tbuckley/cabot-search huggingface dataset:
Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients
Authors: Lukas Baitsch, Petra Baumgaertner, Estelle Devêvre, Sunil K. Raghav, Amandine Legat, Leticia Barba, Sébastien Wieckowski, Hanifa Bouzourene, Bart Deplancke, Pedro Romero, Nathalie Rufer, Daniel E. Speiser
Journal: Journal of Clinical Investigation (2011)

In chronic viral infections, CD8+ T cells become functionally deficient and display multiple molecular alterations. In contrast, only little is known of self- and tumor-specific CD8+ T cells from mice and humans. Here we determined molecular profiles of tumor-specific CD8+ T cells from melanoma patients. In peripheral blood from patients vaccinated with CpG and the melanoma antigen Melan-A/MART-1 peptide, we found functional effector T cell populations, with only small but nevertheless significant differences in T cells specific for persistent herpesviruses (EBV and CMV). In contrast, Melan-A/MART-1–specific T cells isolated from metastases from patients with melanoma expressed a large variety of genes associated with T cell exhaustion. The identified exhaustion profile revealed extended molecular alterations. Our data demonstrate a remarkable coexistence of effector cells in circulation and exhausted cells in the tumor environment. Functional T cell impairment is mediated by inhibitory receptors and further molecular pathways, which represent potential targets for cancer therapy.
Central modulation of pain
Authors: Michael H. Ossipov, Gregory O. Dussor, Frank Porreca
Journal: Journal of Clinical Investigation (2010)

It has long been appreciated that the experience of pain is highly variable between individuals. Pain results from activation of sensory receptors specialized to detect actual or impending tissue damage (i.e., nociceptors). However, a direct correlation between activation of nociceptors and the sensory experience of pain is not always apparent. Even in cases in which the severity of injury appears similar, individual pain experiences may vary dramatically. Emotional state, degree of anxiety, attention and distraction, past experiences, memories, and many other factors can either enhance or diminish the pain experience. Here, we review evidence for “top-down” modulatory circuits that profoundly change the sensory experience of pain.
A Peripherin/Retinal Degeneration Slow Mutation (Pro-210-Arg) Associated with Macular and Peripheral Retinal Degeneration
Authors: Michael B. Gorin, Kelly E. Jackson, Robert E. Ferrell, Val C. Sheffield, Samuel G. Jacobson, J. Donald M. Gass, Elysey Mitchell, Edwin M. Stone
Journal: Ophthalmology (1995)

Background: Mutations in the peripherin/retinal degeneration slow (RDS) gene have been identified in patients with retinitis pigmentosa and pattern macular dystrophy.The authors initially examined a large family affected with both peripheral and macular degeneration, inherited as an autosomal dominant trait.Screening for peripherin/RDS mutations identified a previously unreported nucleotide alteration in all of the affected individuals.Two additional families later were found to have this same mutation.Methods: DNA samples from the members of three unrelated families were screened for peripherin/RDS mutations by denaturing gradient gel electrophoresis of the polymerase chain reaction-amplified peripherin/RDS coding sequences.The sequence change that was detected was further characterized by DNA sequencing.Family members were examined and evaluated with psychophysical and electrophysiologic methods.Results: A proline to arginine mutation in codon 210 of peripherin/RDS was found in all clinically affected individuals.Macular changes included extensive geographic atrophy, pigment epithelial changes, and/or drusen.The proline to arginine mutation was not found among 100 healthy individuals, making it unlikely to be a nondisease-causing polymorphism.Conclusions: The authors identified a novel peripherin/RDS gene mutation associated with autosomal dominant retinal degeneration in patients from three different families.The largest family showed a broad variability in the expressivity of the mutation.The overlap of clinical features with those of age-related maculopathy highlights the need to consider photoreceptor-specific genes as potential factors in the etiology of the latter condition.
Smoking and Death Rates--Report on Forty-Four Months Of Follow-up of 187,783 Men
Authors: E. C. Hammond, D. Horn
Journal: CA A Cancer Journal for Clinicians (1988)

