tbuckley/cabot-search huggingface dataset:
Abstract 3324: The endocannabinoid system inhibits non-small cell lung cancer tumorigenesis by modulating the EGF/EGFR pathway
Authors: Janani Ravi, Amita Sneh, Konstantin Shilo, Mohd Nasser, Ramesh Ganju
Journal: Cancer Research (2014)

Abstract Non-small cell lung cancer (NSCLC) is a leading form of cancer with limited treatment regimens and is a major cause of cancer related mortality in the United States. The endocannabinoid system composed of two cannabinoid receptors- CB1 and CB2, their endogenous ligands and the enzymes for their metabolism has been implicated in several pathophysiological conditions. They have been extensively studied in various cancers as inhibitors of tumor cell growth by modulating key cell survival pathways. Anandamide (AEA), a well characterized neurotransmitter is an endogenous cannabinoid and agonist for the cannabinoid receptor CB1. One way to enhance the effect of endocannabinoid signaling is to inhibit the enzyme fatty acid amide hydrolase (FAAH), which metabolizes AEA by using the selective FAAH inhibitor URB597. To understand the physiological role of the endocannabinoid system, the NSCLC cell lines A549 and H460 were treated with either Met-F-AEA, URB597 or in combination and subjected to further analysis. Cells which were incubated in combination with Met-F-AEA and URB597 showed reduced proliferative and chemotactic activities in vitro when compared to AEA alone, which were confirmed by reduced MMP2 secretion and stress fiber formation. Also, we have shown that the combination treatment modulates activation of epidermal growth factor receptor (EGFR) and its downstream targets. In response to EGFR pathway activation, cells treated with Met-F-AEA in combination with URB597 underwent GO/G1 cell cycle arrest, ultimately leading to apoptosis via activation of caspase-9 and PARP. Furthermore, these results were validated in vivo in a xenograft nude mouse model system. Mouse xenografts treated with both Met-F-AEA and URB597 underwent reduction in tumor growth when compared to Met-F-AEA or URB597 alone. In summary, our results presented here show that Met-F-AEA in combination with URB597 inhibits the EGFR pathway, resulting in cell cycle arrest and apoptosis. Our findings suggest a novel perspective for the antitumorigenic activity of the endocannabinoid Met-F-AEA when used in combination with URB597 in NSCLC. Citation Format: Janani Ravi, Amita Sneh, Konstantin Shilo, Mohd Nasser, Ramesh Ganju. The endocannabinoid system inhibits non-small cell lung cancer tumorigenesis by modulating the EGF/EGFR pathway. [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 3324. doi:10.1158/1538-7445.AM2014-3324
P1124 EFFICACY OF TREATMENT WITH PEGYLATED INTERFERON ALFA-2a PLUS RIBAVIRIN IN PRISON INMATES WITH OR WITHOUT PERSONALITY DISORDER. SUBANALYSIS OF THE PERSEO STUDY
Authors: M. Andres, J.J. Anton, P. Sainz de la Hoya, J. de Juan, I. Faraco
Journal: Journal of Hepatology (2014)
Solitary Adenocarcinoma Metastasis Mimicking Sarcomatous Degeneration in Paget's Disease
Authors: GARY R. CONRAD, ALEX W. JOHNSON
Journal: Clinical Nuclear Medicine (1997)

A rare case of mucinous adenocarcinoma presented as a solitary, metastatic deposit to a region of Paget's disease within the peripheral skeleton. Historical, physical, radiographic, and scintigraphic findings were indistinguishable from those of sarcomatous degeneration arising from pagetoid bone. This case supports the idea that when a painful, osteolytic lesion is discovered within a region of Paget's disease, bone scintigraphy has greater value of disclosing potential multifocal or multicentric disease than for providing etiologic specificity for the principal lesion.
Eosinophilia in patients undergoing dialysis.
Authors: J Montoliu, J Lopez-Pedret, L Andreu, L Revert
Journal: BMJ (1981)

oxalate, 10 % magnesium ammonium phosphate, and the remainder calcium phosphate), but she has apparently made no more.Biochemical progress is shown in the figure. ..., ,C:ase 1'Qgg ,2_
Prediction of Mortality by Exercise Echocardiography
Authors: Thomas H. Marwick, Colin Case, Charles Vasey, Susan Allen, Leanne Short, James D. Thomas
Journal: Circulation (2001)

