tbuckley/cabot-search huggingface dataset:
Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer
Authors: Thomas Stanislawski, Ralf-Holger Voss, Carina Lotz, Elena Sadovnikova, Ralph A. Willemsen, Jürgen Kuball, Thomas Ruppert, Reinder L. H. Bolhuis, Cornelius J. Melief, Christoph Huber, Hans J. Stauss, Matthias Theobald
Journal: Nature Immunology (2001)
Deletion of Crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2
Authors: Toshimitsu Kishimoto, Jelena Radulovic, Marko Radulovic, Chijen R. Lin, Christina Schrick, Farideh Hooshmand, Ola Hermanson, Michael G. Rosenfeld, Joachim Spiess
Journal: Nature Genetics (2000)
Abstract P127: Ayurveda Improves Arterial Stiffness and Cardiometabolic Risk in Coronary Patients: A Prospective Pilot Study
Authors: Robert DuBroff, Vasant Lad, Cristina Murray-Krezan
Journal: Circulation (2014)

Introduction: Ayurveda is the ancient East Indian holistic approach to health that includes yoga, meditation, breathing exercises, medicinal herbs, and other practices. Although it has been practiced for nearly 5000 years there is little objective data regarding its efficacy in coronary disease. Hypothesis: Can the addition of Ayurveda to usual care improve markers and risk factors of cardiovascular disease? Methods: Twenty-six volunteers with a history of prior myocardial infarction, coronary bypass surgery, or coronary angioplasty/stent were recruited from the University of New Mexico cardiology clinics. Each patient underwent consultation with a single Ayurvedic specialist and received personalized instruction in daily yoga, meditation, breathing, medicinal herbs, and a caloric unrestricted Ayurvedic diet. Standardized measurements of arterial stiffness (pulse wave velocity) and cardiometabolic risk factors were obtained at baseline and after 90 days of therapy. Results: Nineteen patients, mean age 71.6 years, completed the study, six dropped out and one was lost to follow up. Among hypertensive patients (n=15), 60% (9 of 15) had either a &gt;10 mm Hg drop in systolic blood pressure (n=4) or required a reduction in anti-hypertensive medications due to persistent systolic blood pressure &lt; 110 mm Hg (n=5). Statistical analysis was performed using the paired student’s t test. Conclusion: This pilot study suggests that short term Ayurvedic therapy improves arterial stiffness and many cardiometabolic risk factors in patients with coronary artery disease. These findings support the need for a randomized controlled trial to further study the effects of Ayurveda on cardiovascular disease.
Phase I accelerated dose-escalating safety and pharmacokinetic (PK) study of aryl-hydrocarbon receptor-mediated aminoflavone prodrug AFP464 in advanced solid tumors.
Authors: C. Massard, C. A. Gomez-Roca, R. Bahleda, B. Nguyen, V. D'hondt, T. Besse-Hammer, A. Awada, J. Soria
Journal: Journal of Clinical Oncology (2010)

2561 Background: AFP464 is a dimethanesulfonate derivative of aminoflavone that has strong anti-tumor activity against a variety of solid tumors through the Aryl hydrocarbon receptor-(AhR) mediated signal transduction. Methods: Patients (pts) with advanced solid tumors refractory to conventional therapy received AFP464 as a 3-hr IV infusion on Days 1 and 8 every 21 days. Cohorts of one patient per dose level were enrolled until a Grade 2 adverse event was observed, after which cohorts of 3-6pts were treated. Ten additional pts were treated at the MTD for pharmacodynamic evaluation. Inclusion criteria included age > 18 yrs, ECOG PS 0-2 and adequate organ functions. Tumor response was assessed by RECIST. Results: 30 heavily pretreated pts (median of 6 prior regimens, range1-14) were enrolled, with a median age of 59 yrs. Seven dose levels from 14 to 103 mg/m2 were evaluated. At 103 mg/m2, 2/3 pts had DLT, one with a G3 decreased DLco and one with bilateral pulmonary infiltrates which resolved with steroid treatment. The MTD and recommended phase II dose was 74 mg/m2 where 1/6 patient had asymptomatic G3 decreased DLco. Across all dose levels, regardless of drug causality, nausea/vomiting (42%) and asthenia (35%) are the most common adverse events, followed by pyrexia (27%), anemia (19%), dyspnea (19%), diarrhea (15%), cough (12%) and fatigue (12%). DLco decreases were observed in 11(37 %, 8 being G2 or 3) of patients across different dose levels. PKs of AF were dose proportional with Cmax at the MTD dose being 30 times the IC90 of sensitive breast cancer cell lines. 9/25 (36%) evaluable pts to date had stable disease of up to 6 cycles (median 4, range 2-6, breast, ovarian, renal, CRC, prostate, thyroid and mesothelioma). Conclusions: AFP464 administration is feasible with minimal bone marrow suppression. The high percentage of stable disease observed in a highly refractory patient population merits further phase II testing. Immunohistochemistry analysis of AhR localization from patients' tumor biopsies is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tigris
Controlled Comparison of Attitudes of Psychiatrists, General Practitioners, Homosexual Doctors and Homosexual Men to Male Homosexuality
Authors: D Bhugra, M King
Journal: Journal of the Royal Society of Medicine (1989)

