tbuckley/cabot-search huggingface dataset:
Abstract 3837: Effect of matrix and intercellular interactions on chemotherapeutic efficacy in a high-throughput format.
Authors: Christine L. O'Day, Yoko Ejiri, Masaya Hosoda
Journal: Cancer Research (2013)

Abstract Many researchers believe that clinical results often do not coincide with two-dimensional in vitro assays, prompting the need for better correlative cellular models. 3D culture has gained much interest in recent years for the effects of matrix and inter-cellular contacts on tumor growth and progression. We have devised a high throughput assay to look at the effects of matrix and intracellular interactions using a standard 384 2D plate, matrigel in 384 well format and 3D Elplasia micro-space plates with a 200 micron grid. We standardized the media between all three platforms but decreased the cell number 3-4 fold in 2D plates to keep growth within the linear range for a 6 day assay. Media was changed once after 3 days. In all cell lines tested, there were at least one doubling of cell number in 6 days and the rate of growth was fairly consistent between 3D and 2D techniques, with 2D growth slightly faster. We examined differences in potency and efficacy of 6 different agents in 10 cell lines comparing 2D and 3D techniques. These agents are directed at PI3K, DR4/5, MEK, EGFR, and BCL2. Effects due to matrix interactions vs. suspension were noted along with potency and efficacy changes of several compounds when compared to 2D but not in all cells lines. Often EC-50 values for various agents were identical between platforms. In a few cell lines, the potency of a PI3K/mTorr inhibitor was increased three fold but the overall efficacy (defined by area under the curve) was decreased in 2D vs. 3D. DR4/5 agonists also had a mixed profile with some cell lines. TRAIL was dramatically more potent in 2D for some lines and conversely, more potent for others in 3D. Ranges of over 10 fold in EC-50 for Trail were observed between 2D and 3D in the same cell line. This interesting variation between 2D and 3D endpoints prompts the need to correlate 3D potency with clinical data and begs insight into the reasons behind the differences in receptor mediated signaling in 3D. If 3D is more correlative, which many studies suggest, there will be a clear benefit to screening multiple cell lines for efficacy and correlating them with gene expression data in 3D culture for biomarker identification. Citation Format: Christine L. O'Day, Yoko Ejiri, Masaya Hosoda. Effect of matrix and intercellular interactions on chemotherapeutic efficacy in a high-throughput format. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3837. doi:10.1158/1538-7445.AM2013-3837
Carthage Must Be Destroyed
Authors: J. J. Robbins
Journal: JAMA (1967)

<h3>To the Editor:—</h3> In their article, "Status Asthmaticus In Children" (<b>201</b>:75, 1967), Richards et al state that 1% to 2% of children with asthma eventually die of the disease. On the basis of their estimate of incidence of 4% to 10% of the general population said to have suffered at sometime from asthma, this would mean 8,000 deaths from asthma a year, or more. In contrast Snapper and Kohn (<i>Bedside Medicine</i>, ed 2, New York: Grune &amp; Stratton, Inc., 1967, p 296) state: Between 1886 and 1906, only 7 autopsy cases of status asthmaticus were published. Evidently hardly ever did anybody die of an asthmatic attack; the consultants with the most extensive practices wrote that they knew of
Francis Cameron Edington
Authors: Hugh C Barr
Journal: BMJ (2004)

Former general practitioner Penrith, Cumbria (b 1904; q Edinburgh 1939), d 26 February 2004.​2004.




Figure 1




Before studying medicine he farmed in northern Ontario, Canada. After qualifying and a short period working in the Edinburgh Royal Infirmary, he joined the Royal Navy. He served, during the second world war, as a medical officer on various ships, destroyers in the north Atlantic convoys, and minelayers in the Arctic Circle, before joining the aircraft carrier Shah in the Far East as surgeon-lieutenant commander. He was mentioned in dispatches for saving the life of a drowning man in Liverpool docks. The Shah was involved in one of the last sea battles against the Japanese. After the war he joined his father and brother in general practice, where he stayed until his retirement in 1969. Predeceased by his wife, Anella, he leaves two sons and three grandchildren.
Chloramphenicol for Long-Term Therapy of Cystic Fibrosis
Authors: Anne V. C. Lloyd
Journal: JAMA (1963)

