tbuckley/cabot-search huggingface dataset:
Resident Pleural Macrophages Are Key Orchestrators of Neutrophil Recruitment in Pleural Inflammation
Authors: Jean François Cailhier, Deborah A. Sawatzky, Tiina Kipari, Kris Houlberg, Dave Walbaum, Simon Watson, Richard A. Lang, Spike Clay, David Kluth, John Savill, Jeremy Hughes
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: The role played by resident pleural macrophages in the initiation of pleural inflammation is currently unclear.Objective: To evaluate the role of resident pleural macrophages in the initiation of inflammation.Methods: We have used a conditional macrophage ablation strategy to determine the role of resident pleural macrophages in the regulation of neutrophil recruitment in a murine model of experimental pleurisy induced by the administration of carrageenan and formalin- fixed Staphylococcus aureus.Measurements and Main Results: Conditional macrophage ablation mice express the human diphtheria toxin receptor under the control of the CD11b promoter such that the administration of diphtheria toxin induces ablation of nearly 97% of resident macrophages. Ablation of resident pleural macrophages before the administration of carrageenan or S. aureus dramatically reduced neutrophil influx into the pleural cavity. In the carrageenan model, the reduction in neutrophil infiltration was associated with marked early reduction in the level of macrophage inflammatory protein 2 as well as reduced levels of various cytokines, including tumor necrosis factor α, interleukin 6, and interleukin 10. Adoptive transfer of nontransgenic macrophages partially restored neutrophil infiltration. We also stimulated macrophage-depleted and nondepleted pleural cell populations with carrageenan in vitro and determined the production of chemokines and cytokines. Chemokine and cytokine production was markedly reduced by macrophage depletion, reinforcing the role of resident pleural macrophages in the generation of mediators that initiate acute inflammation.Conclusion: These studies indicate a critical role for resident pleural macrophages in sensing perturbation to the local microenvironment and orchestrating subsequent neutrophil infiltration.
Non-steroidal anti-inflammatory drug use does not appear to be associated with increased cardiovascular mortality in patients with inflammatory polyarthritis: results from a primary care based inception cohort of patients
Authors: N J Goodson, A M Brookhart, D P M Symmons, A J Silman, D H Solomon
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: There is controversy about the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular disease (CVD) mortality. The aim of this study was to explore associations between NSAID use and mortality in patients with inflammatory polyarthritis (IP). Subjects and methods: A total of 923 patients with new onset (IP), recruited to the UK Norfolk Arthritis Register (NOAR) between 1990–1994, were followed up to the end of 2004. Current medication was recorded annually for the first 6 years and then every 2–3 years. Rheumatoid factor (RF) and C-reactive protein (CRP) were measured. Logistic regression was used to calculate all cause and CVD mortality odds ratios (OR) for NSAID use at baseline and during follow-up, adjusting for gender and time-varying covariates: RF, CRP, joint counts, smoking, steroid use, DMARD use and other medication use. Results: By 2004 there were 203 deaths, 85 due to CVD. At baseline, NSAIDs were used by 66% of patients. In final multivariate models, baseline NSAID use was inversely associated with all cause mortality (adjusted OR 0.62, 95% CI 0.45 to 0.84) and CVD mortality (adjusted OR 0.54, 95% CI 0.34 to 0.86). Interval NSAID use had weaker mortality associations: all cause mortality (adjusted OR 0.72, 95% CI 0.52 to 1.00), CVD mortality (adjusted hazard ratio (HR) 0.66, 95% CI 0.40 to 1.08). Conclusion: No excess CVD or all cause mortality was observed in NSAID users in this cohort of patients with IP. This is at variance with the literature relating to NSAID use in the general population. It is unclear whether this represents unmeasured confounders influencing a doctor’s decision to avoid NSAIDs in the treatment of IP.
Protective effect of loop diuretics, piretanide and frusemide, against sodium metabisulphite-induced bronchoconstriction in asthma
Authors: CT Yeo, BJ O'Connor, M Chen-Worsdell, PJ Barnes, KF Chung
Journal: European Respiratory Journal (1992)

