tbuckley/cabot-search huggingface dataset:
ON THE NUMBER AND NATURE OF ANTIGEN-SENSITIVE LYMPHOCYTES IN THE BLOOD OF DELAYED-HYPERSENSITIVE HUMAN DONORS
Authors: Luis Jimenez, Barry R. Bloom, Myron R. Blume, Herbert F. Oettgen
Journal: The Journal of Experimental Medicine (1971)

The virus plaque assay has been successfully employed to enumerate antigen-sensitive cells in the peripheral blood lymphocyte populations of tuberculin-hypersensitive human donors. The method is based on the finding that, while resting lymphocytes are unable to produce a variety of viruses upon infection, lymphocytes activated by specific antigens become capable of virus replication. The average number of antigen-sensitive cells detected in cell populations from donors reacting to first test strength or intermediate test strength tuberculin was approximately 3.6/1000 lymphocytes, and the averages for both groups were similar. Studies on the kinetics of appearance of these virus plaque-forming cells and on the effects of the mitotic inhibitor, vinblastine, indicate that the activation of these antigen-sensitive cells is a linear process and that the cells must be nondividing cells during this process. These qualities contrast markedly with those described for the mitogenic response and the antibody-producing cells which require cell division and increase exponentially. On the basis of these experiments it is suggested that the antigen-sensitive cell measured in the virus plaque assay is the effector cell in delayed-type hypersensitivity reactions and, in addition, may be one of the cells critically involved in antibody formation.
Dutch doctors call for EU evaluation of cost effectiveness of high cost orphan drugs
Authors: T. Sheldon
Journal: BMJ (2012)

<h3>Abstract</h3> Synaptic plasticity involves structural modifications in dendritic spines. Increasing evidence suggests that structural plasticity is modulated by local protein synthesis and actin remodeling in a synapsis-specific manner. However, the precise molecular mechanisms connecting synaptic stimulation to these processes in dendritic spines are still unclear. In the present study, we demonstrate that the configuration of phosphorylation sites in eEF1A2, an essential translation elongation factor in neurons, is a key modulator of structural plasticity in dendritic spines. A mutant that cannot be phosphorylated stimulates translation but reduces actin dynamics and spine density. By contrast, the phosphomimetic variant loosens its association with F-actin and becomes inactive as a translation elongation factor. Metabotropic glutamate receptor signaling triggers a transient dissociation of eEF1A2 from its GEF protein in dendritic spines, in a phospho-dependent manner. We propose that eEF1A2 establishes a crosstalk mechanism that coordinates local translation and actin dynamics during spine remodeling.
Opiate-mediated inhibition of calcium signaling is decreased in dorsal root ganglion neurons from the diabetic BB/W rat.
Authors: K E Hall, A A Sima, J W Wiley
Journal: Journal of Clinical Investigation (1996)

The effect of diabetes mellitus on opiate-mediated inhibition of calcium current density (I(D Ca) [pA pF-1]) and cytosolic calcium response ([Ca2+]i nM) to depolarization with elevated KCl and capsaicin was assessed. Experiments were performed on isolated, acutely dissociated dorsal root ganglion (DRG) neurons from diabetic, BioBreeding/Worcester (BB/W) rats and age-matched control animals. Sciatic nerve conduction velocity was significantly decreased in diabetic animals compared to controls. Mean I(DCa) and [Ca2+]i responses to capsaicin and elevated KCl recorded in DRGs from diabetic animals were significantly larger than those recorded in DRG neurons from controls. In neurons from diabetic animals, the opiate agonist dynorphin A (Dyn A; 1, 3, and 5 microM) had significantly less inhibitory effect on I(D Ca) and KCl-induced [Ca2+]i responses compared to controls. Omega-conotoxin GVIA (omega-CgTX; 10 microM) and pertussis toxin (PTX; 250 ng ml-1) abolished Dyn A-mediated inhibition of I(DCa) and [Ca2+]i in control and diabetic neurons, suggesting that Dyn A modulated predominantly N-type calcium channels coupled to opiate receptors via PTX-sensitive (Gi/o) inhibitory G proteins. These results suggest that opiate-mediated regulation of PTX-sensitive, G protein-coupled calcium channels is diminished in diabetes and that this correlates with impaired regulation of cytosolic calcium.
The Virus Hypothesis in Systemic Lupus Erythematosus
Authors: PAUL E. PHILLIPS
Journal: Annals of Internal Medicine (1975)