In order to determine the effects of continued administration of chloramphenicol, the authors selected 50 children with cystic fibrosis whose periods of treatment with chloramphenicol exceeded 3 years. The authors also reviewed the postmortem findings in a group of 23 patients who had been treated for periods up to 6 years. In both groups evidence of toxicity was sought, especially with respect to blood and bone marrow. The bone marrow of 12 patients in the first group showed changes to be expected in infectious processes, but in neither group was there evidence that the hematopoietic functions of the bone marrow had been depressed by chloramphenicol in the dosages used.
Erratum: Not a Way to do Esophageal Bougienage
Authors: R. P. Bhutiawi, A. J. Warrington
Journal: Endoscopy (1991)

Correction to: Not a Way to do Esophageal BougienageEndoscopy 1990; 22(05): 239-239DOI: 10.1055/s-2007-1010735
Defining Challenges and Proposing Solutions for Control of the Virus Vector Aedes aegypti
Authors: Amy C Morrison, Emily Zielinski-Gutierrez, Thomas W Scott, Ronald Rosenberg
Journal: PLoS Medicine (2008)

T he mosquito Aedes aegypti is the primary vector of three important viral diseases-dengue, yellow fever, and chikungunya-and is capable of transmitting a number of others.Ae. aegypti, which bites during daylight, is uniquely domestic among mosquito vectors: it mates, feeds, rests, and lays eggs in and around human habitation.Control of this mosquito should lead to control of disease, and there are well-documented historical examples of both yellow fever and dengue being eliminated or significantly reduced through Ae. aegypti control [1].Construction of the Panama Canal was possible only after US Army Surgeon General William Gorgas stopped yellow fever transmission among workers by eliminating Ae. aegypti breeding sites.Fred Soper, of the Rockefeller Foundation, led the highly successful Ae.aegypti eradication program during the 1950s and 1960s that extinguished yellow fever and dengue transmission from most of Central and South America.More recently, Singapore and Cuba greatly reduced risk of dengue transmission by means of anti-Ae.aegypti legislation and actions.Use of the predatory crustacean Mesocyclops is preventing dengue transmission in parts of Vietnam [2].Unfortunately, these successes are exceptions that were often too shortlived.Dengue has reoccupied Latin America and increases yearly; most of Southeast Asia remains highly endemic.Despite the availability of a vaccine, yellow fever outbreaks occur with dismaying frequency in Africa and Latin America.Chikungunya caused epidemics during 2005-2006 in the Indian Ocean region that were the largest yet recorded.In some regions, such as Sudan, all three viruses coexist.The reasons for failure are numerous.Spreading urbanization increases the habitat for expanding Ae. aegypti populations, rapid global migration increases the potential for vector and virus dissemination, poverty hobbles the efforts of individuals and communities to carry out effective protective measures, and even when resources for control exist, they are too often ineffectively applied [3].An international panel (see Acknowledgments) met at Fort Collins, Colorado, United States, in May 2006 to critically examine why Ae. aegypti control has so seldom been successful in eliminating disease and to recommend measures to increase the opportunities for success.Consideration of control methods was limited to technologies now available or that could be soon developed; therefore, methods depending on genetical manipulation, such as genomic transformations and sterile male releases, were not discussed.There was unanimous agreement that elimination or significant reduction of Ae. aegypti populations is an effective and proven method for disease prevention.After reviewing examples of successful and failed programs, two issues especially worthy of attention were identified: (1) program design and management-specifically, sustainability, goal-setting, and surveillance/assessment-and (2)
Evaluation of Four-Year Coronary Artery Response After Sirolimus-Eluting Stent Implantation Using Serial Quantitative Intravascular Ultrasound and Computer-Assisted Grayscale Value Analysis for Plaque Composition in Event-Free Patients
Authors: Jiro Aoki, Alexandre C. Abizaid, Patrick W. Serruys, Andrew T.L. Ong, Eric Boersma, J. Eduardo Sousa, Nico Bruining
Journal: Journal of the American College of Cardiology (2005)
Glucocorticoids decrease tissue mast cell number by reducing the production of the c-kit ligand, stem cell factor, by resident cells: in vitro and in vivo evidence in murine systems.
Authors: S Finotto, Y A Mekori, D D Metcalfe
Journal: Journal of Clinical Investigation (1997)

