tbuckley/cabot-search huggingface dataset:
Abstract LB-252: Matrix metalloproteinase-2 dysregulate anti-tumor immunity
Authors: Emmanuelle Godefroy, Anne Gallois, Juliana Idoyaga, Francine Jotereau, Nina Bhardwaj
Journal: Cancer Research (2014)

Abstract Background: Cancer cells, including melanoma, can be highly resistant to traditional treatments such as chemotherapy and radiotherapy. As a result, a lot of effort has been put into developing immune therapies to treat cancer patients. The main barrier to design effective immunotherapies is the immunosuppression induced by the tumor. Matrix metalloproteinase-2 (MMP-2) is over-expressed in most cancers including melanoma, and its expression is associated with increased dissemination and poorer survival/prognosis. Here, we not only uncovered an immunosuppressive role of MMP-2 in inducing ineffective/detrimental TH2 immune responses, but also the underlying mechanisms. Methods: Human dendritic cells (DCs) were cultured in the presence of MMP-2 and/or various TLR agonists. DCs responses were monitored using immunostaining, ELISA or cytometric bead array methods. Autologous CD4+ T cells were stimulated using these conditioned tumor-associated antigen (TAA)-pulsed DCs. TAA-specific CD4+ T cells were cloned and characterized using mainly the same techniques as for DCs. Results: Here we showed that MMP-2-conditioned human DCs primed naïve CD4+ T cells to differentiate into an inflammatory TH2 phenotype, i.e. mainly secreting TNFα, IL-4 and IL-13 and expressing GATA3. Accordingly, we detected MMP-2-specific CD4+ T cells displaying the same inflammatory TH2 profile in tumor-infiltrating lymphocytes from melanoma patients. Patients displaying such responses tended to have a poorer survival outcome. We revealed the underlying mechanisms for these T cell skewing: on the one hand, MMP-2 was found to degrade the type-I IFN receptor IFNAR1, thereby preventing STAT1 phosphorylation, which is necessary for IL-12 production. On the other hand, MMP-2 triggers the Toll-like receptor (TLR)-2 on DCs, which leads to NF-κB activation and OX40L expression. Both lack of IL-12 and over-expression of OX40L were found responsible for skewing T cell responses towards a detrimental TH2 phenotype. Conclusions: MMP-2, therefore, acts as an endogenous TH2 “conditioner” and may underlie the prevalence of detrimental TH2 responses in cancer. Our findings also described the responsible MMP-2-dependent mechanisms, which open the way to novel therapeutic strategies and/or targets to skew anti-tumor CD4+ T cell responses towards a more efficient anti-tumor TH1 phenotype to treat cancer patients. Citation Format: Emmanuelle Godefroy, Anne Gallois, Juliana Idoyaga, Francine Jotereau, Nina Bhardwaj. Matrix metalloproteinase-2 dysregulate anti-tumor immunity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-252. doi:10.1158/1538-7445.AM2014-LB-252
The CONSORT Statement-Reply
Authors: Drummond Rennie
Journal: JAMA (1996)

<h3>In Reply.</h3> —We thank Dr Junker and colleagues and Dr Dickinson Ross for their responses to the CONSORT statement. The finding that the quality of reporting of RCTs was similar in German- and English-language journals corroborates other evidence recently reported<sup>1</sup>regarding the methodological quality of reporting of RCTs in several European languages. The fact that the authors did not observe improvements in the quality of reporting of German-language trials over time is surprising and may reflect an insensitive measuring tool. Recent evidence<sup>2</sup>indicates that the quality of reports of RCTs published in a variety of German journals improved over time. We developed the CONSORT statement to improve the quality of reporting of all RCTs regardless of whether they are funded, designed, conducted, or analyzed by the pharmaceutical industry or others. We know of little evidence to support the contention of poorer quality of reporting of RCTs conducted by the pharmaceutical
Changes in CXCL9, CXCL10 and CXCL11 Concentrations after Nasal Allergen Challenge
Authors: D. Tworek, M. Bochenska-Marciniak, I. Kuprys-Lipinska, Z. Kurmanowska, W. Mlynarski, P. Gorski, P. Kuna, A. Antczak
Journal: Journal of Allergy and Clinical Immunology (2011)
Cannabis as medicine: time for the phoenix to rise?
Authors: P. Robson
Journal: BMJ (1998)

Since 1971 British doctors have been barred from prescribing cannabis under the Misuse of Drugs Act. Many otherwise law abiding people have subsequently thought it worthwhile to expose themselves to the risk, inconvenience, and expense of obtaining illegally a drug they believe can ease symptoms inadequately controlled by conventional medicines. Patients have told me how effective cannabis can be in relieving aches and pains, numbing the symptoms of opiate withdrawal, improving sleep, reducing anxiety, and alleviating the vomiting, anorexia, and depression associated with AIDS related disorders. Anecdotes such as these are all very well, but is there any scientific evidence that cannabis has real therapeutic value?