Type-C viruses are currently the prime etiologic candidates in systemic lupus erythematosus. On the basis of knowledge gained from studies of experimental and human models of chronic viral disease, there are possible pathogenetic roles of a virus in systemic lupus erythematosus. Experimental attempts at implicating specific viruses have been predominantly negative, but evidence for enhanced type-C-virus expression has recently been reported.
Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD)/ribavirin
Authors: Peter Ferenci, Michael W. Fried, Mitchell L. Shiffman, Coleman I. Smith, George Marinos, Fernando L. Gonçales, Dieter Häussinger, Moises Diago, Giampero Carosi, Daniel Dhumeaux, Antonio Craxì, Monique Chaneac, K. Rajender Reddy
Journal: Journal of Hepatology (2005)
Ga-67 Uptake in Cutaneous B-Cell Lymphoma
Authors: GHADA S. ASSASSA, MICHAEL E. SIEGEL, DAVID C. P. CHEN, AZIZULLAH ANSARI
Journal: Clinical Nuclear Medicine (1994)

Cutaneous B cell lymphoma is not commonly seen and occurs in only 8.2% of non-Hodgkins lymphoma. Although Ga-67 uptake by cutaneous T cell lymphoma has been reported, the literature on Ga imaging in cutaneous, B cell lymphoma is limited. The authors report the gallium scan and clinical findings on 2 cases of cutaneous B cell lymphoma.
Inflammatory Biomarkers and Comorbidities in Chronic Obstructive Pulmonary Disease
Authors: Mette Thomsen, Morten Dahl, Peter Lange, Jørgen Vestbo, Børge G. Nordestgaard
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Patients with chronic obstructive pulmonary disease (COPD) have evidence of systemic inflammation that may be implicated in the development of comorbidities.Objectives: To test the hypothesis that elevated levels of three inflammatory biomarkers are associated with increased risk of comorbidities in COPD.Methods: We examined 8,656 patients with COPD from two large Danish population studies and during a median 5 years' follow-up recorded hospital admissions due to major comorbidities as endpoints.Measurements and Main Results: We measured baseline C-reactive protein (CRP), fibrinogen, and leukocyte count, and recorded admissions due to ischemic heart disease, myocardial infarction, heart failure, type II diabetes, lung cancer, pneumonia, pulmonary embolism, hip fracture, and depression for all participants. Multifactorially adjusted risk of ischemic heart disease was increased by a factor of 2.19 (95% confidence interval, 1.48–3.23) in individuals with three biomarkers elevated (CRP > 3 mg/L, fibrinogen > 14 μmol/L, and leukocyte count > 9 × 109/L) versus individuals with all three biomarkers at or below these limits. Corresponding hazard ratios were 2.32 (1.34–4.04) for myocardial infarction, 2.63 (1.71–4.04) for heart failure, 3.54 (2.03–6.19) for diabetes, 4.00 (2.12–7.54) for lung cancer, and 2.71 (2.03–3.63) for pneumonia. There were no consistent differences in risk of pulmonary embolism, hip fracture, or depression as a function of these three biomarkers.Conclusions: Simultaneously elevated levels of CRP, fibrinogen, and leukocyte count are associated with a two- to fourfold increased risk of major comorbidities in COPD. These biomarkers may be an additional tool for clinicians to conduct stratified management of comorbidities in COPD.
Medicare-Designated Centers for Cardiac Transplantation
Authors: Dale G. Renlund, Michael R. Bristow, Merlin R. Lybbert, John B. O'Connell, William A. Gay
Journal: New England Journal of Medicine (1987)

On June 27, 1986, the U.S. Department of Health and Human Services (HHS) announced that Medicare would soon begin to provide reimbursement for heart transplantations.1 Although HHS is to be commended for recognizing the nonexperimental nature of these procedures, despite their inherent cost, and for attempting a rational matching of national resources with the needs of U.S. citizens,2 , 3 this landmark decision is certain to generate lively debate both within and outside the medical community.The purpose of this article is not to debate the correctness of the HHS decision but rather to address how regulation should best be implemented. The . . .
UK announces cash boost for vaccines and free health care in poor countries
Authors: G. Yamey
Journal: BMJ (2010)

The UK government announced last week that it will invest £150m (€165m; $230m) over 10 years in the Global Alliance for Vaccines and Immunisation (GAVI) and £5m to launch a centre of expertise to help countries provide free health care.

