tbuckley/cabot-search huggingface dataset:
Abstract LB-349: Tumor associated macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase.
Authors: Yoav Binenboum, Noam Weissman, Yakov Kerlin, Ayelet Shabtai, Moran Amit, Ziv Gil
Journal: Cancer Research (2013)

Abstract Resistance to pharmacologic agents used in chemotherapy is a common phenomenon in most human carcinomas. Pancreatic ductal adenocarcinoma (PDA) is such a tumor, which is resistant to almost all drugs, including gemcitabine, a new nucleoside analog used as first-line treatment. For this reason the poor survival of patients with PDA have not change much during the last 4 decades. Recent data indicated that tumor-associated macrophages (TAMs) which are abundant in the microenvironment of several tumors, including PDA, secrete pro-tumorigenic factors which contribute to cancer progression and dissemination. In this study, we show for the first time that TAMs can also induce chemoresistance of PDA by reducing gemcitabine-induced apoptosis. Macrophages co-cultures with cancer cells or TAMs conditioned medium significantly reduced the levels of cleaved caspase-3 and caspase-3 during gemcitabine treatment. An in vivo PDA model of CCR2-deficient mice, which have reduced macrophage recruitment and activation, demonstrated improved response to gemcitabine compared to wild-types. Similarly, inhibition of monocytes/macrophages trafficking by a CSF1-receptors antagonist augmented the effect of gemcitabine in a transgenic mouse model of PDA that was resistant to gemcitabine alone. Analysis of multiple proteins involved in gemcitabine delivery and metabolism revealed that TAMs induced upregulation of cytidine deaminase (CDA), the enzyme that metabolizes the active form of the drug. Decreasing of CDA expression by PDA cells blocked the protective effect of TAMs against gemcitabine. Taken together, our results identify a paracrine effect of TAMs on PDA cells, which mediates acquire resistance of cancer cells to chemotherapy. Modulation of macrophage trafficking or inhibition of CDA may offer a new strategy for augmenting the response of PDA to chemotherapy. Citation Format: Yoav Binenboum, Noam Weissman, Yakov Kerlin, Ayelet Shabtai, Moran Amit, Ziv Gil. Tumor associated macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. [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 LB-349. doi:10.1158/1538-7445.AM2013-LB-349 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
937 SAFETY, TOLERABILITY, AND PHARMACOKINETICS AFTER SINGLE AND MULTIPLE DOSES OF MK-3281 IN HEALTHY SUBJECTS
Authors: D. Brainard, D.H. Wright, K. Sneddon, C. Cummings, P. Sun, J. Valentine, M. Anderson, S. Warrington, B. Sanderson, J. Chodakewitz, J. Wagner
Journal: Journal of Hepatology (2009)
Screening Tests in Ambulatory Practice
Authors: N. A. Cohen
Journal: JAMA (1971)

<h3>To the Editor.—</h3> In regard to "Physicians' Use and Opinions of Screening Tests in Ambulatory Practice," (<b>214</b>:2173. 1970), Bates and Mulinare's communication probably was meant to be and certainly is thought provoking; however, I must disagree with portions of it. Continuing from a quotation of Feinstein's, the authors refer to the physicians' need to think in terms of specificity, sensitivity, reliability, and yield. In view of that statement and in view of the poor specificity, sensitivity, and reliability of the most commonly used multiple-channel screening chemistry machine, the next sentence of the communication, "We cannot yet define the optimal place of screening examinations in the health care system" should be italicized, as possibly should be the sentence following it. However, my most serious disagreement with the authors' concept is what they state in their last sentence, ie, their conclusion that physicians fear losing professional control over their practices. It
A Prospective Study of Holiday Weight Gain
Authors: Jack A. Yanovski, Susan Z. Yanovski, Kara N. Sovik, Tuc T. Nguyen, Patrick M. O'Neil, Nancy G. Sebring
Journal: New England Journal of Medicine (2000)