The BMA has addressed this question with an excellent report, which begins by reviewing the pharmacology.1 Only a few of the 60 or so chemicals unique to Cannabis sativa (cannabinoids) have so far been studied, the best known of which is the main psychoactive ingredient, δ-9-tetrahydrocannabinol (THC). Specific cannabinoid receptors in the brain and in spleen macrophages, and naturally …
Transcatheter Aortic Valve Replacement as a Treatment for Late Apicoaortic Conduit Obstruction in a Patient With Severe Aortic Stenosis
Authors: Hani Jneid, Biswajit Kar, David Paniagua, Alvin Blaustein, Lorraine Cornwell, Glenn N. Levine, Nadir Ali, Carlos F. Bechara, Panos Kougias, Prasad V. Atluri, Christopher Pawlak, Blasé Carabello, Biykem Bozkurt, Faisal G. Bakaeen
Journal: Circulation (2013)
Atrial natriuretic peptide mimetics and vasopeptidase inhibitors
Authors: G Sagnella
Journal: Cardiovascular Research (2001)

There is now substantial evidence supporting a role of the natriuretic peptides as a major defence mechanism against excess salt and water retention and high blood pressure. Because of this there has been considerable interest in the therapeutic potential of the natriuretic peptide system. Several approaches have been explored including the use of native peptides, the development of natriuretic peptides mimetics and targetting of endogenous clearance of natriuretic peptides. While ANP and BNP administration may be valuable in some circumstances, however, the limitations of the use of peptides especially for long-term treatment are well apparent. In view of this, considerable effort has been devoted to the development of orally active agents to enhance endogenous natriuretic peptides through inhibition of breakdown by neutral endopeptidase. This research has now led to the vasopeptidase inhibitors — dual inhibitors of both endopeptidase and angiotensin converting enzyme. These agents clearly provide a novel approach to enhance endogenous natriuretic peptide function on a background of reduced angiotensin II activity and may lead to an important advance in the treatment of hypertension and of conditions associated with overt salt and water overload.
Income inequality and 30 day outcomes after acute myocardial infarction, heart failure, and pneumonia: retrospective cohort study
Authors: P. K. Lindenauer, T. Lagu, M. B. Rothberg, J. Avrunin, P. S. Pekow, Y. Wang, H. M. Krumholz
Journal: BMJ (2013)

<b>Objectives</b> To examine the association between income inequality and the risk of mortality and readmission within 30 days of hospitalization. <b>Design</b> Retrospective cohort study of Medicare beneficiaries in the United States. Hierarchical, logistic regression models were developed to estimate the association between income inequality (measured at the US state level) and a patient's risk of mortality and readmission, while sequentially controlling for patient, hospital, other state, and patient socioeconomic characteristics. We considered a 0.05 unit increase in the Gini coefficient as a measure of income inequality. <b>Setting</b> US acute care hospitals. <b>Participants</b> Patients aged 65 years and older, and hospitalized in 2006-08 with a principal diagnosis of acute myocardial infarction, heart failure, or pneumonia. <b>Main outcome measures</b> Risk of death within 30 days of admission or rehospitalization for any cause within 30 days of discharge. The potential number of excess deaths and readmissions associated with higher levels of inequality in US states in the three highest quarters of income inequality were compared with corresponding data in US states in the lowest quarter. <b>Results</b> Mortality analyses included 555 962 admissions (4348 hospitals) for acute myocardial infarction, 1 092 285 (4484) for heart failure, and 1 146 414 (4520); readmission analyses included 553 037 (4262), 1 345 909 (4494), and 1 345 909 (4524) admissions, respectively. In 2006-08, income inequality in US states (as measured by the average Gini coefficient over three years) varied from 0.41 in Utah to 0.50 in New York. Multilevel models showed no significant association between income inequality and mortality within 30 days of admission for patients with acute myocardial infarction, heart failure, or pneumonia. By contrast, income inequality was associated with rehospitalization (acute myocardial infarction, risk ratio 1.09 (95% confidence interval 1.03 to 1.15), heart failure 1.07 (1.01 to 1.12), pneumonia 1.09 (1.03 to 1.15)). Further adjustment for individual income and educational achievement did not significantly attenuate these findings. Over the three year period, we estimate an excess of 7153 (2297 to 11 733) readmissions for acute myocardial infarction, 17 991 (3410 to 31 772) for heart failure, and 14 127 (4617 to 23 115) for pneumonia, that are associated with inequality levels in US states in the three highest quarters of income inequality, compared with US states in the lowest quarter. <b>Conclusions</b> Among patients hospitalized with acute myocardial infarction, heart failure, and pneumonia, exposure to higher levels of income inequality was associated with increased risk of readmission but not mortality. In view of the observational design of the study, these findings could be biased, owing to residual confounding.
IMPACT OF TROPONIN ELEVATION ON OUTCOMES OF PATIENTS WITH ACUTE CORONARY SYNDROMES AND CHRONIC RENAL INSUFFICIENCY
Authors: Subasit Acharji, Eugenia Nikolsky, Giora Weisz, George Dangas, Fredrick Feit, Steven Manoukian, Alexandra J. Lansky, Roxana Mehran, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2010)
Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets
Authors: Amorsolo L Suguitan, Josephine McAuliffe, Kimberly L Mills, Hong Jin, Greg Duke, Bin Lu, Catherine J Luke, Brian Murphy, David E Swayne, George Kemble, Kanta Subbarao
Journal: PLoS Medicine (2006)