The death rates from specific causes have been studied in relation to smoking habits in a group of /87,783 men between the ages ofSO and 69.During the period of the study 11,870 of these men died.For micro scopically proved cases of cancer as well asfor the total cases reported as cancer, it wasfound that the death rates were higher among regular cigarette smokers than among men who never smoked, that the mortality ratio increased with the number of cigarettes smoked per day, and that the death rates were higher among pipe and
A cute plasma ghrelin and leptin responses to oral feeding or intraperitoneal hypertonic glucose-based dialysate in patients with chronic renal failure
Authors: Miguel Perez-Fonten, Fernando Cordido, Ana Rodreguez-Carmona, Rafael Garcea-Naveiro, MareA Luisa Isidro, Pedro Villaverde, JeseS Garcea-Buela
Journal: Kidney International (2005)
Reporting of Informed Consent and Ethics Committee Approval in Clinical Trials
Authors: Veronica Yank
Journal: JAMA (2002)

ASSOCIAtion issued the Declaration of Helsinki in 1964, 1 with subsequent updates, 2 to establish international regulations for human experimentation.It specifically identified 2 protections: that all participants in trials should understand the risks, benefits, and alternatives of the experiment and, following this, should enroll in the trial under their own free will, by giving informed consent, and that a disinterested party unconnected with the trial, termed the ethics committee or institutional review board, should have approved the experimental protocol after assuring its appropriateness of design.When publishing reports of experimentation, journals have an obligation to define what constitutes medical research of the highest quality and to make the ethical conduct of trials a part of this definition.The Declaration of Helsinki charges journals with this important responsibility, stating: "Publishers have ethical obligations. . . .Reports of experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication." 2 It is essential that journals inform the public that, to the extent they can determine, the trials they publish are ethical.They can do so in part by requiring that all published trials describe informed consent and ethics committee approval.This duty is supported by the International Committee of Medical Journal Editors (ICMJE). 36][7][8] Data at the time 5 and further documented since 9 suggested that articles reporting ethical protections were of higher methodologic quality than those that did not.The current study assesses whether journals have improved in their reporting of ethical protections from the time these deficiencies were highlighted. METHODSClinical trials were studied because their use of interventions makes the reporting of safeguards particularly important.We selected a random sample of trials published in the 18 months before and after 1997 (
An Evaluation of the Efficacy of Methods Used in Screening for Lower-Limb Arterial Disease in Diabetes: Response to Williams et al.
Authors: Alfred Janssen, Ernst Chantelau
Journal: Diabetes Care (2006)

studies are usually appropriate, but realistically speaking, why would industry fund studies that have an excellent chance of showing what a number of smaller studies have already shown, especially since they are making a lot of money in that market already?And, if a larger study were negative, wouldn't there be cries to do even larger ones?After all, one can really never prove a negative.There is always the possibility that another slight twist or an even larger study could be positive.If it takes a very large number of subjects to show a significant positive result, the clinical benefit must be difficult to uncover.At some point, one has to conclude that enough is enough and we have to accept the results at hand.In the meantime, large amounts of money are being diverted from better uses in our health care system.
Abstract 5459: Antitumor activity of EP80061, a small-glyco drug in preclinical studies
Authors: Vanessa Nancy-Portebois, Eric Cabannes, Maurice Petitou, Guillaume Serin, Jean-François Mirjolet
Journal: Cancer Research (2010)