It is commonly asserted that the average American gains 5 lb (2.3 kg) or more over the holiday period between Thanksgiving and New Year's Day, yet few data support this statement.
Visualization of CD4/CD8 T Cell Commitment
Authors: Susan Chan, Margarida Correia-Neves, Andrée Dierich, Christophe Benoist, Diane Mathis
Journal: The Journal of Experimental Medicine (1998)

A system to innocuously visualize T cell lineage commitment is described. Using a “knock-in” approach, we have generated mice expressing a β-galactosidase reporter in place of CD4; expression of β-galactosidase in these animals appears to be an accurate and early indicator of CD4 gene transcription. We have exploited this knock-in line to trace CD4/CD8 lineage commitment in the thymus, avoiding important pitfalls of past experimental approaches. Our results argue in favor of a selective model of thymocyte commitment, demonstrating a fundamentally symmetrical process: engagement of either class of major histocompatibility complex (MHC) molecule by a differentiating CD4+CD8+ cell can give rise to T cell antigen receptor (TCR)hi thymocytes of either lineage. Key findings include (a) direct demonstration of a substantial number of CD4-committed, receptor/coreceptor-mismatched cells in MHC class II– deficient mice, a critical prediction of the selective model; (b) highly efficient rescue of such “mismatched” intermediates by forced expression of CD8 in a TCR transgenic line, and an explanation of why previous experiments of this nature were less successful—a major past criticism of the selective model; (c) direct demonstration of an analogous, though smaller, population of CD8-committed mismatched intermediates in class I–deficient animals. Finally, we found no evidence of a CD4 default pathway.
A SUPERFICIAL DRAIN
Authors: Herbert T. Wikle
Journal: JAMA (1922)

Realizing the importance of small incisions with free drainage, particularly in infections of the face, I have been using, in preference to rubber tissue or rubber band forms of drains, a small drain made from horsehair. The horsehair may be kept in a small jar of alcohol; and, when a drain is needed, one of the horsehairs is removed from the jar and wrapped tightly and closely about a probe, as illustrated at<i>a</i>in the accompanying illustration. The portion of the probe about which the horsehair is wrapped is then passed through the flame of an alcohol lamp. This helps to sterilize and dry out the horsehair, and makes it set in the desired shape, that of a coil, as illustrated at<i>b</i>. The size of the drain depends, of course, on the diameter of the probe about which it is wrapped. The horsehair is then removed from the
Antibodies in human brucellosis.
Authors: J. D. Coghlan, D. M. Weir
Journal: BMJ (1967)

There have been a number of studies of the serological and immunological properties of brucella antibodies in man and animals. Vaerman et al. (1963) and Wilkinson (1966) have shown that all three major classes of immunoglobulin are involved at some time during the course of infection. The former workers showed that three purified immunoglobulins, known as IgG, IgA, and IgM, obtained from the serum of cases of brucellosis contained brucella agglutinating antibodies, and Wilkinson, using mainly cattle sera, found that when each of [hese immunoglobulins was removed by specific precipitating rabbit anti-human IgG, IgA, and IgM sera this resulted in rhe inhibition of their serological activity. Anderson et al. '1964) and Reddin et al. (1965) reported changes in serological activity during the course of the disease, and it seemed likely that analysis of a serum at different stages of the disease to determine in which fraction its serological activity lies might ?ive information of value in diagnosis, as has been indicated m a previous study (Kerr et al., 1966). The present report is an attempt to relate the serological response at various stages of acute brucellosis to the types of globulin present at these stages, and to compare these findings with those found in sera from a group of veterinary surgeons who, while no longer acutely infected, may have been suffering from the disease in its chronic form or may have had their mmune responses from a previous infection stimulated by repeated contact with the organism in the course of their work.
Pitfalls of Colony Count Of Urine Cultures
Authors: Sumner Marshall
Journal: JAMA (1968)

