tbuckley/cabot-search huggingface dataset:
Cabozantinib Suppresses Tumor Growth and Metastasis in Hepatocellular Carcinoma by a Dual Blockade of VEGFR2 and MET
Authors: Qingfeng Xiang, Weiqiang Chen, Meng Ren, Jingnan Wang, Hongwu Zhang, David Y.B. Deng, Lei Zhang, Changzhen Shang, Yajin Chen
Journal: Clinical Cancer Research (2014)

MET signaling has been suggested a potential role in hepatocellular carcinoma (HCC) and associated with prometastasis during antiangiogenesis therapy. We investigated the potential association between MET expression and therapeutic response to sorafenib in patients with HCC. Antitumor effects of cabozantinib, a dual inhibitor of MET and VEGFR2, were examined in cultured HCC cells as well as in vivo models.Total MET and phosphorylated MET (p-MET) were measured in 29 resected HCC specimens, and correlated with response to sorafenib as postoperative adjuvant therapy. In the second set of experiments using cultured HCC cells, and mouse xenograft and metastatic models, effects of cabozantinib were examined.High level of p-MET in resected HCC specimens was associated with resistance to adjuvant sorafenib therapy. In cultured HCC cells that expressed p-MET, cabozantinib inhibited the activity of MET and its downstream effectors, leading to G1-phase arrest. Cabozantinib inhibited tumor growth in p-MET-positive and p-MET-negative HCC by decreasing angiogenesis, inhibiting proliferation, and promoting apoptosis, but it exhibited more profound efficacy in p-MET-positive HCC xenografts. Cabozantinib blocked the hepatocyte growth factor (HGF)-stimulated MET pathway and inhibited the migration and invasion of the HCC cells. Notably, cabozantinib reduced the number of metastatic lesions in the lung and liver in the experimental metastatic mouse model.Patients with HCC with high level of p-MET are associated with resistance to adjuvant sorafenib treatment. The dual blockade of VEGFR2 and MET by cabozantinib has significant antitumor activities in HCC, and the activation of MET in HCC may be a promising efficacy-predicting biomarker. Clin Cancer Res; 20(11); 2959-70. ©2014 AACR.
FDA's science board says the plastics chemical bisphenol A gives reason for concern
Authors: J. H. Tanne
Journal: BMJ (2008)

The US Food and Drug Administration has been criticised by its full science board regarding the risks to health from bisphenol A and was told to reconsider the safety of the chemical, which is used to harden plastic in baby bottles and is found in the linings of tin cans and other consumer products. The board supported a report of its subcommittee that raised concerns about the chemical. It said the FDA had made a number of errors. It had:
A8.26 Bortezomib ameliorates the disease progression due to ovalbumin immunisation in NZB/W F1 lupus prone mice
Authors: L Khodadadi, Q Cheng, O Winter, A Taddeo, A Radbruch, BF Hoyer, F Hiepe
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Plasma cell depletion with bortezomib can prevent the development of lupus nephritis and prolong survival in NZB/W mice. Here, we studied the effect of the immunisation with OVA in combination with bortezomib on the disease in NZB/W mice. <h3>Methods</h3> NZB/W F1 female mice 16 week-old (early disease stage) were divided into 3 groups as follows: 1. Non-immunised mice as a control group, 2. Immunised mice; mice immunised with alum-precipitated OVA i.p and boosted 3 weeks after primary immunisation, 3. Immunised mice as group 2 receiving two shots of bortezomib (0.75 mg/kg, i.v) at 48 and 12 h before secondary immunisation. The numbers of anti-dsDNA antibody secreting cells (ASCs) were assessed in spleen and bone marrow by ELISPOT one month after secondary immunisation. Moreover we investigated serologic parameters including anti-OVA and anti-dsDNA antibody levels by ELISA as well as proteinuria and survival rate. <h3>Results</h3> Immunised mice (group 2) developed proteinuria, which occurred earlier and stronger than in the non-immunised mice and in mice additionally treated with Bz before booster immunisation (group 3). Survival rate of immunised mice was reduced in comparison to group 3 treated with Bz while group 1 showed the longest survival. Autoantibody levels in group 2 and 3 were higher than in the control group 1. Mice immunised with OVA showed a tendency to higher numbers of IgM anti-dsDNA ASCs in the bone marrow and spleen than in non-immunised mice while IgG anti-dsDNA ASCs counts analysed in mice immunised with OVA and treated with Bz, were comparable with their counts in non-immunised mice. The Bz treatment before the secondary OVA immunisation resulted in lower anti-OVA antibody levels than in immunised mice without Bz treatment. <h3>Conclusion</h3> Immunisation with alum-precipitated OVA accelerates autoimmunity in NZB/W mice. This effect can be ameliorated by plasma cell depletion with bortezomib.
Identification of dimenhydrinate as the causative agent in fixed drug eruption using patch‐testing in previously affected skin
Authors: None Smola, None Kruppa, None Hunzelmann, None Krieg, None Scharffetter‐Kochanek
Journal: British Journal of Dermatology (1998)