Background Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. Methods and Findings Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 106 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. Conclusions The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.
Aircraft Cabin Air Recirculation and Symptoms of the Common Cold
Authors: Jessica Nutik Zitter
Journal: JAMA (2002)

ContextIn recent years, new commercial aircraft have been designed to recirculate approximately 50% of the cabin air to increase fuel efficiency.Some older aircraft use only fresh air.Whether air recirculation increases the transmission of infectious disease is unknown; some studies have demonstrated higher rates of the common cold among persons working in buildings that recirculate air.Objective To evaluate the role of air recirculation as a predictor of postflight upper respiratory tract infections (URIs). Design, Setting, and ParticipantsA natural experiment conducted among 1100 passengers departing the San Francisco Bay area in California and traveling to Denver, Colo, during January through early April 1999, and who completed a questionnaire in the boarding area and a follow-up telephone interview 5 to 7 days later.Fortyseven percent traveled aboard airplanes using 100% fresh air for ventilation, and 53% traveled aboard aircraft that recirculated cabin air.Main Outcome Measure Incidence of reporting new URI symptoms within 1 week of the flight. ResultsPassengers on airplanes that did and did not recirculate air had similar rates of postflight respiratory symptoms.The rates of reporting a cold were 19% vs 21% (P=.34); a runny nose and a cold, 10% vs 11%, (P=.70); and an aggregation of 8 URI symptoms, 3% in both groups (PϾ.99).Results were similar after statistical adjustment for potential confounders. ConclusionWe found no evidence that aircraft cabin air recirculation increases the risk for URI symptoms in passengers traveling aboard commercial jets.
Effect of liver transplantation on QT interval prolongation and autonomic dysfunction in end-stage liver disease
Authors: R Mohamed, P R Forsey, M K Davies, J M Neuberger
Journal: Hepatology (1996)

Both a prolonged QT interval and disturbance of autonomic nervous system function are markers of poor prognosis in patients with diabetes mellitus and alcoholic liver disease (ALD). We studied the prevalence of abnormal QT interval and autonomic nervous system dysfunction in 53 consecutive patients with end-stage liver disease before and after orthotopic liver transplantation (OLT). The maximum QT interval in any lead (QTmax) was assessed by two independent observers. The QTmax, corrected for heart rate (QTcmax) was prolonged in 44 patients (83%), although increased QT dispersion was not found. There was a significant correlation between the QTcmax and Child-Pugh score but not with etiology. Evidence of parasympathetic dysfunction was present in 41 patients (77%), and sympathetic dysfunction was present in 20 patients before OLT. Fifty-two patients underwent transplantation. There was significant improvement in the QTcmax interval after OLT (P < .001); 32 of the 44 patients with prolonged QTcmax ( > 440 milliseconds) improved. Repeat testing was not performed in 7 patients, because they had died or had not undergone transplantation. Indices of parasympathetic function improved in 27 patients after OLT, but no improvement was observed in 8. Improvement in sympathetic dysfunction was observed in 13 of the 19 patients tested. There was no association between QTcmax, autonomic dysfunction, and survival. These results suggest that both prolonged QTcmax and some tests of autonomic function are temporary and arise as a consequence of liver dysfunction.
Relation between troponin T concentration and mortality in patients presenting with an acute stroke: observational study
Authors: P James
Journal: BMJ (2000)