We determined whether the loop diuretic, piretanide, had a similar inhibitory action against sodium metabisulphite (MBS)-induced bronchoconstriction in asthmatic subjects as frusemide and, if so, its duration of action. In the first study, we compared the effect of inhaled placebo, piretanide (24 mg), or frusemide (40 mg), on the provocative concentration of MBS needed to cause a 20% fall in baseline forced expiratory volume in one second (FEV1) (PC20MBS) in 12 mild asthmatic subjects before, immediately after, and at 1.5, 3, 6, and 24 h, after inhalation. Both piretanide and frusemide induced a significant diuresis lasting at least 24 h. Frusemide caused a mean 3.8 fold (95% confidence interval: 2.3-6.3 fold), piretanide a 2.5 fold (1.8-3.4 fold) and placebo a 1.7 fold (1.5-1.9 fold) increase in PC20MBS. The effects of frusemide and piretanide were significantly greater than that of placebo. At later time points, tachyphylaxis to the bronchoconstrictor effects of MBS was observed during the placebo limb. In the second study, we measured PC20MBS at 90 min after inhalation of either placebo, piretanide (24 mg), or frusemide (40 mg). No significant difference in PC20MBS was observed. We conclude that piretanide in addition to frusemide significantly inhibits MBS-induced bronchoconstriction and that this action is short-lived over less than 90 min. Frusemide was more potent in inhibiting MBS-induced bronchoconstriction despite causing a smaller diuretic effect than piretanide. The basic mechanism of action of the loop diuretics in the airways remains unclear.
Sensitivity and specificity of bispectral index for classification of overt hepatic encephalopathy: a multicentre, observer blinded, validation study
Authors: A A Dahaba, H C Worm, S M Zhu, F P Bao, A Salah, S Zakaria, H Bornemann, V Stadlbauer, P H Rehak, H Metzler, R E Stauber
Journal: Gut (2007)

<h3>Background:</h3> The severity of hepatic encephalopathy is currently graded clinically using West Haven criteria and psychometric tests. <h3>Objective:</h3> To assess the discriminative power of the bispectral index (BIS) monitor to classify the degree and progression of hepatic encephalopathy. <h3>Design:</h3> A consecutive, multicentre, observer blinded validation study. <h3>Setting:</h3> Medical University of Graz (Graz, Austria), Zhejiang University First Affiliated Hospital (Hang Zhou, China), and Cairo University (Cairo, Egypt). <h3>Patients:</h3> 28 consecutive patients with hepatic encephalopathy were first enrolled at Medical University of Graz as a test set. The estimated BIS cut off values were subsequently tested in a validation set of 31 patients at Zhejiang University First Affiliated Hospital and 26 patients at Cairo University; 18 patients were reassessed later in a longitudinal study. Fifteen of 85 patients (18%) were excluded from the final analysis (11 became too agitated with high electromyographic activity; four fell asleep during the recording). <h3>Results:</h3> Applying the Austrian BIS cut off values of 85, 70, and 55 for discriminating West Haven grades 1 to 4 yielded agreement between BIS classification and West Haven grades in 40 of the 46 validation patients (87%), and in 16 of the 18 follow up patients (89%). Mean (SD) BIS values differed significantly between patients with West Haven grade 1 (90.2 (2.5)), grade 2 (78.4 (6.6)), grade 3 (63.2 (4.8)), and grade 4 (45.4 (5.0)). <h3>Conclusions:</h3> BIS is a useful measure for grading and monitoring the degree of involvement of the central nervous system in patients with chronic liver disease.
In Memoriam: Jeffrey Gray (1934–2004)
Authors: Helen Hodges, Stevan Harnad, Barbara L. Finlay, Paul Bloom
Journal: Behavioral and Brain Sciences (2004)

Many strands are woven into the ideas and work of Jeffrey Gray. From a background of classical languages and a spell in military intelligence spent honing skills in languages and typing, he took two BA degrees (in modern languages and psychology) at Oxford University. He then trained as a clinical psychologist at the Institute of Psychiatry (IOP), London, capping this with a PhD on the sources of emotional behaviour.
Pathogenetic difference between collagen arthritis and adjuvant arthritis.
Authors: N Kaibara, T Hotokebuchi, K Takagishi, I Katsuki, M Morinaga, C Arita, S Jingushi
Journal: The Journal of Experimental Medicine (1984)