The announcement, made at a meeting at the UK Department for International Development of experts in global health and development, comes amid growing concern in the global health community that the United Nations’ millennium development goals on child and maternal health (goals 4 and 5) will not be met without concerted global action ( BMJ 2010;340:c431, doi: 10.1136/bmj.c431).

The United Nations Development Programme has been studying progress on these goals in 30 countries, and its final report will be published shortly. Its study, discussed at the meeting, found that only seven countries are on track to reach the …
European Community research on environmental mutagenesis and carcinogenesis.
Authors: A I Sors
Journal: Environmental Health Perspectives (1993)

Within the 12 Member States of the European Community (EC), environmental policy is now formulated primarily at Community level. As a result, the EC has important regulatory responsibilities for the protection of workers, consumers, and the general public from risks that may arise from environmental chemicals, foremost among them potential carcinogens and mutagens. An important part of EC environmental research and development is intended to provide a scientific basis for these regulations as well as increasing understanding of the basic mechanisms involved in environmental carcinogenesis and mutagenesis. This paper contains a brief introduction to EC environment policy and research, followed by an overview of EC chemicals control activities that are of particular relevance to the research and development program. Community-level research on environmental mutagenesis and carcinogenesis is then reviewed in some detail, including the achievements of recent projects, the scientific content of the current program, and perspectives for the future.
Mature parasite-infected erythrocyte surface antigen (MESA) of Plasmodium falciparum binds to the 30-kDa domain of protein 4.1 in malaria-infected red blood cells
Authors: Karena L. Waller, Wataru Nunomura, Xiuli An, Brian M. Cooke, Narla Mohandas, Ross L. Coppel
Journal: Blood (2003)
Population-Based Molecular Screening for Lynch Syndrome: Implications for Personalized Medicine
Authors: Robyn L. Ward, Sian Hicks, Nicholas J. Hawkins
Journal: Journal of Clinical Oncology (2013)

Molecular screening techniques are available to identify hereditary Lynch syndrome in people with newly diagnosed colorectal cancer (CRC). We aimed to determine whether decisions of patients or clinicians reduced detection of Lynch syndrome.A prospective cohort of 245 consecutive individuals with mismatch repair-deficient CRC recruited from a population-based molecular screening program of all incident patient cases of CRC in a health care region of 1.2 million inhabitants. All incident CRCs were analyzed for mismatch repair protein loss, supported by BRAF mutation and microsatellite instability testing. Advice regarding referral for germline testing was provided to treating surgeons.The mean age of patients was 72.5 ± standard deviation of 12 years; 64% were women; 65% had BRAF-mutant cancers. Consent for germline testing was received from 194 patients (79%): 120 with low and 74 with high likelihood of Lynch syndrome based on tumor molecular profile. Of patients who consented, 143 provided samples for germline analysis, with 12 of 143 showing a mutation (8.4%; 95% CI, 4.4% to 14.2%). Among the 102 patients who chose not to provide a sample or did not consent, an estimated 5.3 of 102 had germline mutations (5.2%; 95% CI, 2.0% to 17.5%).A universal screening strategy for Lynch syndrome is potentially effective because the overall estimate of germline mutations was 17.3 of 245 patient cases (7.1%; 95% CI, 2.8% to 18.2%). However, the true value of screening is likely to be greatly limited by the decisions and circumstances of patients in taking up germline testing.
Rise in children on adult mental health wards is condemned by UK doctors and campaigners
Authors: J. Wise
Journal: BMJ (2014)

Official figures have confirmed a rise in the number of children and adolescents with mental health problems who are treated in adult wards in England. The issue was recently highlighted in the media through freedom of information requests from mental health trusts.

Data from the Health and Social Care Information Centre showed that more under 18s were treated in adult mental health wards in the first eight months of 2013-14 than in the whole of the previous year, reversing an earlier trend of falling numbers of children on adult wards.

