tbuckley/cabot-search huggingface dataset:
One caution in pneumatic antishock garment use
Authors: G. McBride
Journal: JAMA (1982)

A set of unusual circumstances surrounding a home birth in California in which the mother ultimately died has caused a forensic pathologist to issue a warning to emergency room physicians and paramedical personnel about the use of the pneumatic anti-shock garment in similar cases. According to Claus Speth, MD, one of the forensic pathologists for the coroner of San Bernardino County, California, the natural home childbirth—a term pregnancy—was attended by an unlicensed midwife and an assistant. The birth was normal but the placenta was not delivered, and hemorrhage began. The midwife and assistant were unable to help, and the husband became worried and started cardiopulmonary resuscitation. Finally he called emergency medical technicians (EMTs), who arrived about an hour after the birth. The woman by then had lost a moderate amount of blood, according to witnesses, and was in shock. All vital signs were present for some time, and during the
Distinct Pathways of Ca <sup>2+</sup> Sensitization in Porcine Coronary Artery
Authors: Koji Nobe, Richard J. Paul
Journal: Circulation Research (2001)

Abstract —Alterations of the Ca 2+ sensitivity of contraction have been reported for porcine coronary artery, but the mechanisms are not clearly understood. We investigated the mechanism(s) of Ca 2+ sensitization in response to the thromboxane A 2 analogue (U46619). Our hypothesis is that different mechanisms of Ca 2+ sensitization could be distinguished by their distinct time courses. Therefore, we measured the time course of [Ca 2+ ] i and isometric force simultaneously in an intact artery after a single addition of U46619. The initial transient phase was associated with Ca 2+ release from the sarcoplasmic reticulum, whereas the maintained phase was associated with Ca 2+ influx. Two distinct types of Ca 2+ sensitization characterized these phases with either protein kinase C (PKC)-mediated or Rho-kinase–mediated mechanisms. Their effects were quite distinct on the basis of the time courses over which the sensitization was effective. PKC inhibition (1 μmol/L calphostin C) had a much greater effect in the initial phase, diminishing the size of the transient and prolonging the rise in force and the decline in [Ca 2+ ] i . There were limited effects on the sustained force. Rho-kinase inhibition (10 μmol/L Y27632), in contrast, nearly abolished the sustained force but had a lesser effect on the transient phase. Neither inhibitor had any effect on the force versus [Ca 2+ ] i relations for KCl contractures. Our evidence suggests that both PKC-mediated and Rho-kinase–mediated Ca 2+ sensitizations are present in coronary arteries, but the latter is dominant in thromboxane A 2 receptor–mediated contraction.
ENERGETICS OF FREE-RANGING MAMMALS, REPTILES, AND BIRDS
Authors: K. A. Nagy, I. A. Girard, T. K. Brown
Journal: Annual Review of Nutrition (1999)

We summarize the recent information on field metabolic rates (FMR) of wild terrestrial vertebrates as determined by the doubly labeled water technique. Allometric (scaling) relationships are calculated for mammals (79 species), reptiles (55 species), and birds (95 species) and for various taxonomic, dietary, and habitat groups within these categories. Exponential equations based on body mass are offered for predicting rates of daily energy expenditure and daily food requirements of free-ranging mammals, reptiles, and birds. Significant scaling differences between various taxa, dietary, and habitat groups (detected by analysis of covariance with P < or = 0.05) include the following: (a) The allometric slope for reptiles (0.889) is greater than that for mammals (0.734), which is greater than that for birds (0.681); (b) the slope for eutherian mammals (0.772) is greater than that for marsupial mammals (0.590); (c) among families of birds, slopes do not differ but elevations (intercepts) do, with passerine and procellariid birds having relatively high FMRs and gallinaceous birds having low FMRs; (d) Scleroglossan lizards have a higher slope (0.949) than do Iguanian lizards (0.793); (e) desert mammals have a higher slope (0.785) than do nondesert mammals; (f) marine birds have relatively high FMRs and desert birds have low FMRs; and (g) carnivorous mammals have a relatively high slope and carnivorous, insectivorous, and nectarivorous birds have relatively higher FMRs than do omnivores and granivores. The difference detected between passerine and nonpasserine birds reported in earlier reviews is not evident in the larger data set analyzed here. When the results are adjusted for phylogenetic effects using independent contrasts analysis, the difference between allometric slopes for marsupials and eutherians is no longer significant and the slope difference between Scleroglossan and Iguanian lizards disappears as well, but other taxonomic differences remain significant. Possible causes of the unexplained variations in FMR that could improve our currently inaccurate FMR prediction capabilities should be evaluated, including many important groups of terrestrial vertebrates that remain under- or unstudied and such factors as reproductive, thermoregulatory, social, and predator-avoidance behavior.
Implication of the folate-methionine metabolism pathways in susceptibility to follicular lymphomas
Authors: Sidonie Niclot, Quentin Pruvot, Caroline Besson, Daniel Savoy, Elisabeth Macintyre, Gilles Salles, Nicole Brousse, Bruno Varet, Paul Landais, Pierre Taupin, Claudine Junien, Dominique Baudry-Bluteau
Journal: Blood (2006)
Clinicopathologic correlations. De subitaneis mortibus. XXV. Sarcoid heart disease.
Authors: T N James
Journal: Circulation (1977)

