cell membrane-specific Gal3-beta1 integrin co-immunoprecipitation, and beta1 integrin siRNA neutralization. Further, the treatment of N-glycosylation inhibitor (tunicamycin) interfered with Gal3-beta1 integrin interaction whereas, O-glycosylation inhibitor (benzyl-O-N-acetyl-D-galactosamine) increased N-glycosylation of beta1 integrin as well as consequent Gal3-beta1 integrin interaction and Gal3-mediated apoptosis. In summary, our data demonstrate that extracellular Gal3 interacts with tumor cells through highly-glycosylated cell surface beta1 integrin through its CRD binding and consequently induces apoptosis. These findings are important for our understanding of tumor-specific killing of Gal3 and suggest that Gal3 can be exploited as a therapeutic agent for cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1264.
PATHOLOGIC RELATIONSHIP OF ULCER AND CARCINOMA OF THE ALIMENTARY CANAL
Authors: LOUIS BLANCHARD WILSON
Journal: JAMA (1910)

<h3>INTRODUCTORY</h3> Any line of investigation which promises assistance in combating the spread of cancer is worth while. For, discounting to the utmost government census figures everywhere, there yet remains the facts, first, that cancer is increasing materially in relation to the total number of deaths from all causes, and, second, that it is increasing materially in relation to the total number of living. Speaking broadly, it is probably increasing more rapidly than any other of our diseases. And this increase is greatest in the most prosperous nations and in the most prosperous classes within such nations. Further, it attacks individuals at their highest productive period. It attacks particularly the primary organs of perpetuation of the individual, i. e., the reproductive apparatus. In the male approximately two-thirds and in the female one-fourth of all cancers develop in the alimentary canal, while one-half of all cancers of the female are in the
NON-SPECIFIC RESISTANCE TO EXPERIMENTAL CHOLERA IN EMBRYONATED EGGS
Authors: Richard A. Finkelstein, John P. Ransom
Journal: The Journal of Experimental Medicine (1960)

It has been confirmed that 11- and 13-day-old chick embryos are susceptible to lethal infection with minute inocula of V. cholerae, while 15-day-old embryos are relatively resistant. Twenty strains of E. coli were found to vary in their capacity to kill chick embryos, without relationship to their human enteropathogenicity. Prior infection of 13-day-old embryonated eggs with E. coli strains selected for low embryo virulence had a marked protective effect against superinfection with V. cholerae. This effect was duplicated by pretreatment of embryos with killed E. coli cells or endotoxin preparations but not with a suspension of killed cells of a Gram-positive species. Preparatory E. coli infection induces a phase of vibriostasis in the 13-day-old egg which may be sufficient to tide the embryo over into the phase of relative insusceptibility associated with age. Younger embryos exhibit only a lag in death under similar conditions. The chick embryo is presented as a potentially valuable tool for the study of combined infections and of the mechanisms of natural resistance.
P3-256: The prognostic value of the Standardized Uptake Value (SUV) of FDG-PET in patients with stage I and II non-small cell lung cancer (NSCLC) treated by radical surgery
Authors: Maria J. Rops, Klaartje W. Maas, Franz M. Schramel, Fred J. Verzijlbergen
Journal: Journal of Thoracic Oncology (2007)
Tamoxifen reduces risk of breast cancer in high risk patients
Authors: D. Singh
Journal: BMJ (2003)

Prophylactic use of tamoxifen over five years reduces the incidence of breast cancer by 38% in healthy women with a high risk of developing the disease, a study published in the Lancet says (2003;361:296-300).

The authors, from Cancer Research UK, conducted an extensive review of 14 trials involving over 40 000 women. Four of the trials tested the role of tamoxifen as a preventive treatment in 28 000 women, and another trial, involving 7700 women, tested the role of raloxifene instead. Both drugs were compared with a placebo. In nine trials 15 000 women who had had a tumour removed from one breast were treated with tamoxifen to prevent the cancer returning.

The study found that in healthy women with a high chance of developing the disease tamoxifen reduced the incidence …
Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1−/y mice
Authors: Yu Zhang, Audrey Bonnan, Guillaume Bony, Isabelle Ferezou, Susanna Pietropaolo, Melanie Ginger, Nathalie Sans, Jean Rossier, Ben Oostra, Gwen LeMasson, Andreas Frick
Journal: Nature Neuroscience (2014)
Integrative genomics in cardiovascular medicine
Authors: J. S. Ware, E. Petretto, S. A. Cook
Journal: Cardiovascular Research (2012)