Sue Bailey, president of the Royal College of Psychiatrists, said that the latest figures were very worrying. “It is completely unacceptable that under 18s are being treated on adult psychiatric wards, and it can be a frightening and distressing experience for young …
GENETIC VARIANTS IN SOX5 AND CAV1 ARE ASSOCIATED WITH ABNORMAL ATRIAL ACTIVATION IN PATIENTS WITH LONE ATRIAL FIBRILLATION
Authors: Mariam Bashir Seifert, Morten S. Olesen, Ingrid E. Christophersen, Jonas B. Nielsen, Jonas Carlson, Arnljot Tveit, Jesper H. Svendsen, Pyotr G. Platonov
Journal: Journal of the American College of Cardiology (2014)
Does optimal or stent-like PTCA provide equivalent outcomes compared to primary stenting in acute myocardial infarction? Early and late results from the CADILLAC trial
Authors: David A. Cox, Cindy Grines, Eulogio Garcia, Thomas Stuckey, James Tcheng, Giulio Guagliumi, Adeyemi Johnson, Alexandra Lansky, John Griffin, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2002)
Renal Hypertension
Authors: Walter M. Kirkendall, Annette E. Fitz, Montague S. Lawrence
Journal: New England Journal of Medicine (1967)

EXPERIMENTAL evidence in animals and clinical experience in man show that hypertension may result from renal vascular and parenchymal lesions. Surgery to remove the diseased kidney or to repair the vascular defect often relieves such hypertension. Many tests have been suggested to detect patients who might benefit from operation, but the role of some of these procedures is not yet established. One purpose of this paper is to present information concerning the value of some widely used tests, as well as examinations of peripheral and renal-vein blood for renin, as tools for predicting operative success. Reports of surgical efforts to . . .
Primary thrombophilia in Mexico: A prospective study
Authors: Guillermo J. Ruiz-Arg�elles, Sonia Gonz�lez-Estrada, Javier Garc�s-Eisele, Alejandro Ruiz-Arg�elles
Journal: American Journal of Hematology (1999)

A group of 102 Mexican Mestizo patients with appropriate clinical features suggestive of primary thrombophilia was prospectively studied. Thirty-nine percent of them had activated protein C resistance, but only four patients displayed the factor V Leiden mutation. Five percent of the individuals were found to be protein C deficient, whereas 2% had protein S deficiency. No cases of abnormalities in antithrombin III, plasminogen, tissue-type plasminogen activator or plasminogen activator inhibitor were found. The low prevalence of the activated protein C resistance genotype, probably stemming from the genetic admixture of the Mexican Mestizo group is noteworthy. Am. J. Hematol. 60:1–5, 1999. © 1999 Wiley-Liss, Inc.
Are Research Ethics Bad for Our Mental Health?
Authors: R Michels
Journal: New England Journal of Medicine (1999)

Patients with mental illness are much better off now than they were only a few decades ago. Diagnostic methods are more reliable, and treatments are more effective. Only a minority of psychiatric patients require long-term hospitalization, and the practice of psychiatry is now more like the practice of other medical specialties. At the same time, the prevalence of psychiatric disease is more clearly recognized. Five of the world's 10 leading causes of disability are psychiatric: depression, alcohol abuse, bipolar mood disorder, schizophrenia, and obsessive–compulsive disorder.1 Each of these disorders has important genetic determinants and biologic correlates. In the past 40 . . .
Radioimmunoguided Surgery Joins Cancer War
Authors: Chris Anne Raymond
Journal: JAMA (1987)

SOME SURGEONS have been known to operate to the soothing strains of Brahms. In the near future, sound—in this case, the whistle of a gamma-ray detector—may emerge from the background to become part of treatment. At an American Cancer Society seminar in San Diego, Edward W. Martin, Jr, MD, presented the results of studies using a probe that detects emissions from radiolabeled antitumor antibody. The sound emitted helps the surgeon to home in on tumor cells. Martin reported that 160 patients with breast, ovarian, upper gastrointestinal, and primary and secondary colorectal cancers were injected with the monoclonal antibody B72.3. After waiting two to three weeks for the antibody to clear areas of high blood flow such as the liver (to eliminate false-positive readings), the surgeons scanned the patients with the hand-held, stainless steel probe. In three fourths of the cases, the probe emitted a sound sufficient to distinguish tumor from
A wicked encyclopaedia
Authors: D. Spence
Journal: BMJ (2009)

I can’t help myself. It’s the hair, the certainty, the complaints about student debt, then the gap year travel tales, and their Facebook avatar: young people irritate me. I go to bed at 10 pm to wake still shattered, but they stay out till 3 am and appear bright (but red) eyed and bushy tailed. The young assume that anyone aged over 30 knows nothing, anyone over 40 is pre-dementing, and those over 50 should be retired. And the young can’t tell middle aged people apart, not even men from women—we all look alike. 