Daily treatment with cyclosporin at a dose of 25 mg/kg for 14 d gave complete suppression of the development of collagen arthritis and adjuvant arthritis in Sprague-Dawley rats during an observation period of 45 d. To study whether the immunologic unresponsiveness produced by cyclosporin is antigen specific, we rechallenged the cyclosporin-protected rats with either type II collagen or complete Freund's adjuvant (CFA) after discontinuation of cyclosporin treatment. Type II collagen-immunized, cyclosporin-protected rats did not develop arthritis in response to reimmunization with type II collagen, but, they did develop arthritis in response to a subsequent injection of CFA. Similarly, CFA-injected, cyclosporin-protected rats showed a suppressed arthritogenic reaction in response to reinjection of CFA, whereas their response to a subsequent immunization with type II collagen was unaffected. On the other hand, the rats that were treated with cyclosporin without any prior antigenic challenge could develop arthritis in response to a subsequent injection of CFA or type II collagen after cessation of cyclosporin treatment. These results indicate that specific immunologic unresponsiveness can be induced by cyclosporin in the two experimental models of polyarthritis, collagen arthritis and adjuvant arthritis, and that there is no cross-reactivity between type II collagen and the mycobacterial cell wall components. The results further indicate that immunity to type II collagen plays a critical role in the pathogenesis of collagen arthritis but that its pathogenetic role in adjuvant arthritis is insignificant.
The genome of woodland strawberry (Fragaria vesca)
Authors: Vladimir Shulaev, Daniel J Sargent, Ross N Crowhurst, Todd C Mockler, Otto Folkerts, Arthur L Delcher, Pankaj Jaiswal, Keithanne Mockaitis, Aaron Liston, Shrinivasrao P Mane, Paul Burns, Thomas M Davis, Janet P Slovin, Nahla Bassil, Roger P Hellens, Clive Evans, Tim Harkins, Chinnappa Kodira, Brian Desany, Oswald R Crasta, Roderick V Jensen, Andrew C Allan, Todd P Michael, Joao Carlos Setubal, Jean-Marc Celton, D Jasper G Rees, Kelly P Williams, Sarah H Holt, Juan Jairo Ruiz Rojas, Mithu Chatterjee, Bo Liu, Herman Silva, Lee Meisel, Avital Adato, Sergei A Filichkin, Michela Troggio, Roberto Viola, Tia-Lynn Ashman, Hao Wang, Palitha Dharmawardhana, Justin Elser, Rajani Raja, Henry D Priest, Douglas W Bryant, Samuel E Fox, Scott A Givan, Larry J Wilhelm, Sushma Naithani, Alan Christoffels, David Y Salama, Jade Carter, Elena Lopez Girona, Anna Zdepski, Wenqin Wang, Randall A Kerstetter, Wilfried Schwab, Schuyler S Korban, Jahn Davik, Amparo Monfort, Beatrice Denoyes-Rothan, Pere Arus, Ron Mittler, Barry Flinn, Asaph Aharoni, Jeffrey L Bennetzen, Steven L Salzberg, Allan W Dickerman, Riccardo Velasco, Mark Borodovsky, Richard E Veilleux, Kevin M Folta
Journal: Nature Genetics (2010)

The International Strawberry Sequencing Consortium reports the draft genome of the woodland strawberry (Fragaria vesca). The genome of this diploid species should serve as a reference genome for the Fragaria genus, as the cultivated strawberry (Fragaria × ananassa) is an octoploid where F. vesca is predicted to be a subgenome donor. The woodland strawberry, Fragaria vesca (2n = 2x = 14), is a versatile experimental plant system. This diminutive herbaceous perennial has a small genome (240 Mb), is amenable to genetic transformation and shares substantial sequence identity with the cultivated strawberry (Fragaria × ananassa) and other economically important rosaceous plants. Here we report the draft F. vesca genome, which was sequenced to ×39 coverage using second-generation technology, assembled de novo and then anchored to the genetic linkage map into seven pseudochromosomes. This diploid strawberry sequence lacks the large genome duplications seen in other rosids. Gene prediction modeling identified 34,809 genes, with most being supported by transcriptome mapping. Genes critical to valuable horticultural traits including flavor, nutritional value and flowering time were identified. Macrosyntenic relationships between Fragaria and Prunus predict a hypothetical ancestral Rosaceae genome that had nine chromosomes. New phylogenetic analysis of 154 protein-coding genes suggests that assignment of Populus to Malvidae, rather than Fabidae, is warranted.
MYCN oncogene amplification in neuroblastoma is associated with worse prognosis, except in stage 4s: the Italian experience with 295 children.
Authors: G P Tonini, L Boni, A Pession, D Rogers, A Iolascon, G Basso, L Cordero di Montezemolo, F Casale, A Pession, P Perri, K Mazzocco, P Scaruffi, C Lo Cunsolo, N Marchese, C Milanaccio, M Conte, P Bruzzi, B De Bernardi
Journal: Journal of Clinical Oncology (1997)