Journal Article Identification of dimenhydrinate as the causative agent in fixed drug eruption using patch‐testing in previously affected skin Get access Smola, Smola Department of Dermatology, University of Cologne, Joseph‐Stelzmann‐Str. 9, 50924 Köln, Germany Search for other works by this author on: Oxford Academic Google Scholar Kruppa, Kruppa Department of Dermatology, University of Cologne, Joseph‐Stelzmann‐Str. 9, 50924 Köln, Germany Search for other works by this author on: Oxford Academic Google Scholar Hunzelmann, Hunzelmann Department of Dermatology, University of Cologne, Joseph‐Stelzmann‐Str. 9, 50924 Köln, Germany Search for other works by this author on: Oxford Academic Google Scholar Krieg, Krieg Department of Dermatology, University of Cologne, Joseph‐Stelzmann‐Str. 9, 50924 Köln, Germany Search for other works by this author on: Oxford Academic Google Scholar Scharffetter‐Kochanek Scharffetter‐Kochanek Department of Dermatology, University of Cologne, Joseph‐Stelzmann‐Str. 9, 50924 Köln, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 138, Issue 5, 1 May 1998, Pages 920–921, https://doi.org/10.1046/j.1365-2133.1998.02248.x Published: 01 May 1998
Foreign Medical Graduates and the Issue of Substantial Disruption of Medical Services
Authors: Peter O. Way, Lynn E. Jensen, Louis J. Goodman
Journal: New England Journal of Medicine (1978)

Provisions of the 1976 Health Professions Educational Assistance Act may result in a substantial disruption of medical services provided by foreign medical graduates in United States residency training programs. Estimates of the effect of the Act indicate that between one third and two thirds of foreign graduates receiving visas annually will not qualify for admission, under the new provisions. Results of a recent study show, furthermore, that foreign medical graduates constitute a majority of the residents in 23 per cent of the hospitals with residency programs. Transition to a decreased dependence on foreign graduates may be facilitated through the waiver of two provisions relating to exchange visitors. Projected numbers of United States medical graduates and citizens receiving medical education abroad will not be enough to fill the gap created by the ultimate reduction in alien physicians. United States residency programs will have to develop alternative sources of residents to continue operating at current levels.
Psychiatric and Entomological Aspects of Delusory Parasitosis
Authors: Albert H. Schrut
Journal: JAMA (1963)

PROBLEMS involving arthropods and emotionallydisturbed persons have long been known to the medical and entomological professions. The purpose of this paper is to discuss a phase of this medico-entomological problem which often is puzzling and exasperating. It is hoped that the reader will be better able to understand and tolerate the complaints which are often misunderstood and thereby direct the patient to proper medical care. Wilson and Miller,<sup>1</sup>and Obermayer,<sup>2</sup>have applied the term "delusions of parasitosis" to those patients who have an unshakeable belief that live organisms, such as mites or insects, are present in the skin. This aberration often results in a severe pruritic condition, which, through scratching, may cause extensive excoriation and scarring. The first awareness of a problem may arise when the patient confronts the entomologist with material that allegedly contains insect specimens which were scraped or plucked off the skin, clothing, furniture, cosmetics,
Device gauges anesthetized patient's brain O2
Authors: Catherine Macek
Journal: JAMA (1982)