Background —In studies generally involving short follow-up, exercise echocardiography has been shown to predict composite end points. We sought to study the prediction of mortality with this test and to devise a strategy for combination with standard exercise testing. Methods and Results —Clinical, exercise testing, and echocardiographic data were collected in 5375 patients (aged 54±14 years, 3880 men) undergoing exercise echocardiography. The Duke treadmill score was derived from the results of treadmill exercise testing. Resting left ventricular (LV) function and the presence and severity of ischemia were interpreted by expert observers. Follow-up at 10.6 years (mean 5.5±1.9 years) was complete in 5211 patients (97%). The Duke score classified 59% of patients as low risk, 39% as intermediate risk, and 2% as high risk. Resting LV dysfunction was present in 1445 patients (27%), and the exercise echocardiogram was abnormal in 2525 patients (47%). Death occurred in 649 patients (12%). Over the first 6 years of follow-up, those with normal exercise echocardiograms had a mortality of 1% per year. Ischemia was an independent predictor of mortality. In sequential Cox models, the predictive power of clinical data was strengthened by adding the Duke score, resting LV function, and the results of exercise echocardiography. Exercise echocardiography was able to substratify patients with intermediate-risk Duke scores into groups with a yearly mortality of 2% to 7%. Conclusions —A normal exercise echocardiogram confers a low risk of death, and positive results are an independent predictor of death; ischemia is incremental to other data. This test may be particularly useful in patients with intermediate-risk Duke treadmill scores.
Left Ventricular Volumes and Ejection Fraction by Echocardiography
Authors: JOAQUIN F. POMBO, BART L. TROY, RICHARD O. RUSSELL
Journal: Circulation (1971)

Left ventricular end-diastolic and end-systolic volume, stroke volume, and ejection fraction were determined by biplane angiocardiography and echocardiography in 27 patients suspected of having heart disease. Angiographic volumes were calculated by the area-length method and echocardiographic volumes, from the left ventricular dimension of the echograms. The angiographic minor diameter and the semilength correlated significantly with the echocardiographic left ventricular dimensions in diastole and systole. Left ventricular size over a wide range compared favorably by each technique, with a correlation coefficient of r = 0.97 for end-diastolic volume (range by angiography 80-585 ml, see ± 27.76), r = 0.97 for end-systolic volume (range by angiography 24-485 ml, see ± 23.64), r = 0.83 for total left ventricular stroke volume (range by angiography 35-229 ml, see ± 25.45), and r = 0.80 for left ventricular ejection fraction (range by angiography 0.18-0.70, see ± 0.09). These data indicate that left ventricular dimensions in systole and diastole can be reliably determined and left ventricular chamber size and ejection fraction can be quantitated in man by the noninvasive technique of echocardiography.
Hype from journalists and scientists
Authors: A. Ballantyne
Journal: BMJ (1992)

<h3>ABSTRACT</h3> <h3>Background</h3> Patients with severe COVID-19 seem to have a compromised antiviral response and hyperinflammation. Neutrophils are critical players in COVID-19 pathogenesis. IL-17A plays a major role in protection against extracellular pathogens and neutrophil attraction and activation. We hypothesized that secukinumab, an anti-IL17A monoclonal antibody, could mitigate the deleterious hyperinflammation in COVID-19. <h3>Methods</h3> BISHOP was an open-label, single-center, phase-II controlled trial. Fifty adults hospitalized Covid-19 patients, confirmed by a positive SARS-CoV-2 RT-PCR, were randomized 1:1 to receive 300mg of secukinumab subcutaneously at day-0 (group A) plus standard of care (SoC: antiviral drugs, antimicrobials, corticosteroids, and/or anticoagulants) or SoC alone (group B). A second dose of 300mg of secukinumab could be administered on day-7, according to staff judgment. The primary endpoint was ventilator-free days at day-28 (VFD-28). Secondary efficacy and safety outcomes were also explored. <h3>Findings</h3> An intention-to-treat analysis showed no difference in VFD-28: 23.7 (95%CI 19.6-27.8) in group A vs. 23.8 (19.9-27.6) in group B, p=0.62; There was also no difference in hospitalization time, intensive care unit demand, the incidence of circulatory shock, acute kidney injury, fungal or bacterial co-infections, and severe adverse events. Pulmonary thromboembolism was less frequent in group A (4.2% vs. 26.2% p=0.04). There was one death in each group. Viral clearance, defined by the viral load fold change (2-ΔΔCT) in upper airways, between day-0 and day-7, was also similar: 0.17 (0.05-0.56) in group A vs. 0.24 (0.10-0.57) in group B. <h3>Interpretation</h3> The efficacy of secukinumab in the treatment of Covid19 was not demonstrated. No difference between groups in adverse events and no unexpected events were observed. <h3>Funding</h3> Novartis Brazil supported this research providing expert input in the development of the project, drug supply, data management, and monitoring.
Estimating cancer risks to a population.
Authors: M A Schneiderman, C C Brown
Journal: Environmental Health Perspectives (1978)