A controlled analysis of the attitudes of doctors and homosexual men to male homosexuality is reported. Not surprisingly the homosexual men held the most liberal attitudes which served as a yard-stick against which the doctors' attitudes could be assessed. The implications of these data, collected before the AIDS era, are discussed in terms of the current needs of homosexual patients.
Reduced dark-adaptation: an indication of lithium's neuronal action in humans
Authors: H. M. Emrich, J. Zihl, C. Raptis, A. Wendl
Journal: American Journal of Psychiatry (1990)

Although lithium plays a major role in therapy and prophylaxis of affective psychoses, no direct indication of its neuronal action in humans exists. A lithium-induced strong reduction of foveal dark-adaptation was found in healthy volunteers, and a lithium-induced reduction was also measured in patients with affective psychoses. Dark-adaptation measurements apparently offer the opportunity for in vivo monitoring of lithium's CNS effects in humans and may predict lithium's clinical efficacy.
A Bioavailability and Pharmacokinetic Study of Oral and Intravenous Hydroxyurea
Authors: Gladys I. Rodriguez, John G. Kuhn, Geoffrey R. Weiss, Susan G. Hilsenbeck, John R. Eckardt, Allison Thurman, David A. Rinaldi, Stephanie Hodges, Daniel D. Von Hoff, Eric K. Rowinsky
Journal: Blood (1998)
The Problem of Distribution of a Nerve Growth Factor Specific for Spinal and Sympathetic Ganglia
Authors: Elmer D. Bueker, Isaac Schenkein, Joan L. Bane
Journal: Cancer Research (1960)

Enhancement of the nerve growth-promoting factor in mouse sarcomas by their passage as grafts in the chick embryo, as reported in the literature (8, 17), was confirmed with sarcomas MA387 and T241. No evidence for enhancement was observed with normal mouse tissues (Table 1).

Low levels (1–2+) of growth-promoting activity were associated with cell-free derivatives from each of the following mouse tissues: kidney, thymus, spleen, placenta, heart, and voluntary muscles (Tables 2, 3). Lung and liver fractions were negative. The mouse submaxillary gland fractions were the most potent source and confirm the observations reported (4, 7, 12).

Fractions from lumbosacral spinal ganglia, spinal cord, and the eviscerated-decapitated carcass of the 7- to 8-day chick embryo gave indications of having nerve growth-stimulating properties (Tables 2, 3). Similar fractions from the combined axial structures (spinal ganglia, spinal cord, somite derivatives, and notocord) produced maximum (3–4+) outgrowth.

Protein fractions were prepared from mouse submaxillary glands and from axial structures of the 7- to 8-day chick embryo (Table 4). Traces of RNA and no DNA were found in these fractions. No decrease in the activity of the growth factor was observed after incubation with RNase or DNase. From these observations we concluded that the growth factor was associated with the protein component.