The local delivery of glucocorticoids to tissues significantly decreases mast cell number. This pharmacologic effect of glucocorticoids is believed to be one of the mechanisms by which glucocorticoids regulate allergic inflammation. To determine the mechanism by which glucocorticoids are able to exert this effect, we first applied the glucocorticoid fluocinonide to mouse dermis and observed that the decrease in mast cell number was associated with an increase in mast cell apoptosis. This did not appear to be due to a direct effect of the glucocorticoid on mast cells, as the addition of 0.01-1.0 microM of the glucocorticoid dexamethasone into stem cell factor (SCF)-dependent mast cell cultures did not enhance mast cell death. However, addition of dexamethasone to cultured fibroblasts did result in a downregulation of SCF mRNA and a significant decrease in SCF protein production. Similarly, immunohistochemistry performed on fluocinonide-treated mouse dermis revealed a decrease in immunoreactive SCF. Administration of SCF at sites of fluocinonide administration to the dermis abolished the mast cell-depleting effect of this glucocorticoid. Thus, glucocorticoids decrease tissue mast cell number by downregulating tissue SCF production required for the survival of local mast cells. This observation may be applicable to the design of improved strategies to treat mast cell-mediated disorders.
Case 28-1986
Authors: James R. Kasser, Andrew E. Rosenberg
Journal: New England Journal of Medicine (1986)

Presentation of CaseAn eight-year-old girl was admitted to the hospital because of multiple osteolytic lesions.She was well until approximately six months earlier, when varicella occurred; after several weeks at home she returned to school. During the next week or two the child complained of intermittent fleeting pains in the left ankle, but her parents found no objective abnormality. Five months before admission the ankle pain increased, and mild local swelling was observed about the ankle. A day or two later swelling was noticed over the medial aspect of the right clavicle. The child recalled minor injury to the . . .
Abstract 1273: Adaptive immunity in a zebrafish model of melanoma.
Authors: Corrie A. Painter, Craig Ceol
Journal: Cancer Research (2013)

Abstract The recent success of the anti-CLTA-4 antibody, ipilimumab, for late stage metastatic melanoma, provides proof of principle that stimulating the immune system can have profound effects on patient outcome. However, a detailed understanding of the role of immune-modulating cells within the tumor microenvironment has been confounded by the lack of a suitable model system that would allow for direct visualization of cells within the intact tumor microenvironment. Previous work has demonstrated that the zebrafish, Danio Rerio, can be genetically manipulated to produce melanomas that recapitulate BRAFV600E;P53-/- human tumors. Due to its translucency, ease of genetic manipulation and high fecundity, the zebrafish is an attractive model system that allows for in vivo characterization of cells within intact tissue. Using this model system, we have begun investigating the adaptive immune response to melanoma in zebrafish. We have focused our initial investigations on determining whether transcript expression of key adaptive immune-modulatory proteins are present in the zebrafish and to what extent they are expressed intratumorally . Our studies have found that orthologs of CLTA-4, FOXP3, and CD8 are all expressed in wild-type zebrafish, but not in rag-/- zebrafish. Furthermore, transcript levels of CTLA-4 were greatest in the melanoma tumor relative to other regions of the zebrafish, which is consistent with the constitutive expression of CTLA-4 in human melanomas. Additionally, we have cloned the promoters for zebrafish FOXP3 and CD8 and are developing fluorescent reporter lines that will enable us to visualize and ablate subpopulations of T cells within the tumor. These lines, along with previously described reporter lines for MHC II and lck, will enable us to determine the role of adaptive immune cells during melanoma onset and progression in the zebrafish. Our research supports the notion that there is conservation between the human and zebrafish adaptive immune systems, and that similar immune evasion mechanisms may be contributing to melanoma growth in zebrafish. These data position the zebrafsh as a powerful model system for immunological investigations that focus on the adaptive immune response to melanoma. Citation Format: Corrie A. Painter, Craig Ceol. Adaptive immunity in a zebrafish model of melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1273. doi:10.1158/1538-7445.AM2013-1273
Recent Advances in Blood Coagulation
Authors: K. M. Brinkhous
Journal: JAMA (1977)

