tbuckley/cabot-search huggingface dataset:
Abstract 493: Antitumoral efficacy of therapeutic human anti-KIR antibody (BMS-986015/IPH2102) in a preclinical xenograft tumor model.
Authors: Caroline Sola, Fabien Chanuc, Ariane Thielens, Nicolas Fuseri, Isabelle Palacios, Mathieu Blery, Pascale André, Eric Vivier, Sophie Ugolini, Robert Graziano, François Romagne, Cécile Bonnafous
Journal: Cancer Research (2013)

Abstract Natural Killer cells (NK cells) are lymphocytes able to recognize and kill tumors for which the expression of Major Histocompatibility Complex (MHC) class I molecules is altered. This “missing self” recognition is mediated in humans by the lack of engagement of MHC class I i.e. Human Leucocyte Antigens (HLA) molecules with NK cell inhibitory receptors that include Killer Immunoglobulin-like Receptors (KIR). Some tumors escape NK cell immune surveillance by increasing the expression of HLA molecules on their surface. Consequently, blocking interactions between KIR and HLA molecules constitutes an interesting therapeutic strategy. The anti-KIR2DL1/2/3-specific monoclonal antibody, BMS-986015/IPH2102, is a human IgG4 that is being developed for treating both hematologic malignancies and solid tumors. In rodents, the MHC class I inhibitory system regulating NK cell activation is based on lectin-like family Ly49 but the KIR molecules are not expressed. The objective of this study was to develop a preclinical model to assess the efficacy of the drug candidate used in clinical trials, BMS-986015/IPH2102. Mice expressing the human NK inhibitory KIR2DL3, on the surface of NK cells were generated on a RAG-1deficient background (KIRtgRAG mice). The human B cell lymphoma cell line, 721.221, transduced with HLA-Cw3 molecule, a ligand of KIR2DL3, was intra-venously engrafted in these mice. The expression of HLA-C by tumor cells was sufficient to allow them to escape control of NK cells, leading to mice death in around 30 days. IPH2102 treatment increased mice survival in a dose dependent manner when injected at the same time as the tumor challenge. This protective effect was NK cell mediated and directly correlated with the duration of KIR saturation. Interestingly, BMS-986015/IPH2102 treatment also improved survival in therapeutic conditions i.e. when the antibody was injected 5 days after the tumor, also in a NK cell dependent manner. In conclusion, this study showed efficacy of BMS-986015/IPH2102 as single agent in a HLA-Cw3-expressing tumor model and this xenogenic pre-clinical model will be an excellent tool to investigate the therapeutic benefits of combination treatments. Citation Format: Caroline Sola, Fabien Chanuc, Ariane Thielens, Nicolas Fuseri, Isabelle Palacios, Mathieu Blery, Pascale André, Eric Vivier, Sophie Ugolini, Robert Graziano, François Romagne, Cécile Bonnafous. Antitumoral efficacy of therapeutic human anti-KIR antibody (BMS-986015/IPH2102) in a preclinical xenograft tumor model. [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 493. doi:10.1158/1538-7445.AM2013-493
Computational Genetic Mapping in Mice: The Ship Has Sailed
Authors: Ming Zheng, Steve Shafer, Guochun Liao, Hong-Hsing Liu, Gary Peltz
Journal: Science Translational Medicine (2009)

Computational haplotype-based genetic mapping can be used to discover new biological mechanisms, disease-related pathways, and unexpected uses for existing drugs. Here we discuss the benefits and limitations of this methodology, its impact on translational medicine, and its future course.
Ferrokinetics: a biologic model for plasma iron exchange in man
Authors: J. D. Cook, G. Marsaglia, J. W. Eschbach, D. D. Funk, C. A. Finch
Journal: Journal of Clinical Investigation (1970)

