tbuckley/cabot-search huggingface dataset:
Interleukin (IL)-15Rα–deficient Natural Killer Cells Survive in Normal but Not IL-15Rα–deficient Mice
Authors: Rima Koka, Patrick R. Burkett, Marcia Chien, Sophia Chai, Faye Chan, James P. Lodolce, David L. Boone, Averil Ma
Journal: The Journal of Experimental Medicine (2003)

Natural killer (NK) cells protect hosts against viral pathogens and transformed cells. IL-15 is thought to play a critical role in NK cell development, but its role in the regulation of peripheral NK cells is less well defined. We now find that adoptive transfer of normal NK cells into mice lacking the high affinity interleukin (IL)-15 receptor, IL-15Rα, surprisingly results in the abrupt loss of these cells. Moreover, IL-15Rα–deficient NK cells can differentiate successfully in radiation bone marrow chimera bearing normal cells. Finally, adoptively transferred IL-15Rα–deficient NK cells survive in normal but not IL-15Rα–deficient mice. These findings demonstrate that NK cell–independent IL-15Rα expression is critical for maintaining peripheral NK cells, while IL-15Rα expression on NK cells is not required for this function.
Bone remodelling in inflammatory arthritis
Authors: Steven R Goldring, P Edward Purdue, Tania N Crotti, Zhenxin Shen, Merrilee R Flannery, Nikolaus B Binder, F Patrick Ross, Kevin P McHugh
Journal: Annals of the Rheumatic Diseases (2012)

The inflammatory arthropathies that include rheumatoid arthritis, the seronegative spondyloarthropathies and systemic lupus erythematosus are characterised by marked alterations in the architecture and structural integrity of peri-articular bone; however, the pattern and natural history of the skeletal changes differs in these conditions. In part, this can be attributed to differences in the primary anatomical site of the inflammation, but also there is evidence that there are differences in the biological properties and products produced by inflammatory tissues. This review will focus on recent advances in the understanding of the cellular and molecular mechanisms that contribute to the differential pattern of articular bone remodelling in these prototypical inflammatory forms of arthritis.
A New Luminex-Based Peptide Assay to Identify Different Degrees of Milk Allergic Reactivity
Authors: Cansin Sackesen, Jing Lin, Stephanie Schmidt, Robert C. Getts, Jim Kadushin, Gustavo Gimenez, Ebru Arik Yilmaz, Ozlem Cavkaytar, Ozge Soyer, Galina Grishina, Ludmilla Bardina, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2015)
Differential Effect of Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Diabetes Management
Authors: Sadanori Okada, Takeshi Morimoto, Hisao Ogawa, Masao Kanauchi, Masafumi Nakayama, Shiro Uemura, Naofumi Doi, Hideaki Jinnouchi, Masako Waki, Hirofumi Soejima, Mio Sakuma, Yoshihiko Saito
Journal: Diabetes Care (2011)

Recent reports showed that low-dose aspirin was ineffective in the primary prevention of cardiovascular events in diabetic patients overall. We hypothesized that low-dose aspirin would be beneficial in patients receiving insulin therapy, as a high-risk group.This study is a subanalysis of the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial-a randomized, controlled, open-label trial. We randomly assigned 2,539 patients with type 2 diabetes and no previous cardiovascular disease to the low-dose aspirin group (81 or 100 mg daily) or to the no-aspirin group. The median follow-up period was 4.4 years. We investigated the effect of low-dose aspirin on preventing atherosclerotic events in groups receiving different diabetes management.At baseline, 326 patients were treated with insulin, 1,750 with oral hypoglycemic agents (OHAs), and 463 with diet alone. The insulin group had the longest history of diabetes, the worst glycemic control, and the highest prevalence of diabetic microangiopathies. The diet-alone group had the opposite characteristics. The incidence of atherosclerotic events was 26.6, 14.6, and 10.4 cases per 1,000 person-years in the insulin, OHA, and diet-alone groups, respectively. In the insulin and OHA groups, low-dose aspirin did not affect atherosclerotic events (insulin: hazard ratio [HR] 1.19 [95% CI 0.60-2.40]; OHA: HR 0.84 [0.57-1.24]). In the diet-alone group, low-dose aspirin significantly reduced atherosclerotic events, despite the lowest event rates (HR 0.21 [0.05-0.64]).Low-dose aspirin reduced atherosclerotic events predominantly in the diet-alone group and not in the insulin or OHA groups.
Proto-Oncogenes and Human Cancers
Authors: Dennis J. Slamon
Journal: New England Journal of Medicine (1987)