<h3>To the Editor:—</h3> In the collection of a urine specimen for culture, great emphasis is placed on plating out the specimen immediately, lest there be gross error in the colony count from bacterial multiplication while the urine sits on the shelf. Yet the physician rarely questions either the length of time the urine remains in the bladder (ie, the time of previous voiding) or the specific gravity of the urine. A person with a urinary tract infection may have urinary frequency both from the irritability of the inflamed bladder as well as from a high fluid intake, thereby decreasing the time of previous voiding as well as the specific gravity of the urine. Both of these would decrease the colony count. A series of patients with cystitis were subjected to sequential urine cultures in an attempt to compare the effect on colony count of incubation in the bladder with that
A fibrous stromal component in hepatocellular carcinoma reveals a cholangiocarcinoma-like gene expression trait and epithelial-mesenchymal transition
Authors: Jae Yeon Seok, Deuk Chae Na, Hyun Goo Woo, Massimo Roncalli, So Mee Kwon, Jeong Eun Yoo, Ei Yong Ahn, Gwang Il Kim, Jin-Sub Choi, Young Bae Kim, Young Nyun Park
Journal: Hepatology (2012)

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. The phenotypic overlap between HCC and CC has been shown to comprise a continuous liver cancer spectrum. As a proof of this concept, a recent study demonstrated a genomic subtype of HCC that expressed CC-like gene expression traits, such as CC-like HCC, which revealed the common genomic trait of stem-cell–like properties and aggressive clinical outcomes. Scirrhous HCC (S-HCC), a rare variant of HCC, is characterized by abundant fibrous stroma and has been known to express several liver stem/progenitor cell markers. This suggests that S-HCC may harbor common intermediate traits between HCC and CC, including stem-cell traits, which are similar to those of CC-like HCC. However, the molecular and pathological characteristics of S-HCC have not been fully evaluated. By performing gene-expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of S-HCC with those of CC and HCC. S-HCC expresses both CC-like and stem-cell–like genomic traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of S-HCC. Overexpression of transforming growth factor beta (TGF-β) signaling was also found, implying its regulatory role in the pathobiology of S-HCC. Conclusion: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene-expression traits in HCC. The expression of stem-cell–like traits and TGF-β/EMT molecules may play a pivotal role in the aggressive phenotyping of S-HCC.
Renal Failure with Extreme Hyperpotassemia
Authors: Richard B. Goldbloom
Journal: New England Journal of Medicine (1954)

THE basic purpose of therapy in acute renal failure is to reduce the accumulation of toxic substances until there is sufficient return of renal function to maintain homeostasis. To this end, a variety of technics for artificial dialysis have been developed. The simplest of these involves irrigation of the gastrointestinal tract or peritoneal cavity with a dialyzing solution. More recently, the favored method has been the use of some form of "artificial kidney," in which the blood is circulated extracorporeally through an artificial semipermeable membrane in the presence of a suitable dialyzing solution. These methods have several disadvantages. They require . . .
AN INSTRUMENT FOR TESTING THE LIGHT-REFLEX OF THE PUPIL.
Authors: C. A. VEASEY
Journal: JAMA (1907)

Those of us who have to make many examinations of neurologic patients have been confronted frequently with the great difficulty of obtaining satisfactory tests of the pupil light reflex. This is especially true when, for purposes of cerebral localization, it is desired to ascertain whether or not Wernicke's symptom (the hemianopic pupil inaction sign) is present. For ordinary purposes alternately covering and uncovering the eye with the hand permitting its exposure to the light of a candle, lamp or window is all that is necessary, but in those cases of very sluggish or very contracted pupils, such as are frequently observed in cerebral or spinal disease, it is essential to concentrate the light in order to ascertain whether the reflex is present or absent. In order to make the test for Wernicke's hemianopic pupillary inaction symptom light can not be employed in the ordinary manner, as it is impossible to
Global optimization of somatic variant identification in cancer genomes with a global community challenge
Authors: Paul C Boutros, Adam D Ewing, Kyle Ellrott, Thea C Norman, Kristen K Dang, Yin Hu, Michael R Kellen, Christine Suver, J Christopher Bare, Lincoln D Stein, Paul T Spellman, Gustavo Stolovitzky, Stephen H Friend, Adam A Margolin, Joshua M Stuart
Journal: Nature Genetics (2014)