Postmortem findings within the cardiac conduction system are described from the case of a black woman with sarcoid heart disease who died suddenly. Her clinical course had been characterized by recurring ventricular arrhythmias and bouts of syncope. Both the sinus node artery and the atrioventricular (A-V) node artery were sites of focal fibromuscular dysplasia, which thickened slightly the wall of the former but markedly narrowed the lumen of the latter. Small foci of sarcoid infiltration were present in the sinus node and the A-V node. Fatty replacement within the His bundle was attributable to the probable ischemia caused by narrowing of the A-V node artery. Sarcoid granulomata and infiltration with epithelioid cells were present throughout the ventricular myocardium, but were conspicuously less prevalent in the atria. All the large coronary arteries were normal. Many small coronary arteries in the ventricular myocardium were involved by the sarcoidosis and their lumen were narrowed. These findings and analogous ones reported by others are discussed relative to the pathogenesis of syncopal attacks and sudden death which seem to peculiarly prevalent in sarcoid heart disease.
Microcytic polycythemia. Frequency of nonthalassemic causes
Authors: J. D. Bessman
Journal: JAMA (1977)

A high RBC count combined with a low mean volume generally is attributed to thalassemia minor, either a or β, or to polycythemia vera with iron deficiency. Among 330 patients with a mean corpuscular volume (MCV) less than 70 cuμ, 35 had increased RBC counts. Of these, 26 had thalassemia minor and four had polycythemia vera. Five had secondary polycythemia (four from hypoxia, one from hypernephroma) with incidental iron deficiency. In the four of these patients given iron, the RBC count remained above normal and the MCV rose to normal. The RBC size distribution curves reliably distinguished between thalassemia minor and polycythemia with iron deficiency. (<i>JAMA</i>238:2391-2392, 1977)
Comparison of normal and asthmatic circadian rhythms in peak expiratory flow rate.
Authors: M R Hetzel, T J Clark
Journal: Thorax (1980)

A computer technique (cosinor analysis) has been used to evaluate circadian rhythms in airway calibre in normals and asthmatics. Two hundred and twenty-one normal subjects recorded peak expiratory flow rate (PEFR) at home four times a day for seven days. Rhythm detection was statistically significant in 145 of them (65.6%) who showed a mean amplitude of 8.3% of individual mean PEFR (+/- SD 5.2%). Amplitude was independent of age, sex, atopy, family history of asthma, and smoking habit. Fifteen of them were also studied three times a day for five days in the laboratory with flow-volume loops. Eleven showed significant PEFR rhythms at home. No single measurement from the flow-volume loop showed periodicity in as many of them but rhythms were now also detected in the other four normal subjects in some components of the loop. Fifty-six asthma patients were studied with a similar protocol of PEFR measurement and compared with the 145 rhythmic normal subjects. Mean phases of the normal and asthmatic rhythms were not significantly different with acrophases (peak of rhythm cycle) at 1557 and 1526 respectively. The mean asthmatic amplitude was, however, significantly greater at 50.9%. Nocturnal asthma, therefore, probably represents an exaggeration of a normal circadian rhythm in airway calibre. The amplitude of the PEFR rhythm is an index of bronchial lability and is thus valuable in monitoring asthma patients. An amplitude of greater than 20% should be a useful screening test for asthma.
Correlation of PD-L1 Tumor Expression and Treatment Outcomes in Patients with Renal Cell Carcinoma Receiving Sunitinib or Pazopanib: Results from COMPARZ, a Randomized Controlled Trial
Authors: Toni K. Choueiri, David J. Figueroa, André P. Fay, Sabina Signoretti, Yuan Liu, Robert Gagnon, Keith Deen, Christopher Carpenter, Peter Benson, Thai H. Ho, Lini Pandite, Paul de Souza, Thomas Powles, Robert J. Motzer
Journal: Clinical Cancer Research (2014)