How …
Effect of Adenosine-Regulating Agent Acadesine on Morbidity and Mortality Associated With Coronary Artery Bypass Grafting
Authors: Mark F. Newman, T. Bruce Ferguson, Jennifer A. White, Giuseppe Ambrosio, Joerg Koglin, Nancy A. Nussmeier, Ronald G. Pearl, Bertram Pitt, Andrew S. Wechsler, Richard D. Weisel, Tammy L. Reece, Armando Lira, Robert A. Harrington, for the RED-CABG Steering Committee and Investigators
Journal: JAMA (2012)

Ischemia/reperfusion injury remains an important cause of morbidity and mortality after coronary artery bypass graft (CABG) surgery. In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine, a first-in-class adenosine-regulating agent, was associated with a reduction in early cardiac death, myocardial infarction, and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery.To assess the efficacy and safety of acadesine administered in the perioperative period in reducing all-cause mortality, nonfatal stroke, and severe left ventricular dysfunction (SLVD) through 28 days.The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate- to high-risk patients (median age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. Enrollment occurred from May 6, 2009, to July 30, 2010.Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg per minute for 7 hours) or placebo (both also added to cardioplegic solutions) beginning just before anesthesia induction.Composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD during and following CABG surgery through postoperative day 28.Because results of a prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome, the trial was stopped after 3080 of the originally projected 7500 study participants were randomized. The primary outcome occurred in 75 of 1493 participants (5.0%) in the placebo group and 76 of 1493 (5.1%) in the acadesine group (odds ratio, 1.01 [95% CI, 0.73-1.41]). There were no differences in key secondary end points measured.In this population of intermediate- to high-risk patients undergoing CABG surgery, acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD.clinicaltrials.gov Identifier: NCT00872001.
Small pancreatic lesions: Is there need for EUS-FNA preoperatively? What to do with the incidental lesions?
Authors: H. Maguchi, K. Takahashi, M. Osanai, A. Katanuma
Journal: Endoscopy (2006)

The advantage of endoscopic ultrasonography (EUS) is its high resolution and capability of local observation [1] [2]. It is one of the most accurate diagnostic methods, particularly for the pancreatobiliary region, where various advanced imaging diagnostic methods available today, such as CT and MRI [3] [4]. Since EUS is most useful for diagnosing a small lesion, its usage for early diagnosis of pancreatobiliary cancer has being anticipated.
Esophageal strictures in adult eosinophilic esophagitis: dilation is an effective and safe alternative after failure of topical corticosteroids
Authors: A. Schoepfer, J. Gschossmann, U. Scheurer, F. Seibold, A. Straumann
Journal: Endoscopy (2008)

Strictures are a frequent complication of eosinophilic esophagitis. The efficacy and safety of topical corticosteroids and of dilation of eosinophilic esophagitis-associated strictures have not yet been thoroughly clarified. We present a retrospective analysis of 10 adult patients with eosinophilic esophagitis who had symptomatic esophageal stenosis that was unresponsive to topical corticosteroids, and who were treated using bougienage. Eight patients had one single stricture, one patient had two, and another had three strictures; mean stricture length was 2.1 cm (range 1 - 6 cm). Bougienage led to prompt symptom relief. Apart from transient postprocedural odynophagia, no severe complications occurred. During the follow-up (mean 6 months; range 2 - 11 months), all patients enjoyed sustained treatment response.
The Action of Furmethide (Furfuryl-Trimethy-Lammonium Iodide) on the Bladder in Patients with Urinary Retention Following Surgery on the Rectum
Authors: Joseph H. Lipton, Samuel B. Beaser, Mark D. Altschule
Journal: New England Journal of Medicine (1942)

Original Article from The New England Journal of Medicine — The Action of Furmethide (Furfuryl-Trimethy-Lammonium Iodide) on the Bladder in Patients with Urinary Retention Following Surgery on the Rectum — Preliminary Report