No explanation can be offered at this time for the high levels of potency in the mouse submaxillary glands or the localization at lower levels of activity in axial structures of the 7- to 8-day chick embryo (Tables 3, 4). We tentatively submit the hypothesis that nerve growth-stimulating entities are fairly widespread in the tissues. Their succeessful demonstration will depend in each case on the development of adequate techniques.
Inhibition of MAPK signaling cascade in prostate cancer cells by imido-substituted-naphthoquinone analogs
Authors: Robert Copeland, Jharna Das, Oladapo Bakare, YaYin Fang, Desta Beyene, Yasmine Kanaan
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3296 

Prostate cancer (PC) is the most commonly diagnosed cancer in American men with an estimated 218,890 new cases diagnosed in 2007. Androgen ablation is a highly effective palliative therapy; however, most men eventually relapse due to the presence of androgen independent cancer cells. Currently there is no therapy that effectively eliminates these androgen independent PC cells. MAPK pathways play a critical role responsible for survival and proliferation of androgen independent cells. Our hypothesis, that an enhanced response in PC therapy may require inhibitors that affect multiple signal transduction pathways. In our studies, imido-substituted naphthoquinones (ISN) have been synthesized, that are selective inhibitors of MAPK. Experiments with 2-chloro-3-(N-succinimidyl)-1,4-naphthoquinone and analogs have IC50s against purified MEK in the range of 0.4-10 υM. Subsequently these ISN analogs were tested in cell proliferation assays in androgen sensitive (LNCaP, CWR-22) and androgen insensitive (PC-3, DU-145) cells. Growth inhibition of each cell line revealed significant anti-tumor activities within concentration ranges of 1-3 υM. On the basis of this cell-based cytotoxicity screen, 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone (DCDMNQ) demonstrated the highest efficacy. To verify that DCDMNQ maintains ability to inhibit MAP kinases we performed Western blot analysis to evaluate the effect of this compound on generation of phosphorylated MAPK protein in PC-3 and DU-145 cell lines. These results demonstrated that DCDMNQ can inhibit MEK, ERK, AKT and p38 phosphorylation either through inhibition of multiple kinases or via direct inhibition which would then prevent downstream phosphorylation. Active small molecule kinase inhibitors to date are ATP mimics that bind to the intracellular ATP binding domain within the kinase. It has been proposed that MEK1/2 can be inhibited through a novel, noncompetitive mechanism. X-ray crystallography structure of MEK1/2 in complex with MgATP reveals that the enzyme has a unique inhibitor binding pocket adjacent to the ATP binding site. We carried out molecular modeling using DCDMNQ, the published structure of the complex of MEK with MgATP, and the MEK inhibitor, 5-bromo-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-benzamide to explore whether imido-substituted 1,4-naphthoquinones might bind via a similar non-competitive mechanism. Our studies show that in the crystal structure a binding pocket for DCDMNQ is deep inside of MEK. Evaluation of bonding for DCDMNQ when docked to this pocket, demonstrates that it can form hydrogen bonds thereby inducing conformational changes in the unphosphorylated MEK1/2 that locks it into a closed but catalytically inactive species. These ISN compounds, therefore represent a novel class of MAPK inhibitors.    Supported by NCI grant U54-CA914-31 and G12 RR003048 RCMI
An End To Torture: Strategies for its Eradication
Authors: Derek Summerfield
Journal: BMJ (1999)

Ed B Duner St Martin's Press, £15.95, pp 256 ISBN 1 85649 622 8 Rating: ![Graphic][1]</img>![Graphic][2]</img> Torture has a venerable history, documented back to the rule of Ramses II around 1200 BC. In the Middle Ages in Europe it was esteemed as the high road to confessed truth, and even salvation, yet by 1800 judicial codes were casting it as a thing of the past and the last resort of the barbarian. No such fastidiousness attends the present day, with torture used regularly in at least 90 countries. People think of torture as a kind of Gothic horror story, wherein unspeakable things are inflicted in secret dungeons to extract information. This happens, of course, but most … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Personality attributes and affective disorders
Authors: Robert M. Hirschfeld, Gerald L. Klerman
Journal: American Journal of Psychiatry (1979)