A method is presented for calculating internal iron kinetics. An early reflux associated with extravascular exchange and a late reflux associated with erythropoiesis are described. A biologic model of iron exchange is proposed in which erythron iron turnover is divided into an effective portion (iron fixed in circulating red cells) and wastage iron of erythropoiesis (late reflux). Nonerythroid iron exchange also has a fixed portion (parenchymal uptake) and an early reflux (lymphatic circuit), both of which correlate in amount with the amount of plasma iron. Ferrokinetic measurements in normal subjects and in various pathologic states are presented to validate the model.
Intensive Care Service Contributions and Costs
Authors: J. Francis Dammann
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Optimal care of the critically ill demands a unique patient care environment, specially trained personnel, and extensive monitoring and emergency equipment. The established success of coronary unit rhythm monitoring systems is a prime example of the benefit of such an approach. As a consequence of this increased awareness, special intensive care<i>units</i>for a variety of diseases are being developed. This rapid growth has been haphazard, without a full appreciation of the far greater value of a broad-based, multidisciplined intensive care<i>service</i>. It seems appropriate to point out the essential differences between an intensive care unit for a specific class of patients and an intensive care service. In so doing, the clear-cut advantages of the latter will become manifest. An intensive care service in contrast to an intensive care unit cuts across departmental lines, yet forms a service, totally complete within itself, directed towards the care of
Fascia lata valves: a clinicopathological study.
Authors: E G Olsen, N Al-Janabi, C S Salamao, D N Ross
Journal: Thorax (1975)

Sixteen frame-mounted fascia lata valves removed from the mitral, aortic or--in one patient--pulmonary position have been detailed histologically. These valves had remained in 15 patients (11 men and four women) for periods varying between 10 and 44 months. The reason for the original transplantation was either chronic rheumatic endocarditis or calcific aortic disease. In the mitral position, the leaflet in position nearest the site of the original anterior mitral valve cusp showed the least changes. The remaining two leaflets of the fascia lata valve in the mitral position, as well as those removed from the aortic or pulmonary position, showed more severe changes; these consisted of degeneration of collagen tissue and often a severe decrease of nuclei belonging to the fibroblastic series. These changes, as well as superimposition of fibrin or fibrous tissue, tended to become more pronounced the longer the valve had remained in the patient. Viability studies in valves removed from two patients have also been undertaken showing very greatly reduced activity. The possible causes for valve dysfunction have been reviewed, and the findings in this study suggest that contraction of fibrous tissue, which sandwiches the fascia lata valve cusps, may contribute to failure of satisfactory valve function. It is concluded that fascia lata forms a poor substitute for replacement of diseased cardiac valves.
Abdominal Aortic Aneurysms-Reply
Authors: Leslie W. Ottinger
Journal: JAMA (1975)

In Reply—  Angiography, when it can be done with minimal risk, is of value in determining the extent of an aneurysm and the degree of involvement of the aorta and its major branches by occlusive disease. Its use is justified before many, if not all, elective resections of abdominal aortic aneurysms, but it is not usually necessary when the question is one of size alone. When the absence of calcium and other characteristics prevents visualization of aneurysms on plain x-ray films, ultrasonography provides a useful alternative. The importance of the physical examination and plain x-ray films was stressed not because they are the only methods but because they are the most available. Dr Dixon's comments are quite correct.
The Low-Tryptophan Diet In Psoriasis
Authors: Richard M. Caplan
Journal: JAMA (1969)

<h3>To the Editor:—</h3> It seems unfortunate that the negative report by Drs. Petrozzi and Rosenbloom (<b>205</b>:345, 1968), "Low-Tryptophan Diet in Treatment of Psoriasis," did not actually include patients on a genuine low-tryptophan diet. "Turkey-Meat Diet in Treatment of Psoriasis" would have been more relevant. Their laboratory confirmation of the true tryptophan content of turkey meat, plus clinical reports, help consign to limbo the notion of therapeutic efficacy of turkey meat in psoriasis. Whether a true low-tryptophan diet would help is still unsettled. Carruthers (<i>Med J Aust</i><b>1</b>:493, 1968) reported it highly useful in 12 patients, but the circumstances were uncontrolled. One outpatient of mine, who was willing to subject himself to a three-week trial of that diet, had no benefit.
595 Evidence for eradication of HCV, assessed with transcription mediated amplification (TMA), in chronic hepatitis C patients with sustained virological response to therapy
Authors: S. Maylin, M. Martinot-Peignoux, N. Boyer, M.P Ripault, C. Féray, M.H. Nicolas-Chanoine, P. Marcellin
Journal: Journal of Hepatology (2006)
The Risk of Vaccination — The Importance of “Negative” Studies
Authors: Bruce G. Gellin, William Schaffner
Journal: New England Journal of Medicine (2001)