To assess whether a raised serum troponin T concentration would be an independent predictor of death in patients with an acute ischaemic stroke.Observational study.Auckland Hospital, Auckland, New Zealand.All 181 patients with an acute ischaemic stroke admitted over nine months in 1997-8, from a total of 8057 patients admitted to the acute medical service.Blood samples for measuring troponin T concentration were collected 12-72 hours after admission; other variables previously associated with severity of stroke were also recorded and assessed as independent predictors of inpatient mortality.Troponin T concentration was raised (>0.1 microgram/l) in 17% (30) of patients admitted with an acute ischaemic stroke. Thirty one patients died in hospital (12/30 (40%) patients with a raised troponin T concentration v 19/151 (13%) patients with a normal concentration (relative risk 3.2 (95% confidence 1.7 to 5. 8; P=0.0025)). Of 17 possible predictors of death, assessed in a multivariate stepwise model, only a raised troponin T concentration (P=0.0002), age (P=0.0008), and an altered level of consciousness at presentation (P=0.0074) independently predicted an adverse outcome.Serum troponin T concentration at hospital admission is a powerful predictor of mortality in patients admitted with an acute ischaemic stroke.
TREATMENT OF OCULAR DISEASES WITH MERCUROCHROME
Authors: E. R. Chambers
Journal: BMJ (1930)

CASE II.A manl, aged 53.Splenomedullary.Total white count 120,000 per c.mm.At first (April 18th, 1927) good response to deep thlerapy; spleen reduced; gain in weight; count fell to 30,000 per c.mm.By September 3rd, 1928, white count again rose to 105,000 per c.min., and, in spite of further irradiation, was still 164,000 oni Februai-y 20th, 1929.No reaction occurred in 1928 dur ing occa- sionial irradiation, but slight fall of white count recorded after each irradliation.At the beginning of 1929 a steady fall of phagocytes began, until, on November 12tlh, there were less than 1,000 phagocytes per c.mm., and a total wvhite count of 200,000 per c.mm. (myelocytes 40 per cent., polvmorphs 32 per cent., myeloblasts 0.5 per cenit.).Spleen very large.The patient at this poinit became markedly intolerant to deep therapy, and onily medical treatment was possible subsequently.He died early in 1930.CASE IJI.A man, aged 36, witlh typical splenomedullary leuikaemia, was first seen on July 8th, 1929.Total white count 115,000 per c.mm. (miiyelocytes 30 per cenit., polvmorphs 42 per cenit., nearly all pliagocytic).Ftull doses deep tlherapy.White count fell to 8,500 per c.mm., spleen much reduced (September 16th).Three months later white count again rising,9and, in spite of occasional irradia- tion, counit oni March 29th, 1930, was 170,000; spleen very large, marked oedema of legs.Phagocytes now o-nlv 4,000 per c.mm., compared with about 40,000 when first seen.Subsequent irradia- tioIn produced very marked conistitutionial reactioni, vomitinig, and pyrexia.A moderate fall resulted in the white count, but tllis imihecliately r-ose again to 120,000.Evidenitlv response to deep therapy was beginniing to fail, but by usinig smnaller doses of deep therapy-one-quarter usual size-it has been possible up to the time of writing to avoid aerious reaction anid to prevent the wllite count from risinig far above ing the count down as before.CASE IV.M. H., aged 44.Typical spleinomedtullairy case.Total wlhite count 400,000 per c.mm. (myelocytes 42 per cent., polymorphs 30 per cenit.) on June 14th, 1930.Marked oedema and ascites, much loss of weight, complete prostration.Before admission splenic irradiation from Coolidge tube-had produced reaction and some burniis, so discontinued.Wheni admitted, total plhagocytes 90,000 per c.mm.Therefore, in spite of previous reactions, it was decided to give deep therapy in fuill doses.No reactioni followed.On July 12th patient walking, no oedema or ascites, spleen much reduced; white count total .100,000per c.mm., of whiclh 60,000
Immunoglobulin M autoantibody to vimentin intermediate filaments.
Authors: J L Senecal, N F Rothfield, J M Oliver
Journal: Journal of Clinical Investigation (1982)

Serum from a patient with the CREST Syndrome and systemic lupus erythematosus contained an IgM antibody that reacted at dilutions up to 1:800 with a fibrous cytoplasmic network in several epithelioid and fibroblastic cell lines. The antibody was shown by immunofluorescence microscopy to label a specific subset of cytoskeletal polymers, the intermediate filaments. The reactive antigen from this biochemically heterogeneous group of filaments was established as the 58,000-mol wt protein, vimentin: (a) the patient's serum reacts with a range of cell lines that contain intermediate filaments composed of vimentin, but not with cells whose intermediate filaments are composed of different protein subunits; (b) in PTK2 epithelioid cells the serum reacts with the class of filaments that coils around the nucleus after colchicine treatment (vimentin) and not with the filaments that remain dispersed after colchicine (prekeratin); and (c) the component of reactive cells that combines with the serum is shown by immunoelectrophoresis to be a 58,000-mol wt protein antigen. A similar antibody that binds intermediate filaments of PTK2 cells was encountered at lower titer in some sera from other patients with connective tissue diseases and in control sera. Previous routine antinuclear antibody assays using mouse liver or commercially prepared HEp-2 cells have failed to reveal anticytoskeletal antibodies in patient sera, perhaps due to inadequate presentation or preservation of cytoplasmic antigens.