The idea that specific genes or groups of genes are responsible for the induction or maintenance of cancer is by no means new. Recent research efforts to understand such genetic sequences have focused on the study of cellular oncogenes or proto-oncogenes. Much of what we have learned about proto-oncogenes has its basis in studies of the rapidly transforming retroviruses. These viruses are known to cause cancer in a variety of vertebrate species, including primates.The molecular characterization of the genome of the rapidly transforming retroviruses first led to the identification of oncogenic sequences. All of the rapidly transforming retroviruses carry . . .
Effect of oral clodronate on metastatic bone pain: a double-blind, placebo-controlled study.
Authors: A G Robertson, N S Reed, S H Ralston
Journal: Journal of Clinical Oncology (1995)

PURPOSE To study the effects of oral clodronate on bone pain in patients with advanced metastatic bone disease. PATIENTS AND METHODS Fifty-five patients with progressing bone metastases were randomized to receive oral clodronate 1,600 mg/d (n = 27) or matching placebo (n = 28). The main outcome measures were bone pain (visual analog score), analgesic use, and compliance with therapy. RESULTS Visual analog pain score (median [interquartile range]) decreased from the pretreatment value in the clodronate group (-0.9 [-2.6 to -0.4]), but increased in the placebo group (+0.4 [-1.0 to +4.0]) (P = .03 between groups). Analgesic use increased with disease progression to a similar extent in both groups (59% increased use in the clodronate group v 64% of placebo group; difference not significant). Ten patients (37%) in the clodronate group and 12 (46%) in the placebo group withdrew from the study prematurely, most often because of difficulty with swallowing the capsules. CONCLUSION Clodronate improved control of bone pain to a modest degree in patients with advanced metastatic cancer, but did not reduce analgesic requirement significantly. Perhaps as a result of these factors, it proved difficult to maintain patients on therapy. Further studies will be needed to define the role of bisphosphonates such as clodronate in this situation, in comparison with established treatments such as radiotherapy and analgesics.
A multicentre, randomized, double-blind, controlled study of long-term treatment with 0.1% tacrolimus ointment in adults with moderate to severe atopic dermatitis
Authors: S. Reitamo, J.P. Ortonne, C. Sand, F. Cambazard, T. Bieber, R. Folster-Holst, G. Vena, J.D. Bos, P. Fabbri, C. Groenhoej Larsen
Journal: British Journal of Dermatology (2005)