Three important issues impinge on estimating the risk of cancer to a population: (1) How can one use epidemiologic studies on one population to tell us what is likely to happen to other populations? (2) How can one use nonhuman data (i.e., laboratory experiments) to tell us what is likely to happen to humans? (3) What reasonable assumptions can be used to guide the logical extension of information from the laboratory to expectations for man, and what research is needed to support or modify these assumptions? Four principles currently guide our laboratory-to-man extrapolations: effects in animals, properly qualified, are applicable to man; methods do not now exist to establish a threshold for long-delayed effects such as cancer; the exposure of experimental animals to high doses is a necessary and valid method of discovering possible carcinogenic hazards in man; materials should be assessed in terms of human risk rather than as
Invasive Meningococcal Conjunctivitis
Authors: Fernando A. Moraga
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Systemic meningococcal infections are presumed to follow spread of meningococci from the nasopharynx into the blood and then to the cerebrospinal fluid.<sup>1</sup>However, there have been reports of at least 10 cases of systemic meningococcal infection in which the conjunctiva was the probable portal of entry.<sup>2-11</sup>The overall incidence of invasive meningococcal conjunctivitis has been estimated to be about 10% of the cases of primary meningococcal conjunctivitis.<sup>12</sup> <i>Neisseria meningitidis</i>was isolated from conjunctival exudate in 21 patients with acute bacterial conjunctivitis who were treated at our hospital during the last 5 years. During this period, 1030 patients with a microbiologically proved acute bacterial conjunctivitis were diagnosed, which gives an incidence for<i>N meningitidis</i>conjunctivitis of 2.0%. Six (28.6%) of our 21 patients with primary meningococcal conjunctivitis, after a mean interval of 27.1 (±23.8) hours from the appearance of the initial ocular symptoms, developed systemic
PRODUCTION OF THE SHWARTZMAN PHENOMENON BY A SINGLE-INJECTION TECHNIC
Authors: B. Black-Schaffer, J. W. Milam, D. D. Brockman, E. V. Coonrad, S. B. Silverman
Journal: The Journal of Experimental Medicine (1950)

In the hypersensitive animal a single inoculation of homologous antigen mixed with Shwartzman preparatory toxin may lead to the production of a Shwartzman reaction which functions as an amplifier of the antigen-antibody tissue response. The combination of antigen and bacterial toxin does not alter the antigenicity of purified bovine gamma globulin. This form of the Shwartzman phenomenon may be useful in the investigation of hyperergic tissue reactions.
GP covered out of hours service in London from home in Norfolk
Authors: C. Dyer
Journal: BMJ (2012)

A doctor who earned more than £200 000 (€240 000; $314 000) a year running an out of hours GP service in southwest London while also in full time practice as a GP failed to visit patients when he was on a weekend rota because he was at his second home 225 km away in Norfolk.

Ravi Sondhi also took an unauthorised £100 000 from the out of hours service, Croydoc, for his own purposes and organised overnight rotas so that he and the other doctors who did them got a full night’s pay for working only one third of the rota each night. Unknown to the primary care trusts’ contract managers who used the service, there was …
Oncolytic vaccinia therapy of squamous cell carcinoma
Authors: Zhenkun Yu, Sen Li, Peter Brader, Nanhai Chen, Yong A Yu, Qian Zhang, Aladar A Szalay, Yuman Fong, Richard J Wong
Journal: Molecular Cancer (2009)

