tbuckley/cabot-search huggingface dataset:
Different activation of the endothelial L-arginine and cyclooxygenase pathway in the human internal mammary artery and saphenous vein.
Authors: Z H Yang, L von Segesser, E Bauer, P Stulz, M Turina, T F Lüscher
Journal: Circulation Research (1991)

The endothelium releases substances controlling vascular tone and platelet function. We investigated mediators of endothelium-dependent responses in human internal mammary arteries and saphenous veins. The inhibitor of nitric oxide formation, NG-monomethyl L-arginine, enhanced the sensitivity to norepinephrine (fivefold) and evoked more pronounced endothelium-dependent contractions in internal mammary arteries (19 +/- 6% of 100 mM KCl) than in saphenous veins (2 +/- 1%; p less than 0.005). In internal mammary arteries, NG-monomethyl L-arginine, but not indomethacin, markedly reduced endothelium-dependent relaxations to acetylcholine (from 95 +/- 2% to 39 +/- 7%; p less than 0.005) and prevented those to histamine (78 +/- 6% to 4 +/- 3%; p less than 0.005). In saphenous veins, endothelium-dependent relaxations to acetylcholine were weak (24 +/- 11%), while nitric oxide caused comparable relaxations (85 +/- 3%) as in internal mammary arteries (80 +/- 5%; NS). NG-Monomethyl L-arginine prevented the relaxations to acetylcholine and unmasked endothelium-dependent contractions (30 +/- 10%). Indomethacin and the thromboxane synthetase inhibitor CGS-13080 augmented relaxations of saphenous veins to acetylcholine from 24 +/- 11% to 46 +/- 9% (p less than 0.05). Histamine-evoked contractions were converted to endothelium-dependent relaxations by indomethacin and the thromboxane A2/endoperoxide receptor antagonist SQ-30741 (38 +/- 3% and 40 +/- 6%; p less than 0.05) but not CGS-13080. Thus, 1) nitric oxide mediates endothelium-dependent relaxations in human arteries and veins; 2) internal mammary arteries release more nitric oxide than do saphenous veins, and 3) in saphenous veins, the effects of nitric oxide are reduced by endothelium-derived contracting factors originating from the cyclooxygenase pathway.
Abstract 5430: Frizzled-1 receptor, a potential therapeutic target for atypical teratoid rhabdoid tumor
Authors: Madhavi Chakravadhanula, Victor Ozols, Chris Hampton, Ratan Bhardwaj
Journal: Cancer Research (2014)

Abstract Atypical Teratoid Rhabdoid Tumors (ATRTs) are aggressive tumor types in the field of pediatric neuro-oncology that need new therapeutic strategies since they are associated with significantly worse overall prognosis than other pediatric tumors. A characteristic feature of ATRTs is usually an aberration of SMARCB1/INI1/hSNF5 gene. One of the important developmental pathways for cellular development is the Wnt pathway. Wnt proteins are a family of 19 secreted glycoproteins and act as ligands that bind transmembrane receptors such as the Frizzled receptors. There are 10 known Frizzled receptors, and the binding of a specific Wnt ligand to a specific Frizzled receptor plays a crucial role in the regulation of diverse cellular processes. Perturbation of the activities of Wnt ligands can result in defects in embryonic development and diseased states such as cancer. In our preliminary transcriptome analyses results, Wnt5b and Frizzled-1 receptor (Fz-1) were significantly upregulated in 20 ATRT samples and 3 ATRT cell lines. The binding of Wnt5b with Fz-1 was further confirmed by immunoprecipitation and Western blotting analyses. Treatment of ATRT cells with Fz-1 specific siRNA did not indicate a significant decrease in cell viability. Similarly treatment of ATRT cells with a Fz-1 specific monoclonal antibody (Fz-1Mab) also did not indicate significant decrease in cell viability. However, in this study treatment of cells with a combination of Fz-1 specific siRNA and Fz-1Mab indicated a significant decrease in cell viability. A dose response analysis was performed over time to test various doses of Fz-1Mab with constant Fz-1 siRNA concentrations; a cell titre glo assay was then performed to assess cell viability. The physiologically relevant Fz-1Mab dose was then used to assess the effects of using this combination treatment on Fz-1 and Wnt5b protein levels. A decrease in Fz-1 and Wnt5b protein levels when Fz-1 receptor is blocked by siRNA and Mab indicates that Wnt5b bound to Fz-1 receptor plays an important role in ATRT disease etiology and could be a therapeutic target. Citation Format: Madhavi Chakravadhanula, Victor Ozols, Chris Hampton, Ratan Bhardwaj. Frizzled-1 receptor, a potential therapeutic target for atypical teratoid rhabdoid tumor. [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 5430. doi:10.1158/1538-7445.AM2014-5430
Abstract 4627: Generation and characterization of non-competitive furin-inhibiting nanobodies
Authors: Jeroen Declercq, Jingjing Zhu, Iris Lindberg, Gholamreza H. Ghassabeh, Sandra Meulemans, Alphons J.M. Vermorken, Wim J.M. Van de Ven, Serge Muyldermans, John W.M. Creemers
Journal: Cancer Research (2012)