Background Atopic dermatis (AD) is a chronic disease that often requires long‐term treatment. Topical corticosteroids are the usual therapy for patients with AD, but prolonged usage can result in skin atrophy and other side‐effects. Objectives In a randomized, double‐blind, comparative study, to compare the efficacy and safety of a 6‐month treatment period with 0·1% tacrolimus ointment vs. a corticosteroid ointment regimen in adults with moderate to severe AD. Methods Treatment was applied twice daily for a maximum of 6 months. Patients in the tacrolimus treatment group (n = 487) applied 0·1% tacrolimus ointment to all affected areas over the whole body. The patients treated with the corticosteroid regimen (n = 485) applied 0·1% hydrocortisone butyrate ointment to affected areas on the trunk and extremities and 1% hydrocortisone acetate ointment to affected areas on the face and neck. The study primary endpoint was the response rate, i.e. the proportion of patients with at least 60% improvement in the modified Eczema Area and Severity Index (mEASI) between baseline and month 3. Results By month 3, more patients in the 0·1% tacrolimus group responded to treatment (72·6% vs. 52·3% in the corticosteroid group, P < 0·001). The patients treated with 0·1% tacrolimus also showed greater improvement in mEASI, EASI, affected body surface area and physician and patient assessments of global response. Patients applying 0·1% tacrolimus ointment experienced more skin burning (52·4% vs. 13·8% in the corticosteroid group; P < 0·001). In most patients, skin burning was mild to moderate in severity and decreased rapidly after the first week of treatment. There was no increase in the incidence of infections or malignancies over time in either treatment group. Conclusions Long‐term treatment with 0·1% tacrolimus ointment is significantly more efficacious than a corticosteroid ointment regimen in adults with moderate to severe AD.
Potential Value of Regionalized Intensive Care for Mechanically Ventilated Medical Patients
Authors: Jeremy M. Kahn, Walter T. Linde-Zwirble, Hannah Wunsch, Amber E. Barnato, Theodore J. Iwashyna, Mark S. Roberts, Judith R. Lave, Derek C. Angus
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Regionalization has been proposed as a method to improve outcomes for medical patients receiving mechanical ventilation in the intensive care unit.Objectives: To determine the number of patients who would be affected by regionalization and the potential mortality reduction under a regionalized system of care.Methods: We performed a retrospective cohort study with Monte Carlo simulation, using 2001 state discharge data from eight states representing 42% of the U.S. population. Adult medical patients undergoing invasive mechanical ventilation were identified. Patient location and hospital mortality rates were obtained from the discharge data; estimates of the relative risk reduction in hospital mortality for high-volume hospitals compared with low-volume hospitals were obtained from the published literature and applied to the cohort.Measurements and Main Results: Of 180,976 adult medical patients who underwent mechanical ventilation at 1,170 nonfederal hospitals, 83,050 (46%) received mechanical ventilation at 887 (76%) hospitals with low annual volumes (fewer than 275 patients per year). Using published risk estimates, approximately 4,720 lives per year (95% range, 2,522–6,744) could potentially be saved in the 8 states by routinely transferring patients from low- to high-volume hospitals, representing a number needed to treat of 15.7. The median distance that patients would need to travel to reach a high-volume hospital was 8.5 miles (interquartile range, 4.0–21.2 mi).Conclusions: Regionalization of intensive care could potentially improve survival for patients undergoing mechanical ventilation. Transfer distances are modest for most patients.
Diagnosing relapse in children's brain tumors using metabolite profiles
Authors: S. K. Gill, M. Wilson, N. P. Davies, L. MacPherson, M. English, T. N. Arvanitis, A. C. Peet
Journal: Neuro-Oncology (2013)

Malignant brain tumors in children generally have a very poor prognosis when they relapse and improvements are required in their management. It can be difficult to accurately diagnose abnormalities detected during tumor surveillance, and new techniques are required to aid this process. This study investigates how metabolite profiles measured noninvasively by 1H magnetic resonance spectroscopy (MRS) at relapse reflect those at diagnosis and may be used in this monitoring process. Single-voxel MRS (1.5 T, point-resolved spectroscopy, echo time 30 ms, repetition time 1500 ms was performed on 19 children with grades II–IV brain tumors during routine MRI scans prior to treatment for a suspected brain tumor and at suspected first relapse. MRS was analyzed using TARQUIN software to provide metabolite concentrations. Paired Student's t-tests were performed between metabolite profiles at diagnosis and at first relapse. There was no significant difference (P > .05) in the level of any metabolite, lipid, or macromolecule from tumors prior to treatment and at first relapse. This was true for the whole group (n = 19), those with a local relapse (n = 12), and those with a distant relapse (n = 7). Lipids at 1.3 ppm were close to significance when comparing the level at diagnosis with that at distant first relapse (P = .07, 6.5 vs 12.9). In 5 cases the MRS indicative of tumor preceded a formal diagnosis of relapse. Tumor metabolite profiles, measured by MRS, do not change greatly from diagnosis to first relapse, and this can aid the confirmation of the presence of tumor.
Evolution of an X-Linked Primate-Specific Micro RNA Cluster
Authors: J. Li, Y. Liu, D. Dong, Z. Zhang
Journal: Molecular Biology and Evolution (2009)