Global optimization of somatic variant identification in cancer genomes with a global community challenge
Arteriovenous Fistula Following Blunt Trauma
Authors: P. H. Frandsen
Journal: BMJ (1958)

BDIBNSRNAL 895 outnumbered those of group 1II by more than 3 to 1I the proportion of type 80 strains was 72%.Type 80 strains were associated with a variety of infective conditions, some of which may have been acquired in hos- pital.The proportion of type 80 strains among staphylo- cocci recovered from different sources ranged from 32% (skin lesions) to 48% (wounds, burns, and fractures).There was no indication that type 80 infections occurred as part of a definite " outbreak "; between 20% and 60% of each of five batches of strains received over 17 months were of this type.The high incidence of penicillin resistance among type 80 strains accords with experience elsewhere.These staphylo- cocci, possessing a distinctive lytic pattern and a marked insensitivity to penicillin, seem to form a group of con- siderable pathogenic potentiality.From the lysogenic stand- point, the 98 strains classed as type 80 were not homogeneous, nine strains liberating a phage to which all the remaining type 80 strains were sensitive.It would appear that type 80 strains, like type 52A strains, possess properties which favour their growth and spread in man; further data relating to their prevalence among the patients and staff of hospitals in tropical Africa would be valuable.Summary Strains of Staph.aureus type 80 formed 40% of 248 cultures of coagulase-positive staphylococci re- covered from patients suffering from various infective conditions in Uganda.Type 80 strains were by far the commonest phage type in this series, and nearly all (97%) were penicillin-resistant. Strains of this type appear to be responsible for serious infections; their prevalence among hospital workers deserves study.We are indebted to Dr.
Laparoscopic Partial Nephrectomy with “On-Demand” Clamping Reduces Warm Ischemia Time
Authors: Renaud Bollens, Alberto Rosenblatt, Baldo P. Espinoza, Alexandre De Groote, Thierry Quackels, Thierry Roumeguere, Marc Vanden Bossche, Eric Wespes, Alexandre R. Zlotta, Claude C. Schulman
Journal: European Urology (2007)
Genetic and epigenetic insights into fetal alcohol spectrum disorders
Authors: Michèle Ramsay
Journal: Genome Medicine (2010)

The magnitude of the detrimental effects following in utero alcohol exposure, including fetal alcohol syndrome and other fetal alcohol spectrum disorders (FASD), is globally underestimated. The effects include irreversible cognitive and behavioral disabilities as a result of abnormal brain development, pre- and postnatal growth retardation and facial dysmorphism. Parental alcohol exposure and its effect on offspring has been recognized for centuries, but only recently have we begun to gain molecular insight into the mechanisms involved in alcohol teratogenesis. Genetic attributes (susceptibility and protective alleles) of the mother and the fetus contribute to the risk of developing FASD and specific additional environmental conditions, including malnutrition, have an important role. The severity of FASD depends on the level of alcohol exposure, the developmental stage at which exposure occurs and the nature of the exposure (chronic or acute), and although the most vulnerable period is during the first trimester, damage can occur throughout gestation. Preconception alcohol exposure can also have a detrimental effect on the offspring. Several developmental pathways are affected in FASD, including nervous system development, growth and remodeling of tissues, as well as metabolic pathways that regulate glucocorticoid signaling and balanced levels of retinol, insulin and nitric oxide. A body of knowledge has accumulated to support the role of environmentally induced epigenetic remodeling during gametogenesis and after conception as a key mechanism for the teratogenic effects of FASD that persist into adulthood. Transgenerational effects are likely to contribute to the global burden of alcohol-related disease. FASD results in lifelong disability and preventative programs should include both maternal alcohol abstention and preconception alcohol avoidance.
Undermining access ...
Authors: David G Samuel
Journal: BMJ (2008)

I am a student who hails from a low socioeconomic area in south Wales who knows first hand the fears that students hold regarding student debt. I think that UKCAT is nothing more than a divisive sieving exercise further to increase the divide between those who can and cannot afford to study medicine—a degree already overburdened with student debt and, now, uncertainty over postgraduate prospects and job security.1

Forcing medical students to pay the fee to undertake the test so that universities can validate its accuracy is unethical and unfair. You would not expect patients to pay to take part in a clinical trial surely?