The interaction of programmed death-1 ligand (PD-L1) with its receptor (PD-1) on T cells inactivates antitumor immune responses. PD-L1 expression has been associated with poor outcomes in renal cell carcinoma (RCC) but has not been investigated in advanced RCC patients receiving VEGF-targeted therapy.Formalin-fixed paraffin-embedded specimens were collected at baseline from patients in the COMPARZ trial. Tumor cell PD-L1 expression by IHC was evaluated using H-score (HS). Dual PD-L1/CD68 staining was used to differentiate PD-L1 tumor expression from tumor-associated macrophages. Intratumor CD8-positive T cells were quantified morphometrically. Associations between biomarkers and survival were investigated using the log-rank test.HS data were available from 453 of 1,110 patients. Sixty-four percent of patients had negative PD-L1 expression (HS = 0). Patients with HS > 55 (n = 59, 13%) had significantly shorter overall survival (OS) than those with HS ≤ 55 in both pazopanib and sunitinib arms (median 15.1 vs. 35.6 and 15.3 vs. 27.8 months, respectively, P = 0.03). In both arms, median OS was shortest in patients with HS > 55 and intratumor CD8-positive T-cell counts > 300 (9.6 and 11.9 months with pazopanib and sunitinib, respectively). Median OS in patients with HS ≤ 55 and CD8-positive T-cell counts ≤ 300 was 36.8 and 28.0 months with pazopanib and sunitinib, respectively. Progression-free survival results were similar to OS results.Increased tumor cell PD-L1, or PD-L1 plus tumor CD8-positive T-cell counts, were associated with shorter survival in patients with metastatic RCC receiving VEGF-targeted agents. These findings may have implications for future design of randomized clinical trials in advanced RCC.
Exposure to Diesel Motor Exhaust and Lung Cancer Risk in a Pooled Analysis from Case-Control Studies in Europe and Canada
Authors: Ann C. Olsson, Per Gustavsson, Hans Kromhout, Susan Peters, Roel Vermeulen, Irene Brüske, Beate Pesch, Jack Siemiatycki, Javier Pintos, Thomas Brüning, Adrian Cassidy, Heinz-Erich Wichmann, Dario Consonni, Maria Teresa Landi, Neil Caporaso, Nils Plato, Franco Merletti, Dario Mirabelli, Lorenzo Richiardi, Karl-Heinz Jöckel, Wolfgang Ahrens, Hermann Pohlabeln, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, David Zaridze, Isabelle Stücker, Simone Benhamou, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Peter Rudnai, Eleonora Fabianova, Rodica Stanescu Dumitru, Isabelle M. Gross, Benjamin Kendzia, Francesco Forastiere, Bas Bueno-de-Mesquita, Paul Brennan, Paolo Boffetta, Kurt Straif
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Diesel motor exhaust is classified by the International Agency for Research on Cancer as probably carcinogenic to humans. The epidemiologic evidence is evaluated as limited because most studies lack adequate control for potential confounders and only a few studies have reported on exposure–response relationships.Objectives: Investigate lung cancer risk associated with occupational exposure to diesel motor exhaust, while controlling for potential confounders.Methods: The SYNERGY project pooled information on lifetime work histories and tobacco smoking from 13,304 cases and 16,282 controls from 11 case–control studies conducted in Europe and Canada. A general population job exposure matrix based on ISCO-68 occupational codes, assigning no, low, or high exposure to diesel motor exhaust, was applied to determine level of exposure.Measurements and Main Results: Odds ratios of lung cancer and 95% confidence intervals were estimated by unconditional logistic regression, adjusted for age, sex, study, ever-employment in an occupation with established lung cancer risk, cigarette pack-years, and time-since-quitting smoking. Cumulative diesel exposure was associated with an increased lung cancer risk highest quartile versus unexposed (odds ratio 1.31; 95% confidence interval, 1.19–1.43), and a significant exposure–response relationship (P value < 0.01). Corresponding effect estimates were similar in workers never employed in occupations with established lung cancer risk, and in women and never-smokers, although not statistically significant.Conclusions: Our results show a consistent association between occupational exposure to diesel motor exhaust and increased risk of lung cancer. This association is unlikely explained by bias or confounding, which we addressed by adjusted models and subgroup analyses.
Development of additional autoimmune diseases in a population of patients with primary Sjogren's syndrome
Authors: M N Lazarus
Journal: Annals of the Rheumatic Diseases (2005)