To determine the personality characteristics associated with affective disorders the authors administered a battery of self-report personality inventories to a sample of hospitalized affective patients when their manifest symptoms had abated. Patients were instructed to answer according to their premorbid personalities. The personality characteristics assessed in the 73 depressive and 24 manic patients included neuroticism and extraversion from the Maudsley Personality Inventory, obsessional pattern, hysterical pattern, and oral pattern from the Lazare-Klerman-Armor Personality Inventory, obsessional state and trait from the Leyton Obsessionality Inventory, and solidity, stability, and validity from the Marke-Nyman Temperament Survey. Depressive patients demonstrated more neuroticism, introversion, and obsessionality than manic patients or normal individuals. The manic patients differed from normal persons only on obsessionality.
"Atypical" Pneumonia Alert
Authors: Joan Stephenson
Journal: JAMA (2003)

The World Health Organization (WHO) issued a global alert on March 12 about a pneumonia-like illness of unknown origin. As of March 24, 456 suspect and probable cases of severe acute respiratory syndrome (SARS) and 17 deaths had been reported to the WHO (http://www.who.int/csr/sars/en/).
AEROSOL PENICILLIN IN ALLERGIC PATIENTS WITH RESPIRATORY INFECTIONS
Authors: M A GREEN
Journal: Annals of Internal Medicine (1949)

Article1 August 1949AEROSOL PENICILLIN IN ALLERGIC PATIENTS WITH RESPIRATORY INFECTIONSMAYER A. GREEN, M.D., F.A.C.P.MAYER A. GREEN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-31-2-260 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe inhalational administration of antibiotics and chemicals has developed into a practicable and effective approach in the treatment of certain respiratory tract diseases.The advent of penicillin with its unique capacity for nebulization lent impetus to the application of this technic and to the accumulation of scientific data pertaining to the bacteriology and physiology of the respiratory system. The distribution and remarkable absorptive capacity of the respiratory tract mucous membrane provide a wide area for the topical application and absorption of aerosolized penicillin.The clinical application of aerosolized penicillin has been based on certain fundamental and essential observations such as...Bibliography1. BRYSONSONSOMELASKIN : Aerosolization of penicillin solutions, Science, 1944, c, 33. CrossrefGoogle Scholar2. SEGAL MS: Progress in inhalation therapy, Mod. Med., 1946, xiv, 63. Google Scholar3. HUMPHREYJOULES JHH: Penicillin inhalation in pulmonary disease, Lancet, 1946, ii, 221. CrossrefGoogle Scholar4. BARACHGARTHWAITERULE ALBC: The use of penicillin aerosol in broncho-pulmonary and sinus infections, N. Y. State Jr. Med., 1946, xlvi, 1703. Google Scholar5. ABRAMSON HA: Combined penicillin and hydrogen peroxide aerosol therapy in lung infections, Ann. Allergy, 1946, iv, 199. Google Scholar6. Editorial Comment: Jr. Am. Med. Assoc., 1946, cxxxii, 286. Google Scholar7. VERMILYE HN: Aerosol penicillin in general practice, Jr. Am. Med. Assoc., 1945, cxxix, 250. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pittsburgh, Pennsylvania*Received for publication February 24, 1948.†Since this report was originally compiled, approximately 300 aerosol penicillin treatments have been administered to 128 allergic patients. The previous findings have been confirmed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byALLERGY, ANTIBIOTICS AND CHEMOTHERAPEUTICSBisherige Erfahrung mit der Aerosol-Behandlung 1 August 1949Volume 31, Issue 2Page: 260-270KeywordsAntibioticsBacteriologyMucous membranesPenicillinPulmonary diseasesRespiratory physiologyRespiratory systemRespiratory system proceduresUpper respiratory tract infections ePublished: 1 December 2008 Issue Published: 1 August 1949 PDF downloadLoading ...
Abstract P044: Ten-Year Blood Pressure Trajectories and Long-Term Risk of Cardiovascular Mortality: The Minnesota Business and Professional Men Study
Authors: Susanne M Tielemans, Johanna M Geleijnse, Hendriek C Boshuizen, Sabita S Soedamah-Muthu, Alessandro Menotti, David R Jacobs, Henry Blackburn, Daan Kromhout
Journal: Circulation (2014)