Abstract Background Novel therapies are necessary to improve outcomes for patients with squamous cell carcinomas (SCC) of the head and neck. Historically, vaccinia virus was administered widely to humans as a vaccine and led to the eradication of smallpox. We examined the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68) as an oncolytic agent against a panel of six human head and neck SCC cell lines. Results All six cell lines supported viral transgene expression (β-galactosidase, green fluorescent protein, and luciferase) as early as 6 hours after viral exposure. Efficient transgene expression and viral replication (&gt;150-fold titer increase over 72 hrs) were observed in four of the cell lines. At a multiplicity of infection (MOI) of 1, GLV-1h68 was highly cytotoxic to the four cell lines, resulting in ≥ 90% cytotoxicity over 6 days, and the remaining two cell lines exhibited &gt;45% cytotoxicity. Even at a very low MOI of 0.01, three cell lines still demonstrated &gt;60% cell death over 6 days. A single injection of GLV-1h68 (5 × 10 6 pfu) intratumorally into MSKQLL2 xenografts in mice exhibited localized intratumoral luciferase activity peaking at days 2–4, with gradual resolution over 10 days and no evidence of spread to normal organs. Treated animals exhibited near-complete tumor regression over a 24-day period without any observed toxicity, while control animals demonstrated rapid tumor progression. Conclusion These results demonstrate significant oncolytic efficacy by an attenuated vaccinia virus for infecting and lysing head and neck SCC both in vitro and in vivo , and support its continued investigation in future clinical trials.
Nitric Oxide Modulates Synaptic Vesicle Docking/Fusion Reactions
Authors: Mollie K Meffert, Nicole C Calakos, Richard H Scheller, Howard Schulman
Journal: Neuron (1996)

Nitric oxide (NO) stimulates calcium-independent neurotransmitter release from synaptosomes. NO-stimulated release was found to be inhibited by Botulinum neurotoxins that inactivate the core complex of synaptic proteins involved in the docking and fusion of synaptic vesicles. In experiments using recombinant proteins, NO donors increased formation of the VAMP/SNAP-25/syntaxin 1a core complex and inhibited the binding of n-sec1 to syntaxin 1a. The combined effects of these activities is predicted to promote vesicle docking/fusion. The sulfhydryl reagent NEM inhibited the binding of n-sec1 to syntaxin 1a, while β-ME could reverse the NO-enhanced association of VAMP/SNAP-25/syntaxin 1a. These data suggest that post-translational modification of sulfhydryl groups by a nitrogen monoxide (likely to be NO+) alters the synaptic protein interactions that regulate neurotransmitter release and synaptic plasticity.
Transfer of immediate hypersensitivity and airway hyperresponsiveness by IgE-positive B cells.
Authors: G Lack, A Oshiba, K L Bradley, J E Loader, D Amran, G L Larsen, E W Gelfand
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The role of allergen-specific sIgE+ B cells in the development of airway hyperresponsiveness to electrical field stimulation was examined in a murine model of allergic sensitization. Ovalbumin (OVA)-specific B cells (OVA+) were isolated from mice that were sensitized to aerosolized OVA. The OVA+ B cell population was shown to be distinct from the remaining, non-OVA-responsive B cells (OVA-). There was a high frequency of sIgE+ B cells and a low frequency of sIgG+ B cells in the OVA+ population compared with the OVA- population, where the ratio was reversed. Although both populations produced immunoglobulin in vitro, only the OVA+ cells secreted anti-OVA antibodies. Transfer of 10(6) OVA+ B cells or as few as 5 x 10(4) OVA+/sIgE+ B cells was able to transfer the capability for anti-OVA IgE synthesis and cutaneous reactivity to OVA in naive recipients. Exposure to OVA via the airways in addition to transfer of OVA+ B cells was necessary for development of airway hyperresponsiveness, whereas recipients challenged with an irrelevant allergen, ragweed, had normal airway function. Transfer of up to 10(7) OVA- B cells failed to induce production of anti-OVA IgE. Despite production of polyclonal IgE, recipients of OVA- B cells did not develop airway hyperresponsiveness after OVA challenge. We conclude that both allergen-specific IgE production and local challenge via the airways with specific allergen are necessary to change airway function in this model.
Evaluation of the effectiveness of mass screening for uterine cancer in Japan: the potential years of life lost.
Authors: T Kuroishi, K Hirose, S Tominaga
Journal: Environmental Health Perspectives (1990)