To investigate whether patients with primary Sjögren's syndrome (pSS) have an increased tendency to develop other autoimmune diseases.A retrospective case note review was carried out on 114 patients in whom a diagnosis of pSS had been made in a department of rheumatology from 1979 onwards. The year of diagnosis of pSS was recorded, plus the diagnosis and year of diagnosis of any other identified autoimmune disease.Of the 114 patients with pSS, seven (6%) were male and 107 (94%) female. Mean age at diagnosis of pSS was 53 years (range 21 to 83). Patients were followed up for an average of 10.5 years (range 0 to 23). Thirty eight patients (33.3%) were diagnosed as having another autoimmune disease, while nine (7.9%) had two or more. Thirteen additional autoimmune diseases were identified. Twenty five diagnoses (51.0%) were made before the diagnosis of pSS, three (6.1%) within the same year, and 21 (42.9%) after the diagnosis. Hypothyroidism was the most common autoimmune disease (n = 16).Although pSS is a relatively benign condition, affected individuals have an increased tendency to develop additional autoimmune diseases. Patients with pSS should be monitored on a regular basis for such diseases.
HCV epitope, homologous to multiple human protein sequences, induces a regulatory T cell response in infected patients
Authors: Phyllis T. Losikoff, Sasmita Mishra, Frances Terry, Andres Gutierrez, Matt T. Ardito, Loren Fast, Martha Nevola, William D. Martin, Chris Bailey-Kellogg, Anne S. De Groot, Stephen H. Gregory
Journal: Journal of Hepatology (2014)
"What kills neurons in neurodegenerative diseases?", a review series in an open access journal
Authors: Todd E Golde, Leonard Petrucelli
Journal: Molecular Neurodegeneration (2009)

Over the last several decades there has been great progress with respect to understanding the triggers of most neurodegenerative diseases. For example, genetics studies have identified mutations in superoxide dismutase 1 (SOD1) gene that clearly cause amyotrophic lateral sclerosis. However ask a panel of experts how a mutation in SOD1 causes motor neurons to die and one will receive many different hypothetical answers. There is simply insufficient data to unequivocally support one hypothesis over another. With rare exceptions, this is true for almost all neurodegenerative diseases.

In this review series, we have invited seminal researchers in the field of neurodegeneration to critically review the pathways that potentially lead to neurodegeneration. These reviews include both disease specific reviews (e.g., the role of alpha-synuclein in driving neuronal death in Parkinson's disease) as well as more general reviews that focus on a pathway or a process that could lead to neurodegeneration (e.g., the role of autophagy in neurodegeneration).

As one of us describes in detail in the introductory review The therapeutic importance of understanding mechanisms of neuronal cell death in neurodegenerative diseases the effort to understand the precise pathway that lead to neuronal death is not simply academic. It has major implications in developing new therapies that might actually modify the disease process. By providing a state of the field, it is our hope that this review series will reinvigorate efforts to conduct research that will ultimately answer the question, What kills neurons in neurodegenerative diseases? In each of the reviews, we have asked the authors to not only provide a comprehensive review of the key observations that demonstrate the importance of a specific protein or pathway in neurodegeneration but also highlight the critical next steps needed to shed light on the many enigmatic aspects of neurodegeneration.