Falsehood flies and the truth comes limping after; so that when men come to be undeceived it is too late: the jest is over and the tale has had its effect.— Jonathan Swift1 Despite their success in the control and elimination of serious infectious diseases around the globe, vaccines are increasingly the focus of controversy rather than compliments. Concern about adverse effects — real and otherwise — has accompanied vaccines since the first uses of smallpox vaccine.2 Yet skepticism about vaccines has flourished in our postmodern society, with its distrust of science, its increased attention to risk, and its . . .
Hearing restoration: Graeme Clark, Ingeborg Hochmair, and Blake Wilson receive the 2013 Lasker~DeBakey Clinical Medical Research Award
Authors: Corinne Williams
Journal: Journal of Clinical Investigation (2013)

Living in a world of silence can be isolating and lonely for those who have lost their hearing or were born deaf. When results from early seminal studies provided hope that a device could restore hearing to the deaf through electrical stimulation of the auditory nerve, many experts adamantly disagreed that hearing could be restored in a meaningful way. Fortunately, many dedicated individuals ignored these detractors and committed themselves to the development of such a device. The 2013 Lasker∼DeBakey Clinical Medical Research Award honors Graeme Clark, Ingeborg Hochmair, and Blake Wilson (Figure ​(Figure1),1), three visionaries who have contributed greatly to development of the modern cochlear implant. This device has brought a world of sound and improved the quality of life for hundreds of thousands of people since its inception. 



Figure 1

The recipients of the 2013 Lasker∼DeBakey Clinical Medical Research Award.
Signs and Symptoms in Pediatrics
Authors: Hugh A. Carithers
Journal: JAMA (1983)

The author well expresses his intention in the preface of this worthy reference book for physicians whose special interest is the care of infants and children: This book is a distillation of lists, designed to help in the retrieval of stored bits of information from the cerebral recesses. In such a venture, success or failure depends on thoroughness, usefulness, and manner of presentation.  The contents cover wide-ranging possibilities for the causes of signs and symptoms associated with medical problems, but as the author states, Obviously, there are signs and symptoms other than those presented in this book; only the common ones, interspersed with some seen less frequently, have been included. It was disappointing to find that the section on skin occupies only 24 of the book's 654 pages, with no list to help unravel the tangle and define the problem of so many of the rashes seen in childhood diseases.
Splenic Rupture Due to Improper Placement of Automobile Safety Belt
Authors: William M. Cocke, Kenneth K. Meyer
Journal: JAMA (1963)

WIDESPREAD USE of seat belts has resulted in a pronounced reduction of major and fatal injuries from automobile crashes.<sup>1-5</sup>However, if improperly positioned, seat belts may cause severe injury. In the case here presented, the belt was positioned so that the impact of the collision, plus the restraining action of the belt when the patient's body was thrown forward, caused sudden, severe compression of the upper abdominal viscera, with subsequent rib fractures and splenic rupture. This is believed to be the first reported case of splenic rupture caused by a lap-type automobile seat belt. <h3>Report of a Case</h3> A short, stocky 62-yr-old woman was a passenger in the front seat of an automobile which struck another automobile broadside at 35 mph. The driver, wearing no seat belt, was uninjured. When brought to the Ochsner Foundation Hospital Emergency Room, the patient complained of discomfort in the abdomen and left flank
Open access gastroscopy: second survey of current practice in the United Kingdom.
Authors: J G Silcock, M G Bramble
Journal: Gut (1997)