A new noninvasive device for monitoring cerebral oxygen levels in surgical patients under general anesthesia can detect within seconds changes in oxygen supply to the brain, according to Duke University School of Medicine researchers. The NIROS-SCOPE (Near-InfraRed Oxygen Sufficiency Scope) is the brainchild of Frans F. Jöbsis vander Vliet, PhD, professor of physiology at Duke in Durham, NC. Although he first conceived the idea more than 25 years ago, it was not until recently that technological advances in lasers, fiberoptics, and microprocessors finally "set the stage for development of a new instrument for clinical use," Jöbsis says. The system primarily reflects any changes in utilization of oxygen by brain cells, and there is presently no other method of doing this. The apparatus consists of a light source containing several lasers, each producing light of a different near-infrared (IR) monochromatic wavelength; two fiberoptic bundles that attach to either side of the
Medical Uses of Vitamin E
Authors: John G. Bieri, Laurence Corash, Van S. Hubbard
Journal: New England Journal of Medicine (1983)

This review discusses the rationale for vitamin E therapy in medical conditions in which the vitamin may have positive clinical effects. It should be recognized at the outset that nutritional inadequacy or frank deficiency of vitamin E is found only in patients with various genetic or acquired diseases, with the exception of premature children, in whom the deficiency may be iatrogenous. In the adult conditions in which vitamin E has a claimed efficacy, an unknown pharmacologic effect unrelated to the normal functioning of the vitamin is probably involved.Distribution and Dietary IntakeVitamin E is one of the most widely . . .
Insulin secretion to glucose as well as nonglucose stimuli is impaired in spontaneously diabetic Nagoya-Shibata-Yasuda mice
Authors: Yoichi Hamada, Hiroshi Ikegami, Hironori Ueda, Yoshihiko Kawaguchi, Eiji Yamato, Koji Nojima, Kazunori Yamada, Naru Babaya, Masao Shibata, Toshio Ogihara
Journal: Metabolism (2001)
STUDIES ON THE EFFECT OF CERTAIN MACROMOLECULAR SUBSTANCES ON THE RESPIRATORY ACTIVITY OF THE LEUCOCYTES OF PERIPHERAL BLOOD
Authors: Bella S. Strauss, Chandler A. Stetson
Journal: The Journal of Experimental Medicine (1960)

The oxygen, uptake of lightly heparinized human blood was found to increase markedly upon the addition of bacterial endotoxins, soluble antigen-antibody complexes, or polystyrene latex particles. The effect apparently reflects a transitory stimulation of respiratory activity of the blood leucocytes. The effect did not occur in the presence of anticoagulant amounts of citrate or ethylenediaminetetraacetate, was inhibited by iodoacetate and fluoride ions, and may be related to the energy-yielding processes involved in histamine release or phagocytosis.
Genetically engineered lymphocytes in metastatic melanoma: TIL 1383I TCR transduced T-cells are detectable after infusion
Authors: Courtney Regan, Michael Nishimura, Ann Lau Clark, Kelly Moxley, Gina Scurti, Vladimir Slepushkin, Andre Roy, Kathy Schonely, Boro Dropulic, Joseph Clark
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Previous studies in adoptive T-cell transfer have suggested that persistence of the transduced T-cells is central to making this therapy a viable option. Understanding the behavior of tumor-reactive T-cells in cancer patients and measuring persistence are two objectives in a phase
Phase 1 Study of Stereotactic Body Radiotherapy and Interleukin-2—Tumor and Immunological Responses
Authors: Steven K. Seung, Brendan D. Curti, Marka Crittenden, Edwin Walker, Todd Coffey, Janet C. Siebert, William Miller, Roxanne Payne, Lyn Glenn, Alexandru Bageac, Walter J. Urba
Journal: Science Translational Medicine (2012)

Stereotactic body radiation therapy enhances tumor response rate to high-dose interleukin-2 in a phase 1 study.
Prevalence of Tuberculin Positivity and Skin Test Anergy in HIV-1—Seropositive and —Seronegative Intravenous Drug Users
Authors: Neil M. H. Graham, Kenrad E. Nelson, Liza Solomon, Margaret Bonds, Rosetta T. Rizzo, Joseph Scavotto, Jacqueline Astemborski, David Vlahov
Journal: JAMA (1992)