Micro RNAs (miRNAs) are a class of small regulatory RNAs, which posttranscriptionally repress protein production of the targeted messenger RNAs (mRNAs). Accumulating evidence has suggested lineage-specific miRNAs have contributed to lineage-specific characteristics. However, the birth and death of these miRNAs, particularly in primates, largely remain unexplored. We herein characterized the evolutionary history of a newly discovered miRNA cluster on primate X-chromosome, spanning a ∼33-kb region in human Xq27.3. The cluster consists of six distinct miRNAs, four of which are compactly organized in a 3-kb region belonging to a phylogenetic group distinct from the other two miRNAs. By comparing the genomic structure of this cluster in human with four other primates (chimpanzee, orangutan, rhesus macaque, and marmoset), we identified several previously uncovered miRNAs in these primates that share orthology with the human miRNAs. We found the entire miRNA cluster was well conserved among primate species but unidentifiable in other mammalian species (including mouse, rat, cat, dog, horse, cow, opossum, and platypus), suggesting that the formation of this cluster was after the primate–rodent split but before the emergence of New-World Monkey (represented by marmoset). Our analysis further revealed complex evolutionary dynamics on this locus, characterized by extensive duplication events. Phylogenetic analysis revealed birth and death of the miRNAs within this region, accompanied by rapid evolution, which highlighted their functional importance. These miRNAs are primarily expressed in primate epididymis, part of the male reproductive system. Our analysis showed that their predicted target mRNAs are significantly enriched for several functional classes relevant to epididymal physiology, such as morphogenesis of epithelium and tube development. Furthermore, several genes controlling sperm maturation and male fertility are confidently predicted to be their targets. Collectively, we argue these miRNAs might play an important role in epididymal morphogenesis and sperm maturation and in establishing primate-specific epididymal characteristics.
STUDIES OF INFLUENZA VIRUS INFECTION IN THE CHICK EMBRYO USING FLUORESCENT ANTIBODY
Authors: Barbara K. Watson, Albert H. Coons
Journal: The Journal of Experimental Medicine (1954)

As evidenced by specific staining with fluorescent antibody, the major sites of multiplication of the PR8 and Lee B strains of influenza virus in chick embryos injected by the amniotic route were in the cells lining the amnion and in the epidermal and pharyngeal epithelium. Varying amounts of virus were also present in the epithelium of the allantois and less frequently in the peritoneum. No virus was detectable in any of the other tissues of 25 embryos injected between the 7th and 11th days of incubation and examined 48 hours later. Three out of five of the embryos inoculated with the PR8 strain of influenza virus on the 12th day of incubation, on the other hand, showed in addition extensive involvement of the cells lining the respiratory tract. Specific staining of the tissues was first detectable when the ID(50) of the amniotic fluids attained a level of greater than 4.5, which corresponded to the time of the appearance of hemagglutinins. With the inocula used this was generally achieved sometime between the 18th and 24th hour of the infection with the PR8 strain of virus and between the 24th and 48th hour of the infection with the Lee B strain of virus. Cytologically, the multiplication of the influenza viruses was characterized by a diffuse type of immunospecific staining which was first detectable in the nuclei and later in the cytoplasm of the cells. The infection progressed rapidly and despite the restricted distribution of the viruses resulted in the death of the embryo in from 3 to 6 days. The results obtained in the present experiments are compared with the findings previously reported in similar studies of mumps virus (6).
The influence of sex, allergic rhinitis, and test system on nasal sensitivity to airborne irritants: a pilot study.
Authors: D Shusterman, M A Murphy, J Balmes
Journal: Environmental Health Perspectives (2001)