Within a few years revision courses will have been developed that will include “how to do well at UKCAT”—yet again probably increasing the divide between the affluent and less affluent, the public schools and state schools, and those in the know from most school leavers.

Gaining entrance into medical school should be based on talents, academic ability, and overall thirst to learn. Face to face discussions are the best way to tease out the personality traits that are considered fundamental for doctors, allow their personal statement claims to be validated, and for the medical school to get an overall impression of applicants’ attitude, personality and ability. With communication skills being emphasised more and more in the undergraduate curriculum surely the interview serves as a perfect way to kick start that process.
Erratum to “The Role of Glucose Transporters in the Distribution of p-aminophenyl-α-d-mannopyranoside Modified Liposomes within Mice Brain” [J. Control. Release 182 (2014) 99–110]
Authors: Dan Du, Naidan Chang, Shouli Sun, Minghui Li, Hui Yu, Meifang Liu, Xiaoying Liu, Guangtian Wang, Haichun Li, Xunpei Liu, Shilong Geng, Qun Wang, Haisheng Peng
Journal: Journal of Controlled Release (2014)
Surgery of Rheumatoid Arthritis
Authors: B. M. Ansell
Journal: Annals of the Rheumatic Diseases (1972)

Recognizing that uncritical bibliographical surveys are useless, Cobb essays an interpretative review of epidemio- logical data on rheumatic complaints and the principal individual diseases, rheumatoid arthritis, osteoarthrosis, ankylosing spondylitis, gout, Still's disease, and connective tissue disorders.Much valuable material is considered, and in a commendably brief presentation.However, it is regrettable that those leaders in the morbidity statistics, soft-tissue rheumatism and pain in the back, receive only
Human CD14dim Monocytes Patrol and Sense Nucleic Acids and Viruses via TLR7 and TLR8 Receptors
Authors: Jérôme Cros, Nicolas Cagnard, Kevin Woollard, Natacha Patey, Shen-Ying Zhang, Brigitte Senechal, Anne Puel, Subhra K. Biswas, Despina Moshous, Capucine Picard, Jean-Philippe Jais, David D'Cruz, Jean-Laurent Casanova, Céline Trouillet, Fréderic Geissmann
Journal: Immunity (2010)

Monocytes are effectors of the inflammatory response to microbes. Human CD14+ monocytes specialize in phagocytosis and production of reactive oxygen species and secrete inflammatory cytokines in response to a broad range of microbial cues. Here, we have characterized the functions of human monocytes that lack CD14 (CD14dim) and express CD16. CD14dim monocytes were genetically distinct from natural killer cells. Gene expression analyses indicated similarities with murine patrolling Gr1dim monocytes, and they patrolled the endothelium of blood vessels after adoptive transfer, in a lymphocyte function-associated antigen-1-dependent manner. CD14dim monocytes were weak phagocytes and did not produce ROS or cytokines in response to cell-surface Toll-like receptors. Instead, they selectively produced TNF-α, IL-1β, and CCL3 in response to viruses and immune complexes containing nucleic acids, via a proinflammatory TLR7-TLR 8-MyD88-MEK pathway. Thus, CD14dim cells are bona fide monocytes involved in the innate local surveillance of tissues and the pathogenesis of autoimmune diseases.
Bone marrow dysfunction in chronic heart failure patients
Authors: B. Daan Westenbrink, Adriaan A. Voors, Rudolf A. de Boer, Jan J. Schuringa, Theo Klinkenberg, Pim van der Harst, Edo Vellenga, Dirk J. van Veldhuisen, Wiek H. van Gilst
Journal: European Journal of Heart Failure (2010)
Proposals Seek to Reduce Resistance, Boost Development of New Antibiotics
Authors: Bridget M. Kuehn
Journal: JAMA (2011)

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