This volume contains 14 chapters, each with different authorship, on various aspects of the clotting mechanisms and its abnormalities. Of the 20 authors, half are from Great Britain and Ireland. The first two chapters, Biochemistry of Blood Coagulation (Baugh and Hougie) and Activation and Interaction of Some Defense Systems (Stormorken), give a good overview of the field, with most recent references being to 1975 articles. The reader gets a good description of the discovery of the calcium-binding function of the novel amino acids γ-carboxyglutamic acid, in the vitamin K— dependent procoagulants, prothrombin, and factors VII, IX, and X; the newer procoagulants, concerned with the early phase of clotting, prekallikrein, and high-molecular-weight kininogen, are discussed. The evidence demonstrates that the products of the early contact stages of the so-called intrinsic system of clotting, including factor XII and the kallikrein-kinin system, trigger not only the interaction of the antihemophilia factors VIII and
Bone Repair: Osteotropic Therapy via Targeted Layer‐by‐Layer Nanoparticles (Adv. Healthcare Mater. 6/2014)
Authors: Stephen W. Morton, Nisarg J. Shah, Mohiuddin A. Quadir, Zhou J. Deng, Zhiyong Poon, Paula T. Hammond
Journal: Advanced Healthcare Materials (2014)

Nanomedicine that can target bone tissue for disease treatment is designed by P. Hammond and team on page 867 by modifying the surface of therapeutic-containing particles with nanolayers of a polymer decorated with moieties that specifically bind boney regions. In this way, drug therapies can be directed to diseased bone tissue for improved treatment outcomes. LbL on nanoparticles is a versatile platform for tuning tissue specificity and therapeutic efficacy, in a controlled manner, one layer at a time.
Hospitalizations for Firearm-Related Injuries
Authors: Mary J. Vassar
Journal: JAMA (1996)

To determine the incidence, nature, demographics, severity, and hospital charges associated with inpatient treatment of firearm-related injuries.A retrospective, 1-year, population-based study of firearm-related hospitalizations based on the 1991 California Hospital Discharge Abstract Data Tapes.California acute care hospitals that reported firearm-related discharges.A total of 9562 patients discharged with firearm-related injuries.Per capita hospital discharge rates, according to age, race, and sex.A total of 9562 firearm-injured persons were discharged from California hospitals in 1991, representing a rate of 32 discharges per 100 000 population. Males aged 15 to 24 years accounted for 72% of the hospitalizations. For all causes of firearm-related injury, the highest age- and race-specific discharge rate was 439 per 100,000 for black persons aged 15 to 24 years. The highest county discharge rate was 55 per 100,000 for Los Angeles County. Statewide, there were 1.8 hospital discharges per firearm-related fatality (both in the hospital and in the community). Assaults accounted for 74% of cases. Among black males aged 15 to 24 years, assaults accounted for 598 discharges per 100 000 population. Hospital charges for 9193 patients exceeded $164 million; mean and median charges per patient discharged were $17,888 and $8535, respectively. Publicly financed health insurance programs sponsored 56% of patients; 25% had private insurance, and 19% were uninsured. Fifty-three percent of the discharges occurred at 13 of the 371 hospitals that discharged patients with firearm-related injuries.Firearm-related violence is a major cause of hospitalization of young urban black males and represents a significant cost to publicly financed health care. The impact on individual hospitals is highly disproportionate. While hospital discharge data can be used for population-based surveillance of firearm-related trauma, there is need for improvement in local, state, and national surveillance of these injuries.
Proximal Type Epithelioid Sarcoma of the Scrotum: A Source of Diagnostic Confusion That Needs Immediate Attention
Authors: Fikret Fatih Onol, Yılören Tanıdır, Esin Kotiloğlu, Mehmet Bayramiçli, Serdar Turhal, Levent N. Türkeri
Journal: European Urology (2005)
Concomitant Asthma Medication Use in Patients Using Omalizumab: Results from Three Large Insurance Claims Databases
Authors: M. Lafeuille, M.S. Duh, J. Zhang, D. Wertz, T. Gu, J. Tang, A. Swensen, E.L. Stanley, P. Lefebvre
Journal: Journal of Allergy and Clinical Immunology (2011)
Leukocytosis and Artifactual Hypoglycemia
Authors: Thomas J. Goodenow
Journal: JAMA (1977)