Abstract Furin belongs to a family of seven closely related subtilisin-like serine endoproteases, known as proprotein convertases (PCs), PC1/3, PC2, PC4, PC5/6, PACE4 and PC7. The physiological role of furin is to cleave and hence activate a large variety of proproteins. Therefore, it is not surprising that it plays a major role in many pathologies such as cancer and infectious diseases. Furin inhibition might be a good strategy for therapeutic intervention, and several furin inhibitors have been generated, although thus far none are entirely furin-specific. To reduce potential side effects caused by cross-reactivity with other proteases, dromedary heavy chain antibodies against catalytically active furin were developed as specific furin inhibitors. Nanobodies derived from these antibodies bind only to mouse and human furin but not to other PCs. In addition, upon overexpression in cell lines, these nanobodies can inhibit the cleavage of three different furin substrates, TGFβ, BAFF and GPC3. The purified nanobodies can also inhibit the cleavage of diphtheria toxin into its enzymatically active A fragment, but do not inhibit cleavage of a small synthetic peptide-based substrate, suggesting a mode of action based on steric hindrance. The inhibitory constant of the purified nanobodies was shown to be in the micromolar range and the nanobodies are non-competitive inhibitors as demonstrated by Dixon plot. Furthermore, anti-furin nanobodies can protect HEK293T cells from diphtheria toxin-induced cytotoxicity as efficiently as the well characterized PC inhibitor nona-D-arginine. In conclusion, these antibody-based single-chain nanobodies represent the first generation of highly specific, non-competitive furin inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4627. doi:1538-7445.AM2012-4627
A Prospective Study of Family History and the Risk of Colorectal Cancer
Authors: Charles S. Fuchs, Edward L. Giovannucci, Graham A. Colditz, David J. Hunter, Frank E. Speizer, Walter C. Willett
Journal: New England Journal of Medicine (1994)

A family history of colorectal cancer is recognized as a risk factor for the disease. However, as a result of the retrospective design of prior studies, the strength of this association is uncertain, particularly as it is influenced by characteristics of the person at risk and the affected family members.
Radiation-associated choroidal neovasculopathy
Authors: Richard F Spaide, Anita Leys, Barbara Herrmann-Delemazure, Peter Stalmans, Michael Tittl, Lawrence A Yannuzzi, Katherine M Burke, Yale L Fisher, K.Bailey Freund, David R Guyer, Jason S Slakter, John A Sorenson
Journal: Ophthalmology (1999)
TCT-151 Eptifibatide and Abciximab are associated with similar outcomes when used during Primary Percutaneous Coronary Intervention for ST-elevation myocardial infarction
Authors: Nicola Ding, Daniel A. Jones, Mark Peterzan, Sean Gallagher, Sotiris Antoniou, Paul Wright, Krishnaraj Rathod, Ajay Jain, Charles Knight, Anthony Mathur, Roshan Weerackody, Andrew Wragg
Journal: Journal of the American College of Cardiology (2013)
Holding smokers accountable for heart disease costs.
Authors: W H Kaesemeyer
Journal: Circulation (1994)

This article discusses escalating health care costs in terms of their principal component, cardiovascular diseases. The role of cigarette smoking is highlighted throughout. A Smoker's Accountability Trust is proposed for the prevention of nonfatal myocardial infarction. It is demonstrated that this approach can contain costs by controlling the root causes of their acceleration.
Pulmonary circulation of the llama at high and low altitudes.
Authors: P Harris, D Heath, P Smith, D R Williams, A Ramirez, H Kruger, D M Jones
Journal: Thorax (1982)

We have studied the pulmonary circulation of three closely related animals, the llama, alpaca, and guanaco. The mean pulmonary arterial pressure of 12 llamas and one alpaca indigenous to high altitude in the Andes was found to be slightly but significantly higher than that of three llamas and three guanacos born and bred at low altitude in England. On the other hand, the medial thickness of the muscular pulmonary arteries and the relative weights of the two ventricles were the same in three llamas and one alpaca at high altitude as they were in one llama and two guanacos at low altitude. It is concluded that the pulmonary vasoconstrictive response to hypoxia, while present, is greatly reduced in this species and it is suggested that this may have taken place by evolutionary adaptation.
Temporary Use of the Jarvik-7 Total Artificial Heart before Transplantation
Authors: Bartley P. Griffith, Robert L. Hardesty, Robert L. Kormos, Alfredo Trento, Harvey S. Borovetz, Mark E. Thompson, Henry T. Bahnson
Journal: New England Journal of Medicine (1987)