Over 20 review articles will appear in this series during 2009. These reviews, published in the open access form in Molecular Neurodegeneration, will allow broad public access. Given the flexibility of this publishing format and the wide range of subject matter that could be addressed, we encourage those wishing to contribute substantive reviews of material not currently covered to contact either of us to discuss a potential submission.
Government plans to improve and clarify public communication of climate science
Authors: A. O'Dowd
Journal: BMJ (2014)

The government has promised to take steps to improve and clarify the communication of climate science to the general public in a newly published official response document.1

In April this year the House of Commons Science and Technology Committee published a critical report after its inquiry into communicating climate science.2 It said that the government was failing to communicate climate science clearly and effectively to the public and that there was little evidence of coordination among government, its agencies, and public bodies on communicating this science, despite various policies to tackle climate change. 

In its official response published on 23 June, the government addressed …
Phosphoprotein enriched in astrocytes (PEA)-15: A potential therapeutic target in multiple disease states
Authors: Fiona H. Greig, Graeme F. Nixon
Journal: Pharmacology & Therapeutics (2014)

Phosphoprotein enriched in astrocytes-15 (PEA-15) is a cytoplasmic protein that sits at an important junction in intracellular signalling and can regulate diverse cellular processes, such as proliferation and apoptosis, dependent upon stimulation. Regulation of these processes occurs by virtue of the unique interaction of PEA-15 with other signalling proteins. PEA-15 acts as a cytoplasmic tether for the mitogen-activated protein kinases, extracellular signal-regulated kinase 1/2 (ERK1/2) preventing nuclear localisation. In order to release ERK1/2, PEA-15 requires to be phosphorylated via several potential pathways. PEA-15 (and its phosphorylation state) therefore regulates many ERK1/2-dependent processes, including proliferation, via regulating ERK1/2 nuclear translocation. In addition, PEA-15 contains a death effector domain (DED) which allows interaction with other DED-containing proteins. PEA-15 can bind the DED-containing apoptotic adaptor molecule, Fas-associated death domain protein (FADD) which is also dependent on the phosphorylation status of PEA-15. PEA-15 binding of FADD can inhibit apoptosis as bound FADD cannot participate in the assembly of apoptotic signalling complexes. Through these protein-protein interactions, PEA-15-regulated cellular effects have now been investigated in a number of disease-related studies. Changes in PEA-15 expression and regulation have been observed in diabetes mellitus, cancer, neurological disorders and the cardiovascular system. These changes have been suggested to contribute to the pathology related to each of these disease states. As such, new therapeutic targets based around PEA-15 and its associated interactions are now being uncovered and could provide novel avenues for treatment strategies in multiple diseases.
Role of Natural Killer Cells in Innate Protection against Lethal Ebola Virus Infection
Authors: Kelly L. Warfield, Jeremy G. Perkins, Dana L. Swenson, Emily M. Deal, Catharine M. Bosio, M. Javad Aman, Wayne M. Yokoyama, Howard A. Young, Sina Bavari
Journal: The Journal of Experimental Medicine (2004)

Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1-3 d before Ebola virus infection rapidly induced protective immunity. VLP injection enhanced the numbers of natural killer (NK) cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets. Unlike wild-type mice, treatment of NK-deficient or -depleted mice with VLPs had no protective effect against Ebola virus infection and NK cells treated with VLPs protected against Ebola virus infection when adoptively transferred to naive mice. The mechanism of NK cell-mediated protection clearly depended on perforin, but not interferon-gamma secretion. Particles containing only VP40 were sufficient to induce NK cell responses and provide protection from infection in the absence of the viral GP. These findings revealed a decisive role for NK cells during lethal Ebola virus infection. This work should open new doors for better understanding of Ebola virus pathogenesis and direct the development of immunotherapeutics, which target the innate immune system, for treatment of Ebola virus infection.