<h3>Objectives.</h3> —To identify differences in purified protein derivative (PPD) tuberculin positivity and skin test anergy rates by human immunodeficiency virus (HIV) serostatus, CD4<sup>+</sup>lymphocyte count, and other risk factors in intravenous drug users (IVDUs); and to evaluate the appropriateness of the Centers for Disease Control (CDC)—recommended definition for a positive PPD tuberculin skin test result in HIV-1—seropositive patients. <h3>Design.</h3> —Nested case-control and cross-sectional analyses. <h3>Setting.</h3> —Community-based cohort of IVDUs. <h3>Patients.</h3> —Two hundred sixty HIV-1—seropositive and —seronegative IVDUs, drawn from an unselected cohort, were skin-tested for sensitivity to PPD tuberculin, mumps, and<i>Candida</i>antigens using the Mantoux method. <h3>Outcome Measures.</h3> —Positivity to PPD tuberculin, skin test anergy. <h3>Results.</h3> —Even using the CDC definition of an induration 5 mm or greater in diameter in HIV-1 seropositives, this group was substantially less likely to be PPD tuberculin positive than HIV-1 seronegatives (13.8% vs 25.2%;<i>P</i>=.02). In the HIV-1 seropositives the relative odds of being PPD positive varied depending on whether 10 mm or greater (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.2 to 0.7), 5 mm or greater (OR, 0.5; 95% CI, 0.2 to 0.9), or 2 mm or greater (OR, 0.7; 95% CI, 0.4 to 1.3) was used to define a positive test result. The mean diameter induration in the HIV-1—seropositive group was 2.6 mm vs 5.4 mm in the seronegative group (<i>P</i>=.005). Skin test anergy (to mumps and<i>Candida</i>) appeared to explain the differential. Anergy was substantially higher in the HIV-1 seropositive group and increased as the CD4<sup>+</sup>lymphocyte count fell (χ<sup>2</sup>for linear trend, 24.5;<i>P</i>&lt;.0001). An inverse linear trend for PPD positivity and CD4<sup>+</sup>lymphocyte count was also observed (χ<sup>2</sup>for trend, 6.1;<i>P</i>=.01). In multivariate analyses, being 35 years of age or older and being HIV-1 seronegative were significantly associated with PPD positivity, while history of previous police arrest was of borderline significance. Only HIV-1 seropositivity was significantly associated with anergy. <h3>Conclusions.</h3> —There findings show that CDC-recommended definition of an induration 5 mm or greater in diameter for PPD tuberculin positivity in HIV-1 seropositives significantly underestimates the "true" infection rate (using the PPD positivity rate in HIV-1 seronegatives as the criterion standard). A definition of 2 mm or greater would appear to be a better cutoff for reducing misclassification in HIV-1 seropositives. This study also confirms that delayed-type hypersensitivity is seriously depressed in HIV-1 seropositive IVDUs and that anergy testing is mandatory to properly assess a negative PPD test result. (<i>JAMA</i>. 1992;267:369-373)
Role of combination antiviral therapy in pandemic influenza and stockpiling implications
Authors: Sotirios Tsiodras, John D Mooney, Angelos Hatzakis
Journal: BMJ (2007)

It is impossible to predict which drugs will be effective against a new pandemic strain of influenza. <b>Sotirios Tsiodras</b><b>and colleagues</b> argue that failure to stockpile both major classes of antiviral drugs could prove costly
Screen all pregnant women for risk factors for gestational diabetes, says NICE
Authors: Zosia Kmietowicz
Journal: BMJ (2008)

Doctors and midwives are being asked to screen all pregnant women for risk factors for gestational diabetes at their first booking appointment and to offer them a test for the condition if their risk is raised.

The recommendation is included in the revised guidance from the National Institute for Health and Clinical Excellence on the routine care that should be offered to all pregnant women in England, which was first published in 2003.

Risk factors for gestational diabetes include a body mass index greater than 30; previous macrosomic baby above 4.5 kg; previous gestational diabetes; family history of diabetes; and family origin with high prevalence of diabetes, such as South Asian, black Caribbean, and Middle Eastern.

The guidance also says that the combined test to screen for Down’s syndrome (nuchal translucency, β human chorionic gonadotrophin, and pregnancy associated plasma protein A) should be offered earlier whenever possible—at between 11 …
"Sorry, you won't be able to see this..."
Authors: B. Dixon
Journal: BMJ (1996)

Fuelled by recent bitter sweet experience at a scientific conference, I return to a topic which I ventilated about two years ago in this column. Things have not improved since then, so let's try again.

The first speaker after lunch began in a soulless monotone, addressed the screen, and extinguished any residual inclination for the audience to remain awake by using unreadable overheads. The second speaker was slightly brighter, but presented visuals which were even worse than the previous lot.