Abstract Background: Heparan sulphate (HS) containing proteoglycans regulate the activity of many proteins (growth factors, cytokines, adhesion molecules…) involved in pathologies like cancer, inflammation, cardiovascular, metabolic and neurodegenerative diseases, as well as in viral infection. HS mimicking oligosaccharides can interfere with protein/HS interactions and thus modulate the resulting biological effects. The optimization of fully synthetic HS mimetics exhibiting anti-tumour and anti-metastatic properties is currently in progress. Methods: Compound selection was performed using classical in vitro assays (binding and proliferation) and a cellular angiogenesis assay (Angiokit®). In vivo, Swiss nude mice subcutaneously (SC) xenografted with A-673 human rhabdomyosarcoma tumor cells were used to compare compounds showing significant anti-tumour activity. Compounds were intraperitonealy (IP) injected on a daily basis. The most potent compound was then evaluated on syngeneic mouse models: C57 BL/6 mice intravenously (IV) injected with B16-F10 malignant melanoma cells and Balb/c mice bearing orthotopic (OT) Renca kidney carcinoma. Results: Binding assays to FGF-2, PDGF-BB, VEGF-B and SDF-1α in Biacore experiments and growth factor-dependent proliferation tests led to the identification of several inhibitors. Optimized compounds exhibiting anti-angiogenic activities were selected in Angiokit® assays. EP80061 was selected for further studies on the basis of significant activity in this assay. In A-673 SC mouse model, EP80061 was also the most powerful compound. When IP injected at 30 mg/kg/inj. for 28 consecutive days, it induced a marked tumour growth delay. At D22, the optimal T/C value (46%) was reached with a significantly lower tumour volume (p=0.0006, 1672 ± 760 and 765 ± 402 mm3 for vehicle and EP80061 treated mice, respectively). EP80061 induced also a very significant decrease in lung metastasis development in B16-F10 IV injected mice treated at 30 mg/kg/inj. (p&amp;lt;0.0001, 92 ± 24 and 12 ± 8 metastases for vehicle and EP80061 treated mice, respectively). Promising results were also obtained on OT Renca bearing mice where EP80061 induced a decrease of OT tumour size. Conclusion: Current preclinical results support EP80061 as a lead candidate for further developments of small-glyco drugs as anticancer compounds. 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 5459.
2011 ACCF/AHA/HRS Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
Authors: Valentin Fuster, Lars E. Rydén, Davis S. Cannom, Harry J. Crijns, Anne B. Curtis, Kenneth A. Ellenbogen, Jonathan L. Halperin, G. Neal Kay, Jean-Yves Le Huezey, James E. Lowe, S. Bertil Olsson, Eric N. Prystowsky, Juan Luis Tamargo, L. Samuel Wann
Journal: Circulation (2011)

Atrial Flutter . . . . . .
Selective Utilization of Toll-like Receptor and MyD88 Signaling in B Cells for Enhancement of the Antiviral Germinal Center Response
Authors: Baidong Hou, Philippe Saudan, Gary Ott, Matthew L. Wheeler, Ming Ji, Lili Kuzmich, Linda M. Lee, Robert L. Coffman, Martin F. Bachmann, Anthony L. DeFranco
Journal: Immunity (2011)
REMARKS ON ONE HUNDRED ABDOMINAL SECTIONS.
Authors: BYRON ROBINSON
Journal: JAMA (1894)

The typical "control" laparotomy is prepared for three days by administering salts and calomel, until a dozen bowel movements are produced or until the uile glistens in the stool. The patients should then rest in bed and be given no purgatives. This will allow the fermenting gas to escape and when the ablomen is opened on the fifth day the intestines will De collapsed like ribbons. Such a course of preparatory treatment is wise as it stimulates all the alimentary glands to the highest stage of depletion. The pores of the skin are opened and stimulated to secretion by daily baths. At the time of the operation all the secretive tissue is at its highest tension md the depleting avenues are all washed out and open. Pure ether was used as an anesthetic in about 90 per cent. of cases and though it may be followed by oronchitis and nephritis,
A sacrificial lamb
Authors: J. Bahrami
Journal: BMJ (1999)

The General Medical Council's press release of 10December 1998told the waiting public of the case of the first doctor who had been suspended by the GMC because of incompetence(2January, p2). This unfortunate doctor was a general practitioner registrar in Yorkshire. Not surprisingly, as the director of postgraduate general practice education for Yorkshire, I was soon inundated by telephone calls from reporters of medical as well as non-medical newspapers. But all they wanted to know were the gory details of the case. How many patients had been harmed? Why did we take so long to act? What is the doctor's home address? Can we have a picture of him?