In June 1990 a survey of members of the endoscopy section of the British Society of Gastroenterology showed that 47% of respondents were offering some form of open access gastroscopy (OAG). Only 10% offered true (non-censored) OAG. The survey was repeated in June 1994. The overall provision of OAG had risen to 74%, most of whom were offering true OAG. Censored OAG is still widely practised and characterised by referral letters to a consultant in contrast with the use of referral forms (p &lt; 0.001). Referral forms are being increasingly used and are an effective way of capturing important data such as the patients9 symptoms (100%), previous treatment (87%), non-steroidal anti-inflammatory drug or aspirin use (78%), suspected diagnosis (74%), and other medical conditions (72%). Forms were used to establish clinical responsibility with the general practitioner in 64% of units. Standardised referral and reporting forms were used by 27% of respondents. A perceived inability to cope with the expected workload was still the most commonly cited reason for not being able to offer OAG. Although 20% of units with a single handed endoscopist were able to offer OAG, this compared with 68% of units with two or more endoscopists (p &lt; 0.001). Only three units indicated that an OAG service had had to be withdrawn, but a further 12 consultants (nine units) were now offering an age restricted service because of excessive workload. Two thirds of the respondents not offering OAG were hoping to do so in the near future. True OAG has increased from 10% to 41% in four years.
Scintigraphic evaluation and prognosis of patients with Reiter's syndrome.
Authors: A S Russell, M J Butler, B C Lentle
Journal: Annals of the Rheumatic Diseases (1979)

Knowledge of the association of Reiter's syndrome (RS) with the genetic marker HLA-B27 has not only given us a useful diagnostic tool but has also heightened our awareness of the association of this disease with ankylosing spondylitis (AS).This association has been recognised clinically for very many years.134A number of authors thought that under these circumstances AS could be regarded as a complication of RS.The proportion of such patients recognised depends on the duration of follow-up but could well be of the order of 25 %.0/0This figure is very similar to the reported prevalence of sacroiliitis seen on screening B27-positive blood donors.54It
Medicare is likely to pay for anticancer drugs
Authors: F. Charatan
Journal: BMJ (2002)

The US Congress looks set to provide cover for anticancer drugs under Medicare, the federal health insurance programme for Americans aged over 65.

A bill currently before the house looks likely to be passed this year. According to law makers and lobbyists, this would be a first step towards a prescription drug benefit for Medicare subscribers.

A compromise on drugs to treat cancer would help many elderly Americans who must often choose between expensive prescription drugs and groceries. More than a fifth of the 40 million Medicare beneficiaries …
A Case of Non-Malignant Pyloric Obstruction: Dilatation of the Pyloric Orifice: Recovery
Authors: R. Hagyard
Journal: BMJ (1887)

the subject of this paper, first came under my notice about five years ago, when she was Complaining of symptoms of gastric disturbance, such as one meets with in ordinary dyspepsia.She was at this time being attended by Dr. Fitzsimons, of York, who prescribed the ordinary stomachics.Her symptoms varied somewhat with the treatment, and she felt better some days than on others.About two years ago she commenced to vomit large quantities of food at in- tervals of a few days.I was then led to make an examination of the abdomen, the stomach being, found to be somewhat dilated, but no appearance of any abnormal growth could be detected in any of the regions of the abdomen.The vomit was examined, but no sarcinae or blood could be detected ; the material ejected was intensely acid.Owing to the patient living some distance away, I did not again see her for some months, when I fouind her greatly emaciated; the dila- tation of the stomach had extended, and the quantity of fluid vomited was much larger than formerly.The stomach was again examined, but no hardness or thickening near the pylorus could be detected.She was now taught to wash out her own stomach daily with a long tube and funnel after the manner advised by Dr. Clifford Allbutt, which process gave her considerable relief.In December last she appeared to be thinning rapidly, and from the nature of the cointents of the stomaeh that came away with the wash- ings out, I conteluided that very little food was finding its way into the intestine.She was now fed with Slinger's nutritive suppositories asid nutritive enemata, which appeared to keep up lher strength for some time, till, in February last, the rectum became irritable, and it was with difficulty that a small enema could be retained.The injection of a few drops of a 4 per cent.solution of ciicaine into the rectum somewhat lessened the irritability.During the whole of this time, she never once recollects noticing any blood in the vomit, and taking this point into consideration, as well as her family and previous history, which I will now relate, I came to the conclusion that the obstruction, whatever it might be, did not appear to be ma- lignant.Family and Personal Ilistory.-Herparenits are both dead, her father dyiDg fromi apoplexy, and her mother from bronchitis, both over 70 years of age.All her brothers and sisters are strong and
Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice
Authors: Stacey R Dillon, Cindy Sprecher, Angela Hammond, Janine Bilsborough, Maryland Rosenfeld-Franklin, Scott R Presnell, Harald S Haugen, Mark Maurer, Brandon Harder, Janet Johnston, Susan Bort, Sherri Mudri, Joseph L Kuijper, Tom Bukowski, Pamela Shea, Dennis L Dong, Maria Dasovich, Francis J Grant, Luann Lockwood, Steven D Levin, Cosette LeCiel, Kim Waggie, Heather Day, Stavros Topouzis, Janet Kramer, Rolf Kuestner, Zhi Chen, Don Foster, Julia Parrish-Novak, Jane A Gross
Journal: Nature Immunology (2004)
Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest
Authors: Leslie Smith, Shu Jing Liu, Lisa Goodrich, David Jacobson, Catherine Degnin, Nicole Bentley, Antony Carr, Gail Flaggs, Kathleen Keegan, Merl Hoekstra, Mathew J. Thayer
Journal: Nature Genetics (1998)
Touching up antibodies prevents autoimmunity
Authors: Mitch Leslie
Journal: The Journal of Experimental Medicine (2008)