Integrative genomics studies have greatly advanced our understanding of cardiovascular pathophysiology over the last decade. Here, we highlight the strengths and challenges of this cutting-edge approach and provide examples where novel insights have arisen through the integration of multi-level genomic information and cardiac physiology. Going forward, the integration of comprehensive next-generation sequencing data sets with quantitative phenotypes at the molecular, cellular, and whole-heart level using advanced modelling approaches provides an unprecedented opportunity for cardiovascular science.
The peroxisome proliferator-activated receptor-α agonist, BAY PP1, attenuates renal fibrosis in rats
Authors: Peter Boor, Peter Celec, Ina V. Martin, Luigi Villa, Július Hodosy, Kristína Klenovicsová, Ciro Esposito, Stefan Schäfer, Barbara Albrecht-Küpper, Tammo Ostendorf, August Heidland, Katarína Šebeková
Journal: Kidney International (2011)
2 - Methyl - 1: 4 - Naphthoquinone
Authors: A. L. Bacharach
Journal: BMJ (1940)

Two types of catfish alloantigen-dependent cytotoxic T cells were cloned from PBL from a fish immunized in vivo and stimulated in vitro with the allogeneic B cell line 3B11. Because these are the first clonal cytotoxic T cell lines derived from an ectothermic vertebrate, studies were undertaken to characterize their recognition and cytotoxic mechanisms. The first type of CTL (group I) shows strict alloantigen specificity, i.e., they specifically kill and proliferate only in response to 3B11 cells. The second type (group II) shows broad allogeneic specificity, i.e., they kill and proliferate in response to several different allogeneic cells in addition to 3B11. “Cold” target-inhibition studies suggest that group II CTL recognize their targets via a single receptor, because the killing of one allotarget can be inhibited by a different allotarget. Both types of catfish CTL form conjugates with and kill targets by apoptosis. Killing by Ag-specific cytotoxic T cells (group I) was completely inhibited by treatment with EGTA or concanamycin A, and this killing is sensitive to PMSF inhibition, suggesting that killing was mediated exclusively by the secretory perforin/granzyme mechanism. In contrast, killing by the broadly specific T cytotoxic cells (group II) was only partially inhibited by either EGTA or concanamycin A, suggesting that these cells use a cytotoxic mechanism in addition to that involving perforin/granzyme. Consistent with the presumed use of a secretory pathway, both groups of CTL possess putative lytic granules. These results suggest that catfish CTL show heterogeneity with respect to target recognition and cytotoxic mechanisms.
Building-Related Illnesses
Authors: D Menzies, J Bourbeau
Journal: New England Journal of Medicine (1997)

Over the past 30 years, a new man-made ecosystem has developed — the controlled indoor environment within the sealed exterior shells of modern office buildings. This new environment has considerable potential to affect public health because more than half the adult work force in North America and Western Europe works in offices or “office-like” nonindustrial environments.1 The indoor environment of modern office buildings may be affected by the occupants, their work activities, equipment, plants, furnishings, building materials, ventilation systems, and outdoor air pollution. In the vast majority of buildings, this complex environment is controlled by one or two technicians who . . .
Temporal Trends in Cardiogenic Shock Complicating Acute Myocardial Infarction
Authors: Robert J. Goldberg, Navid A. Samad, Jorge Yarzebski, Jerry Gurwitz, Carol Bigelow, Joel M. Gore
Journal: New England Journal of Medicine (1999)

Limited information is available on trends in the incidence of and mortality due to cardiogenic shock complicating acute myocardial infarction. We studied the incidence of cardiogenic shock complicating acute myocardial infarction and in-hospital death rates among patients with this condition in a single community from 1975 through 1997.
Opportunity to discuss voluntary family planning was missed in spotlight on climate change
Authors: J. Guillebaud
Journal: BMJ (2012)

Voluntary family planning as a relevant intervention was mentioned only briefly in two of the nine articles of the spotlight on climate change and was not mentioned at all in the article entitled “What needs to be done.” 1 2 3 Otherwise, population growth featured not as something for humankind to address—wisely and compassionately—but as a given to which we must try hopelessly to adapt.

Why hopelessly? Because the required scale of …
King Tutankhamun’s Family and Demise—Reply
Authors: Yehia Z. Gad
Journal: JAMA (2010)

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IMPACT OF CLOPIDOGREL PRETREATMENT ON ISCHEMIC COMPLICATIONS OF PCI AMONG BIVALIRUDIN-TREATED PATIENTS: RESULTS FROM THE EVENT REGISTRY
Authors: Amit P. Amin, Kevin Kennedy, Michael Pencina, Peter Berger, Robert N. Piana, John Lopez, Neil Kleiman, David J. Cohen
Journal: Journal of the American College of Cardiology (2010)