I was annoyed and even angry with the way that the …
Quantifying Pulmonary Inflammation in Cystic Fibrosis with Positron Emission Tomography
Authors: Delphine L. Chen, Thomas W. Ferkol, Mark A. Mintun, Jessica E. Pittman, Daniel B. Rosenbluth, Daniel P. Schuster
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Although infection contributes to morbidity in patients with cystic fibrosis (CF), the host inflammatory response is also an important cause of progressive pulmonary function deterioration. Quantifying the inflammatory burden in these patients is challenging and often requires invasive procedures. Positron emission tomographic imaging with [18F]fluorodeoxyglucose ([18FDG]) could be used as a noninvasive alternative to quantify lung inflammation.Objective: To determine the relationships among lung [18F]FDG uptake, bronchoalveolar lavage (BAL) neutrophil concentrations, and pulmonary function in patients with CF.Methods: Twenty patients and seven healthy volunteers were studied. A subset of seven patients also consented to undergo BAL. The uptake of [18F]FDG by the lungs was measured as the net influx rate constant Ki. Patients were stratified by rate of decline in pulmonary function into stable, intermediate, and rapidly declining groups. Ki was compared among groups and was correlated against neutrophil concentrations in BAL fluid.Results: Ki was significantly elevated (p < 0.05) among patients with CF as a whole compared with healthy control subjects (0.0015 ± 0.0009 versus 0.0007 ± 0.0002 ml blood/ml lung/min) but especially in patients with rapidly declining pulmonary function (0.0022 ± 0.0011 ml blood/ml lung/min). Ki correlated positively with the number of neutrophils present in BAL fluid.Conclusion: Imaging with [18F]fluorodeoxyglucose and positron emission tomography can be used to assess inflammatory burden in patients with CF. Elevations in Ki may be able to identify patients with more aggressive disease and may be useful in monitoring changes in inflammatory burden in response to novel treatments.
Two forms of reactive arthritis?
Authors: P. Toivanen, A. Toivanen
Journal: Annals of the Rheumatic Diseases (1999)

Inflammatory arthritides developing after a distant infection have so far been called reactive or postinfectious, quite often depending on the microbial trigger and/or HLA-B27 status of the patient. For clarity, it is proposed that they all should be called reactive arthritis, which, according to the trigger, occurs as an HLA-B27 associated or non-associated form. In addition to the causative agents and HLA-B27, these two categories are also distinguished by other characteristics. Most important, HLA-B27 associated arthritis may occur identical to the Reiter9s syndrome with accompanying uretheritis and/or conjunctivitis, whereas in the B27 non-associated form this has not been clearly described. Likewise, only the B27 associated form belongs to the group of spondyloarthropathies.
Purchase of Managed Care: Informed Consumers or a Distorted Market?-Reply
Authors: David F. Drake
Journal: JAMA (1997)

<h3>In Reply.</h3> —Dr Farrell may not have understood the full implications of "market dynamics" in the title of my article. Like "Old Man River," the dynamic of a market is just to keep rolling along, which is why Farrell is correct in describing managed care as "a distorted solution to a distorted market." However, most of the distortions in the structure of the health market are on the buyer side, not the provider side of the market. The lack of systematic assistance for improving consumer know-how in purchasing health services and the failure of employer-sponsored insurance to incorporate more directly consumer sensitivity to the costs of care are, I believe, the 2 principal remaining market shortcomings. Managed care has not contributed to solving either of these flaws. Instead of helping consumers become knowledgeable about purchasing health care service, it has restricted consumer choices of allowable providers and therapies. However, by making employees
Bronchoalveolar Lavage and Tracheal Aspirate for Assessing Airway Inflammation in Children
Authors: MICHAEL D. SHIELDS, JOSEF RIEDLER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Studies using bronchoalveolar lavage (BAL) and tracheal aspirate (TA) have increased our knowledge of the underlying airway inflammation present in the childhood disorders of asthma, cystic fibrosis (CF), and neonatal chronic lung disease (CLD) (1–6). A BAL sample is obtained by wedging a bronchoscope or catheter into a bronchus and isolating the distal airway. A volume of saline is instilled and the fluid aspirated back from the airway, using gentle suction. The aim of this process is to obtain aspirated fluid that will contain the microbes, cells, and noncellular constituents present in the epithelial lining fluid of the small airways and alveoli. Flexible fiberoptic bronchoscopy (FOB) allows a visual location and wedging of the bronchoscope tip (1, 7–12). In blind nonbronchoscopic BAL, a catheter is passed through an endotracheal tube and blindly wedged in a distal airway. This technique has been used to obtain normal cellular and noncellular constituents and to study diffuse airway inflammation (13–16). In neonatal studies, a TA or bronchial washing can be obtained by inserting a catheter through an endotracheal tube for a short distance (usually not wedged) and aspirating back mucus or instilled fluid. Darlow and coworkers (17) have shown that samples obtained by dry shallow suctioning, often used routinely to maintain airway patency in neonatal intensive care, may also provide adequate samples for research purposes. The mean values of dry and lavage samples were similar with respect to myeloperoxidase and a 1 -antitrypsin content.
THE TREATMENT OF ARTERIOSCLEROSIS.
Authors: J. M. ANDERS
Journal: JAMA (1904)