Two patients are described with asymptomatic low blood glucose and excessive in vitro consumption of glucose by leukocytes before separation of the serum for assay. This may be a more common problem than is appreciated and need not be associated with leukemia or extreme leukocytosis. The circumstances that allow this avoidable type of artifactual hypoglycemia may also produce factitious euglycemia during evaluation of suspected diabetes mellitus.
Address in Therapeutics
Authors: W. Roberts
Journal: BMJ (1885)

GENTLEMENT,-My first duty is to expreSs my acknowledgments to the Council of the Association, aid 'to 'the South Wales and Monmouthshire Branch, for the honour they 'y, dpne me in inviting me to deliver the Address in Therapeuitics.Thip i; t believe, the first occasion in the history of the Association whi.zh, 'from the wide domain of medicine, that portion which deals with;the treatment of the sick has been specially selected as the tL.eh of, an address at the annual meeting.The subject of therapeutics 'is jq larg and complex, that to deal with it comprehensively within the, com, pms of an hour's address would be beyond my powers.Such at, -tempt, even in much abler hands than mine, could scardel.' issue btherwise than in the enunciation of a series of barten generlitieo 'which would edify no one.I therefore felt, as soon as t;,canie to P9nsider the matter, that the most prudent course for me, and the one ..Most likely to prove interesting to you, was to confine.'lysef to a very limited area in the field of therapeutics, and to etdAvour, within that area, to say something which might prove of use in the daily practice of your profession.Perhaps, of all the many duties which fall to the province, of the medical practitioner, there is none so common as the duty of reglat- ing the diet of his patients.Whatever the disease may be from which the patient is suffering, and whatever special means may be iadicated for his relief, the regulation of the diet is sure, sooner or later, to crop up as an integral part of the management of the case.Dietetics, therefore, cover more ground than any other branch of the healing art-they are also, perhaps, the most ancient branch.Hippocrates traces back the very origin of medicine to dietetics." For,' he says, "the art of medicine would not have been invented at Art nor would it have been made a subject of investigationi, if, when men are indisposed, the same food, and other articles of regimen which they eat and drink when in good health, were proper for ithem, and if no others were preferable to these." Notwithstanding this universal aplicability, and this high antiquity, it must, I think, be allowed that dietetics, except in a few special cases, are somewhat neglected in these days.The often contradictory advice which is tendered to invalids in regard to their diet by the several medical men whom.they may consult, betrays the want of a guiding principle, and of a general consensus of opinion in the medical profession on the subject of feeding the sick.This is, perhaps, not to be wondered at when it is considered how little systematic study is devoted to dietetics, and how fragmentary is the instruction on this subject which is given to the student of medicine.So far as I know, there is no systematic teaching of dietetics, even on the most limited scale, afforded to the' 'ciency natitmal piogrea and ascendancy deplend.A good mnany in- 8M
Take a deep breath: pulmonary research inspires
Authors: Paul W. Noble
Journal: Journal of Clinical Investigation (2012)

The lung is a complex organ with multiple functions; in addition to facilitating gas exchange, it also serves as the first line of defense against inhaled environmental pathogens and toxins. Given these critical roles, disruption of normal cell function or cell-cell interactions can have devastating health consequences. The articles of this Review Series highlight recent progress in understanding the pathophysiology of several pulmonary diseases and suggest how these insights are leading to the development of new therapeutic strategies.