Then something remarkable occurred. Unlike her predecessors, the next speaker looked at the audience, said good afternoon, and began with a slide that was clear, simple, and colourful. It received an immediate, …
Life threatening acute pneumonitis during low dose methotrexate treatment for rheumatoid arthritis: a case report and review of the literature.
Authors: M G Ridley, C S Wolfe, J A Mathews
Journal: Annals of the Rheumatic Diseases (1988)

A patient is described with definite rheumatoid arthritis (RA) who developed life threatening acute pneumonitis after receiving a total dose of only 12.5 mg methotrexate (MTX). This complication has been previously described, but this is probably the lowest reported dose before development of pneumonitis in a patient with RA. The possible significance of this case is discussed in the light of recent reports suggesting an increased susceptibility of patients with RA to the pulmonary toxicity of MTX.
The biosynthesis of adrenal steroids: effects of angiotensin II, adrenocorticotropin, and potassium.
Authors: N M Kaplan
Journal: Journal of Clinical Investigation (1965)

The search for the physiologic mechanism con- trolling the biosynthesis of aldosterone has centered upon three factors-ACTH, the renin-angiotensin 1 system, and potassium.All three have been shown to stimulate the production of aldosterone in the intact animal (1-4).Despite a large num- ber of in vivo experiments involving ,the rat, dog, sheep, and man, the exact locus of each stimulus within the control mechanism and the precise rela- tionships of one to the other have not been clearly defined.In particular, disagreement persists as to the physiologic role of the renin-angiotensin sys- tem (2, 3, 5).The initial results of in vitro studies of the ef- fects of ACTH and angiotensin on the biosynthe- sis of adrenal steroids have been published (6).In those studies, in which the effects upon aldosterone and cortisol were nonselective, relatively large amounts of both agents were used.Additional in vitro experiments have therefore been performed, studying the effects of smaller amounts of these agents as well as potassium, alone and in combination, in an attempt to elucidate further their role in the control of aldosterone biosyn- thesis.
A RANDOMIZED, OPEN-LABELED, MULTICENTER TRIAL FOR SAFETY AND EFFICACY OF INTRACORONARY ADULT HUMAN MESENCHYMAL STEM CELLS AFTER ACUTE MYOCARDIAL INFARCTION
Authors: Jun-won Lee, Sung-Gyun Ahn, Jang-Young Kim, Byung-Su Yoo, Seung-Hwan Lee, Junghan Yoon, Kyung-Hoon Choe, Jun Kwan, Keum Soo Park, Dong Hoon Choi, Yang Soo Jang
Journal: Journal of the American College of Cardiology (2011)
Effects of pulmonary fibrosis on the distribution of edema. Computed tomographic scanning and morphology.
Authors: M P Zwikler, T M Peters, R P Michel
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The pulmonary interstitium acts as an important safety factor against alveolar flooding. To test the hypothesis that in advanced fibrosis, edema is redistributed away from a less compliant interstitium to flood alveoli, we induced severe left lung fibrosis in six dogs with radiation and intratracheal bleomycin. Twenty-four months later, edema was induced by infusing 20% body weight lactated Ringer's solution over 30 min, preceded and followed by computed tomography (CT) scanning. Lower lobes were frozen, and samples were taken for extravascular lung water measurements (Qwl/dQl), regional blood volume, and light microscopic grading of interstitial and alveolar edema. The total volumes of the control and fibrotic lungs were 800 +/- 63 and 45 +/- 10 ml (SE), respectively, indicative of severe fibrosis. Before edema, the fibrotic carinal and basal slices had CT densities 3.5 and 2.2 times greater than respective control slices. After edema, the densities of all control lung slices rose 2.5 times and that of fibrotic carinal and basal slices rose 1.5 times. Edema significantly accentuated the small gravity-dependent gradient in CT density of control lungs, but it had minimal effect on this gradient in fibrotic lungs. The Qwl/dQl for control and fibrotic lower lobes were 8.7 +/- 0.8 and 6.8 +/- 0.7 g H2O/g dry lung, respectively, but the amounts of water per lung volume were similar, and there was no gravity-dependent gradient in Qwl/dQl or in regional blood contents. By light microscopy, we found significantly less interstitial and more alveolar edema in the fibrotic lobes. We conclude that in severe pulmonary fibrosis, similar amounts of water accumulate per lung volume as in controls, and that there is predominant alveolar flooding over interstitial edema. We also conclude that the gravity-dependent gradients in CT densities postedema in the control lungs are not accounted for by edema fluid or congestion, but probably by atelectasis.