To develop the subject of the treatment of arteriosclerosis in its principal bearings, it will be necessary first to subdivide the cases into etiologic categories, as follows: 1. Those due to toxic agencies in the blood, e. g., in chronic alcoholism, lead poisoning, diabetes mellitus, syphilis, gout, rheumatism and other infectious diseases. 2. Arteriosclerosis caused by the constant ingestion of an excess of either the carbohydrates or nitrogenous foods. 3. Cases dependent on constant hypertension, due to muscular overexercise, as in certain laborious occupations and violent competitive sports. 4. Aortic rÃÂ©gurgitation, in which overfilling of the blood vessels is a concomitant; also exalted tension arising from ingestion of an excess of fluids, as in beer drinkers. 5. Cases due to senile degenerative changes. With the two last-mentioned groups of cases I shall not deal at present writing, although many of the measures that will be recommended for arteriosclerosis originating in
846-3 Potential impact of MADIT II and the centers for medicaid services criteria on care of patients diagnosed with myocardial infarction
Authors: Richard F Otten, Eva M Kline-Rogers, Jianming Fang, Darryl A Elmouchi, Aman Chugh, Firas Al-Marayati, Frank Pelosi, Kim A Eagle
Journal: Journal of the American College of Cardiology (2004)
COMPLETE INGUINAL EXTRAPERITONEAL HERNIA OF THE BLADDER; RECOVERY.
Authors: J. F. BALDWIN
Journal: JAMA (1901)

Mr. D. H., West Mansfield, Ohio, aged 51, 5 ft. 6 inches in height and weighing 245 lbs., consulted me May 26, 1900. He stated that he had had an inguinal rupture for eight years, which he had been unable to retain with any form of truss. Ordinarily he had been able to reduce his hernia, but it had now been irreducible for forty-eight hours. The day before he consulted his local physician, Dr. Wanser, who administered an anesthetic but was unable to affect a reduction. He stated that he had noticed many times that he was unable to empty his bladder completely without lifting up the tumor. The tumor was about the size of two fists and extended to the bottom of the scrotum. It was somewhat oval in outline and conveyed a sensation of fluctuation. It was tender and entirely irreducible. Although he was experiencing some pain, there
Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells
Authors: Robert Zeiser, Dennis B. Leveson-Gower, Elizabeth A. Zambricki, Neeraja Kambham, Andreas Beilhack, John Loh, Jing-Zhou Hou, Robert S. Negrin
Journal: Blood (2007)
Abstract 11074: Addition of Mesenchymal Stem Cells Enhances the Therapeutic Effects of Skeletal Myoblast Cell-Sheet Transplantation in a Rat Ischemic Cardiomyopathy Model
Authors: Yasuhiro Shudo, Shigeru Miyagawa, Hanayuki Ohkura, Satsuki Fukushima, Atsuhiro Saito, Naomasa Kawaguchi, Nariaki Matsuura, Tatsuya Shimizu, Teruo Okano, Akifumi Matsuyama, Yoshiki Sawa
Journal: Circulation (2011)

Introduction: The use of cell sheets for transplanting skeletal myoblasts (SMBs) into the heart has been shown to effectively deliver functional SMBs, thereby inducing a functional recovery of isch...