"Nasal irritant sensitivity" is an important construct in environmental health science; functional measures, however, lack standardization. We performed duplicate measures of nasal irritant perceptual acuity on 16 subjects (evenly divided by sex and seasonal allergy status) using two different test compounds: carbon dioxide (CO2) (detection) and n-propanol (localization). The a priori hypotheses included a) allergic rhinitics will display lower perceptual thresholds than nonrhinitics; b) females will display lower perceptual thresholds than males; and c) estimates of perceptual acuity using the two test systems will be positively correlated. We obtained CO2 detection thresholds using an ascending concentration series, presenting 3-sec pulses of CO2, paired with air in random order, by nasal cannula. We obtained localization thresholds by simultaneously presenting stimuli (ascending concentrations of n-propanol vapor in air) and blanks (saturated water vapor in air) to opposite nostrils, with laterality randomized. In terms of test-retest reliability, individual replicate measures for CO2 detection thresholds correlated more closely than did the localization thresholds of volatile organic compounds (VOC) (r = 0.65 and r = 0.60, respectively). As an intertest comparison, log-transformed individual mean CO2 and VOC measures were positively correlated with an r of 0.63 (p &lt; 0.01). In univariate analyses, sex predicted both log-transformed CO2 and VOC thresholds (females being more "sensitive"; p &lt; 0.05 and 0.001, respectively). Nasal allergies predicted sensory testing results only in the multivariate analysis, and then only for VOC localization (p &lt; 0.05). The question of population variation in nasal irritant sensitivity (as well as the generalizability of results across test compounds) deserves further attention.
28m bill for compromise agreements that left staff feeling "gagged," says UK watchdog
Authors: A. O'Dowd
Journal: BMJ (2013)

The United Kingdom’s public spending watchdog, the National Audit Office, has raised concerns about the inconsistent nature and lack of transparency and accountability in the use of compromise agreements in the public sector, in a report published on 21 June.1

The report estimated that £28.4m (€33.3m; $43.6m) has been paid out in the three years up to March 2013, in so called special severance payments to employees collectively signing 1053 compromise agreements with their former employer.

Public sector workers can be offered these payments in return for terminating their employment contract and agreeing to keep the facts surrounding the payment confidential. 

The office investigated the practice by obtaining …
Lack of Interaction of Buprenorphine With Flunitrazepam Metabolism
Authors: Tansel Kilicarslan, Edward M. Sellers
Journal: American Journal of Psychiatry (2000)

The authors' goal was to determine if the reported clinical adverse interaction of flunitrazepam and buprenorphine was caused by inhibition of drug metabolism.Inhibition of flunitrazepam metabolism by buprenorphine and norbuprenorphine were determined in three human liver microsome preparations carrying the CYP2C19*1/*1 allele. Omeprazole metabolism mediated by CYP2C19 and CYP3A4 was used as a control reaction. Apparent K(i) values were determined.Norbuprenorphine did not inhibit the metabolism of flunitrazepam or omeprazole. Buprenorphine inhibited the formation of CYP3A4-mediated pathways of 3-hydroxyflunitrazepam and omeprazole sulfone formation (K(i) 118 and 16 microM) in human liver microsomes. Corresponding values were 38 and 90 microM in cDNA-expressed CYP3A4 microsomes. Projected in vivo inhibition of CYP3A4-mediated metabolism of flunitrazepam by buprenorphine is 0. 1%-2.5%. Estimated inhibition of buprenorphine N-dealkylation by flunitrazepam in vivo is 0.08%.The clinical interaction of flunitrazepam and buprenorphine is likely based on a pharmacodynamic mechanism.
Tear Me Down
Authors: Cam Patterson, Andrea L. Portbury, Jonathan C. Schisler, Monte S. Willis
Journal: Circulation Research (2011)

Cardiac hypertrophy develops most commonly in response to hypertension and is an independent risk factor for the development of heart failure. The mechanisms by which cardiac hypertrophy may be reversed to reduce this risk have not been fully determined to the point where mechanism-specific therapies have been developed. Recently, proteases in the calpain family have been implicated in the regulation of the development of cardiac hypertrophy in preclinical animal models. In this review, we summarize the molecular mechanisms by which calpain inhibition has been shown to modulate the development of cardiac (specifically ventricular) hypertrophy. The context within which calpain inhibition might be developed for therapeutic intervention of cardiac hypertrophy is then discussed.