Introduction: We characterised 10[[Unable to Display Character: &amp;#8209;]]year trajectories of annual blood pressure (BP) measurements and studied the added value on long-term cardiovascular disease (CVD) mortality in comparison to a single baseline BP measurement. Methods: This study is based on data from 266 men, aged 45 to 55 years, who participated in the Minnesota Business and Professional Men Study. BP was measured annually between 1947[[Unable to Display Character: &amp;#8209;]]1957, a time when only very high levels of BP were treated. Men who did not die before 1957 and did not have a history of myocardial infarction or stroke were included. We identified BP trajectories by means of finite mixture group-based trajectory modelling (PROC TRAJ in SAS). For each individual, time to death was defined as the difference in years between 1957 and year of death (the last man died in 2002). Cox proportional hazards analysis was used to examine BP trajectories in relation to CVD mortality. Results: All 266 men died and 142 (53.4%) from CVD, with mean (± sd) time to death 21±10 years. We identified four systolic BP trajectories with baseline mean systolic BP levels ranging from 112 (SBP1) to 165 (SBP4) mmHg. This difference of 53 mmHg in baseline systolic BP level was associated with a hazard ratio (HR) of 2.4 (95% CI: 1.5-3.8) for CVD mortality. From age 45 to 65, mean systolic BP levels of the four trajectories (Figure 1A) increased from 0.4 to 2.1 mmHg/year for SBP1 to SBP4. For systolic BP trajectories, the HR of CVD mortality increased from 1.6 (SBP2) to 4.2 (SBP4), compared to men in SBP1 (Figure 1A). A similar pattern was observed for diastolic BP (Figure 1B). Conclusion: In this population of middle[[Unable to Display Character: &amp;#8209;]]aged US men, the increase in BP was strongest in those with the highest BP levels. Trajectories of BP predicted CVD mortality much better than a single BP measurement.
Investigations of Substances in Mouse Tissues Inducing Alteration of Normal Host-Homograft Relationships&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;3&lt;/xref&gt;
Authors: Eugene D. Day, Nathan Kaliss, Arthur I. Aronson, Bradley F. Bryant, David Friendly, Frederick C. Gabrielson, Priscilla M. Smith
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Investigations of Substances in Mouse Tissues Inducing Alteration of Normal Host-Homograft Relationships Get access Eugene D. Day, Eugene D. Day Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Nathan Kaliss, Nathan Kaliss Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Arthur I. Aronson, Arthur I. Aronson Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Bradley F. Bryant, Bradley F. Bryant Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar David Friendly, David Friendly Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Frederick C. Gabrielson, Frederick C. Gabrielson Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Priscilla M. Smith Priscilla M. Smith Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 1, August 1954, Pages 145–159, https://doi.org/10.1093/jnci/15.1.145 Published: 01 August 1954 Article history Received: 12 April 1954 Published: 01 August 1954
New Type of Drug for Heart Failure
Authors: Rita Rubin
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 13665: Atrial Fibrillation Patterns in the Community and Risks of Stroke, Heart Failure, or Death
Authors: Steven Lubitz, Carlee Moser, Lisa Sullivan, Michiel Rienstra, João Fontes, Mark Villalon, Manju Pai, Jared Magnani, Xiaoyan Yin, Daniel Levy, Michael Pencina, Martin Larson, Patrick Ellinor, Emelia Benjamin
Journal: Circulation (2011)

Steven Lubitz, 2011 Finalist and Presenting Author
Systematic Reviews: Rationale for systematic reviews
Authors: C D Mulrow
Journal: BMJ (1994)

Systematic literature reviews including meta-analyses are invaluable scientific activities. The rationale for such reviews is well established. Health care providers, researchers, and policy makers are inundated with unmanageable amounts of information; they need systematic reviews to efficiently integrate existing information and provide data for rational decision making. Systematic reviews establish whether scientific findings are consistent and can be generalised across populations, settings, and treatment variations, or whether findings vary significantly by particular subsets. Meta-analyses in particular can increase power and precision of estimates of treatment effects and exposure risks. Finally, explicit methods used in systematic reviews limit bias and, hopefully, will improve reliability and accuracy of conclusions.