To evaluate the effectiveness of mass screening for uterine cancer in Japan, we compared the changes in the age-adjusted rates of potential years of life lost (PYLL) due to uterine cancer between 1969 and 1972 to 1973 through 1977 between the high coverage-rate (intensively screened) areas and the comparable control areas. The percent reduction in the average age-adjusted rate of PYLL due to uterine cancer and the years of life saved per 100,000 females were greater in the high coverage-rate areas than in the control areas. These results suggested that mass screening programs for uterine cancer contribute to saving years of life.
Bacterial translocation of enteric organisms in patients with cirrhosis
Authors: Isabel Cirera, Tilman Martin Bauer, Miguel Navasa, Jordi Vila, Luis Grande, Pilar Taurá, Josep Fuster, Juan Carlos Garcı́a-Valdecasas, Antonio Lacy, Marı́a Jesús Suárez, Antoni Rimola, Juan Rodés
Journal: Journal of Hepatology (2001)
Thesaurosis Caused by Hair Spray-Reply
Authors: Martin Bergmann
Journal: JAMA (1961)

<h3>To the Editor:—</h3> Thank you for giving me the opportunity of commenting on Dr. Brunner's letter. On the basis of our studies we are satisfied that the editorial inThe Journalwas correct and that there is such an entity as thesaurosis or storage disease due to inhalation of hair spray. In regard to the specific points raised in the letter, we would like to answer as follows: The resemblance of the lymph node lesions to sarcoidosis is indeed striking and has been confirmed by us in other cases. In the lung the histologic picture as found in as yet unpublished cases resembles that seen in so-called Hamman-Rich syndrome. The differentiating histologic feature in both areas is the presence of ingested PAS-positive material in macrophages. As a dermatologist, Dr. Brunner may perhaps be unaware of current concepts of etiology of both these syndromes. It is generally held that they
Phytohaemagglutinin induced proliferation of lymphocytes from patients with rheumatoid arthritis and iron deficiency.
Authors: R J Polson, A Bomford, H Berry, R Williams
Journal: Annals of the Rheumatic Diseases (1988)

The response of peripheral blood lymphocytes to stimulation by mitogens such as phytohaemagglutinin (PHA) is commonly depressed in both rheumatoid arthritis and iron deficiency, and as many rheumatoid patients are anaemic with evidence of abnormal iron metabolism it is possible that the same mechanism underlies the observed suppression in both conditions. In the present study the mitogenic response to PHA of lymphocytes from three rheumatoid patients, who were also iron deficient, and two healthy controls has been shown to be significantly less in iron deficient than iron containing media (p less than 0.001). In addition, iron deficient sera from these patients reduced the PHA induced proliferation of lymphocytes from a normal subject (p less than 0.01), an effect which was prevented by prior addition of iron to these serum samples. In iron containing media lymphocytes from five patients and two controls showed no difference in their response to PHA for both the minimum mitogen concentration which enhanced transformation and the peak [3H]thymidine uptake; but patients9 lymphocytes showed significantly less response to PHA concentrations of 5 and 10 mg/l (p less than 0.02), resulting in a reduction in the area under the dose response curves up to 20 mg/l (p less than 0.05). These findings show both that iron deficient sera can impair PHA induced lymphocyte transformation and that lymphocytes from iron deficient rheumatoid patients have impaired responsiveness to PHA. Iron is known to be required intracellularly for the enzyme ribonucleotide reductase, which is important for DNA synthesis, and reduced activity of this enzyme could explain these observed effects.
Effects of methotrexate on cartilage metabolism
Authors: G. CARROLL, M. BELL;, J. NEIDEL, L. SOVA
Journal: Annals of the Rheumatic Diseases (1999)

We read with interest the report by Neidal et al 1 on the effects of methotrexate (MTX) on articular cartilage in vitro and in vivo. The relevance of these findings to patients with rheumatoid arthritis (RA) and other diseases who are receiving MTX is of considerable interest.

In a previous study2 we reported that treatment of RA patients with MTX resulted in reduced numbers of leucocytes and reduced concentrations of interleukin 1β (IL1β) in the synovial fluid (SF) relative to placebo control patients.

Sequential specimens of SF were available in four control patients and in eight patients treated with MTX who participated in that study.2 The SF keratan sulphate concentrations at baseline and at days 7, 28, and 56 were determined as previously described3 and are shown in figure 1. A progressive and statistically significant reduction in SF keratan sulphate was observed in the MTX group (mean (SEM) 206 …