Like the first draft of a term paper, the antibody genes of some B cells require revisions. On page 2985, Panigrahi et al. show that this genetic editing is faulty in patients with two kinds of autoimmune disease. The results could lead to new tests and refined treatments for these diseases.






Figure 1

Patients with lupus and type I diabetes have fewer rearrangements in the RS region—a marker of receptor editing.




During development in the bone marrow, maturing B cells reshuffle their antibody genes to fashion defenses against a wide variety of pathogens. But these rearrangements can also yield antibodies that target self antigens and provoke autoimmune diseases. To forestall misdirected attacks, self-targeting B cells often undergo further recombination, known as receptor editing, which reshapes their antibody genes.

But receptor editing seems to falter in B cells from patients with autoimmune diseases, Panigrahi et al. report. The researchers gauged the amount of rearrangement in a DNA segment called RS. Although RS doesn't code for part of the antibody, rearrangements there reflect the cell's attempts to fix potentially dangerous antibody genes by reshuffling nearby coding segments. About 30% of patients with lupus or type I diabetes exhibited abnormally low amounts of RS rearrangement, the researchers found. This reduced level of editing might allow self-reactive B cells to escape correction and lead to autoimmune attacks.

Immune tolerance can break down at several points, and reduced receptor editing points to a flaw that develops before B cells exit the bone marrow. Current autoimmune treatments that temporarily deplete B cells are less likely to work in patients with such early-arising problems, the researchers suggest, because the number of self-attacking B cells might quickly rebound. Thus, measuring levels of RS rearrangement might help doctors tailor treatments for patients and allow earlier identification of people prone to autoimmunity.
Doctors with problems in an NHS workforce
Authors: L J Donaldson
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objectives</b>: To describe the incidence, nature, and implications of serious disciplinary problems among the medical staff of a large NHS hospital workforce. Design - Descriptive study with analysis of case records. <b>Setting</b>: Northern Health Region, an administrative area within the NHS covering a population of three million. <b>Subjects</b>: Forty nine hospital doctors: 46 consultants and three associate specialists. <b>Main outcome measures</b>: The nature of the problems encountered within the doctors9 practice, and the types of action taken by the employing authority. <b>Results</b>: Over a five year period concerns serious enough to warrant the consideration of disciplinary action were raised about 6% of all senior medical staff (49/850). Ninety six types of problem were encountered, and were categorised as poor attitude and disruptive or irresponsible behaviour (32), lack of commitment to duties (21), poor skills and inadequate knowledge (19), dishonesty (11), sexual matters (seven), disorganised practice and poor communication with colleagues (five), and other problems (one). Twenty five of the 49 doctors retired or left the employer9s service, whereas 21 remained in employment after counselling or under upervision <b>Conclusions</b>: Existing procedures for hospital doctors within the NHS are inadequate to deal with serious problems. Dealing with such problems requires experience, objectivity, anda willingness to tolerate unpleasantness and criticism. Because most consultants9 contracts are now held by NHS trust hospitals, however, those who had developed skill over the years in handling these complex issues are now no longer involved.