PURPOSE To evaluate the prognostic role of MYCN oncogene amplification in children with neuroblastoma. PATIENTS AND METHODS Of 694 children (age, 0 to 15 years) with previously untreated neuroblastoma, 295 (42%) were evaluated at diagnosis for MYCN gene amplification. RESULTS Clinical characteristics and survival results of 295 patients studied and 399 not studied for MYCN were comparable. In 48 of 295 patients studied for MYCN (16%), the gene was amplified (&gt; or = three gene copies). Amplification was more frequent in children older than 1 year, with abdominal tumor (18% v 7%), advanced disease, normal vanillylmandelic (VMA) urinary excretion, and high lactate dehydrogenase (LDH), ferritin, and neuron-specific enolase (NSE) serum levels. In patients studied for MYCN, the 5-year overall survival (OS) rate was higher for children aged less than 1 year (90% v 44%), with extraabdominal tumor, stage 1 or 2 versus 3 versus 4, and normal NSE, LDH, and ferritin serum levels. Patients with amplified MYCN had a worse OS (odds ratio [OR], 3.38; confidence interval [CI], 2.22 to 5.16). This association held after adjustment for other characteristics. The impact of MYCN amplification was greater in patients with favorable characteristics, in particular age (OR, 10.28 for infants; 2.08 for older children) and stage (OR, 35.3 for stage 1 to 2; 8.41 for stage 3; 1.76 for stage 4). However, of 29 children with stage 4s, all three with amplified MYCN survive. In a multivariate analysis, the prognostic role of MYCN amplification, age, and stage was confirmed, but the size of the effect of MYCN was dependent on age and stage. CONCLUSION MYCN amplification is associated with a worse prognosis in children with neuroblastoma at all ages and stages except 4s. This association is most pronounced in children with otherwise favorable prognostic indicators, and in these children should be considered as an indication for more intensive intervention.
Peripheral Blood Tyrosinase Messenger RNA Detection and Survival in Malignant Melanoma
Authors: U. Kunter, J. Buer, M. Probst, S. Duensing, I. Dallmann, J. Grosse, H. Kirchner, E. M. Schluepen, M. Volkenandt, A. Ganser, J. Atzpodien
Journal: JNCI Journal of the National Cancer Institute (1996)

The most widely accepted criteria for the evaluation of prognosis of malignant melanoma are histopathologic and clinical presentation. No currently available laboratory tests provide additional prognostic information. It has recently been suggested that reverse transcription and polymerase chain reaction (RT-PCR)-based detection of tyrosinase messenger RNA (mRNA) in peripheral blood might be useful in the early detection of circulating tumor cells, since tyrosinase is thought to be a melanocyte-specific marker.To further evaluate the clinical relevance of this potential marker, we examined peripheral blood samples from patients with malignant melanoma in different stages of disease for the presence of tyrosinase mRNA.Total cellular RNA was extracted from heparinized peripheral blood cells from 64 patients with malignant melanoma, from five healthy control subjects, and from four patients with other cancers using the RNAzol A method. For analysis of tyrosinase mRNA, RT-PCR was performed as previously described by Smith et al.; the sensitivity of this assay was tested using RNA extracted from human melanoma cells (SK-mel 1 and SK-mel 3 cell lines) serially diluted with peripheral blood obtained from healthy control subjects. Two additional human melanoma cell lines (SK-mel 30 and RPMI-7951) served as positive controls for RT-PCR detection of tyrosinase mRNA. Overall patient survival curves were constructed using Kaplan-Meier estimates.Tyrosinase mRNA was detected by RT-PCR assay of all four of the established melanoma cell lines tested. Nine of the 64 patients with malignant melanoma were found to have detectable tyrosinase mRNA in their peripheral blood cells (tyrosinase-positive patients). The 16 patients with localized primary melanoma did not have detectable tyrosinase mRNA in their peripheral blood cells. Among the 48 patients with metastatic disease, all 27 patients who exhibited no evidence of disease progression were tyrosinase negative. Notably, all nine tyrosinase-positive patients had visceral metastases and were found to exhibit disease progression at the time of the sampling. Four of the nine tyrosinase-positive patients were also found to test negative at times without evidence of progressive disease; one patient became negative after achieving stable disease and three became positive for tyrosinase transcripts on disease progression. The probability of survival from time of sampling was significantly lower in the nine tyrosinase-positive patients when tested versus the 23 patients with comparable disease but without detectable tyrosinase mRNA (two-sided; P < or = .05).The results of this study demonstrate that the detection of tyrosinase mRNA in cells in the peripheral blood by RT-PCR may be a useful prognostic marker for predicting tumor progression and poor clinical outcome in patients with malignant melanoma.
Somatically acquired <i>JAK1</i> mutations in adult acute lymphoblastic leukemia
Authors: Elisabetta Flex, Valentina Petrangeli, Lorenzo Stella, Sabina Chiaretti, Tekla Hornakova, Laurent Knoops, Cristina Ariola, Valentina Fodale, Emmanuelle Clappier, Francesca Paoloni, Simone Martinelli, Alessandra Fragale, Massimo Sanchez, Simona Tavolaro, Monica Messina, Giovanni Cazzaniga, Andrea Camera, Giovanni Pizzolo, Assunta Tornesello, Marco Vignetti, Angela Battistini, Hélène Cavé, Bruce D. Gelb, Jean-Christophe Renauld, Andrea Biondi, Stefan N. Constantinescu, Robin Foà, Marco Tartaglia
Journal: The Journal of Experimental Medicine (2008)

Aberrant signal transduction contributes substantially to leukemogenesis. The Janus kinase 1 (JAK1) gene encodes a cytoplasmic tyrosine kinase that noncovalently associates with a variety of cytokine receptors and plays a nonredundant role in lymphoid cell precursor proliferation, survival, and differentiation. We report that somatic mutations in JAK1 occur in individuals with acute lymphoblastic leukemia (ALL). JAK1 mutations were more prevalent among adult subjects with the T cell precursor ALL, where they accounted for 18% of cases, and were associated with advanced age at diagnosis, poor response to therapy, and overall prognosis. All mutations were missense, and some were predicted to destabilize interdomain interactions controlling the activity of the kinase. Three mutations that were studied promoted JAK1 gain of function and conferred interleukin (IL)-3–independent growth in Ba/F3 cells and/or IL-9–independent resistance to dexamethasone-induced apoptosis in T cell lymphoma BW5147 cells. Such effects were associated with variably enhanced activation of multiple downstream signaling pathways. Leukemic cells with mutated JAK1 alleles shared a gene expression signature characterized by transcriptional up-regulation of genes positively controlled by JAK signaling. Our findings implicate dysregulated JAK1 function in ALL, particularly of T cell origin, and point to this kinase as a target for the development of novel antileukemic drugs.
Electrocardiographic Changes in Amitriptyline Poisoning
Authors: R. J. Barnes, S. M. Kong, R. W. Y. Wu
Journal: BMJ (1968)

In imipramine and amitriptyline poisoning the electrocardiographic abnormalities comprise arrhythmias, widening of the QRS complex, and marked changes in die S-T segment. These features were found to be of value in the differential diagnosis of unknown poisoning. The unusual configuration of qR with raised S-T segment in V1, simulating myocardial infarction, was seen in one of our patients and has been noted in four cases reported by other workers.
Long-Term Weight Loss and Prevention of Cardiovascular Disease
Authors: Robert Clarke
Journal: Circulation (2011)

T he prevalence of obesity has increased dramatically over the last few decades, not only in North America, but also in Europe, Latin America, North Africa, and many parts of Asia. 1 Using the World Health Organization definitions for obesity (body mass index [BMI] Ն30 kg/m 2 ) and overweight (BMI, 25.0 -29.9 kg/m 2 ) shows that about 1 in 3 middle-aged adults in the United States is obese and 2 in 3 are overweight or obese. 2 Thus, excess body weight is a global public health problem that is most serious in the United States.
Primary mediastinal trophoblastic teratomas.
Authors: P A Walden, R L Woods, B Fox, K D Bagshawe
Journal: Thorax (1977)

Three cases of primary mediastinal trophoblastic teratoma are described. One patient died from respiratory failure during the initial chemotherapy, Another patient with advanced disease is now apparently free from disease after multiple-drug chemotherapy. The third patient is alive and well four years after a combination of surgery, radiotherapy, and multiple-drug chemotherapy. In the diagnosis and assessment of response to treatment in these tumours emphasis is placed on the measurement of the tumour cell markers, chorionic gonadotrophin and alpha-fetoprotein, by radioimmunoassay. The efficacy of multiple-drug regimens is discussed together with a review of the literature.