Between October 24, 1985, and July 31, 1986, the Jarvik-7 total artificial heart was implanted into six moribund patients in an attempt to test its potential as a bridge from almost certain death to cardiac transplantation. Four of these patients are now well and at home after implantation of the device and subsequent cardiac transplantation. Before transplantation, one patient died with sepsis and multiorgan failure that preceded implantation of the artificial heart. Another patient died with acute rejection 60 days after cardiac transplantation. Fifty-two days of total mechanical support with the artificial heart were accumulated in these six patients, and although the device worked flawlessly and no clinically apparent thromboembolic events occurred, each artificial heart contained areas of macroscopic aggregations of platelets and thrombi. The results of this trial indicate that in properly selected cases, direct benefit to the patient can be obtained when the Jarvik-7 artificial heart is used as a bridge to transplantation.
Autoimmune progesterone dermatitis with persistent amenorrhoea
Authors: I. KATAYAMA, K. NISHIOKA
Journal: British Journal of Dermatology (1985)

Journal Article Autoimmune progesterone dermatitis with persistent amenorrhoea Get access I. KATAYAMA, I. KATAYAMA Department of Dermatology, Osaka University School of Medicine, 1‐1‐50 Fukushima, Fukushima‐ku, Osaka, Japan Search for other works by this author on: Oxford Academic Google Scholar K. NISHIOKA K. NISHIOKA Department of Dermatology, Osaka University School of Medicine, 1‐1‐50 Fukushima, Fukushima‐ku, Osaka, Japan K. Nishioka, Department of Dermatology, Osaka University School of Medicine, Fukushima, Fukushima‐ku, Osaka, Japan. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 112, Issue 4, 1 April 1985, Pages 487–491, https://doi.org/10.1111/j.1365-2133.1985.tb02325.x Published: 01 April 1985 Article history Accepted: 06 September 1984 Published: 01 April 1985
Poor staging and treatment are likely to be behind low bowel cancer survival in UK
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Lower survival among people with bowel cancer in the United Kingdom than among those in similar countries is likely to be because of poor staging and unequal access to the best treatment, new findings indicate.

A study led by the London School of Hygiene and Tropical Medicine was carried out in Australia, Canada, Denmark, Norway, Sweden, and the UK for the International Cancer Benchmarking Partnership. It included more than 310 000 patients whose bowel cancer was diagnosed between 2000 and 2007.

The researchers used population based cancer registries to examine how far the patients’ cancer had spread at the time of diagnosis and to look at the proportion …
Red Cross ensures health of hostages in Peru
Authors: J. Hamilton
Journal: BMJ (1997)

For nearly 80 days 72 hostages have been caught up in a life or death political contest between the Peruvian government and the leftist Tupac Amaru Revolutionary Movement. The survival and good health of the diplomats and government officials from various countries is largely due to efforts by the International Committee of the Red Cross.

The Tupac Amaru Revolutionary Movement seized the Japanese ambassador's residence in Lima, Peru, on …
Abstract 2928: Interleukin-1 receptor-associated kinase-2 (IRAK2) is a critical mediator of endoplasmic reticulum (ER) stress.
Authors: Ravanan Palaniyandi, Samir Benosman, Ying-Chen Hou, Ricardo G. Correa, Minjia Yu, Muhammet Fatih Gulen, Xiaoxia Li, James Thomas, Yasuko Matsuzawa, Shu-Ichi Matsuzawa, John C. Reed
Journal: Cancer Research (2013)

Abstract Endoplasmic reticulum (ER) stress occurs when unfolded proteins accumulate in the lumen of the organelle, triggering signal transduction events that contribute either to cellular adaptation and recovery or alternatively to cellular dysfunction and death. ER stress has been implicated in numerous diseases, including cancer where harsh tumor microenvironments induce ER stress and create pressure for evolution of malignant clones that have acquired mechanisms for successful adaptation to stressful environments. To identify novel modulators of ER stress, we undertook a siRNA library screen of the kinome, revealing Interleukin-1 Receptor-Associated Kinase-2 (IRAK2) as a contributor to unfolded protein response (UPR) signaling and ER stress-induced cell death. Knocking down expression of IRAK2 (but not IRAK1) in cultured mammalian cells suppresses ER stress-induced expression of the pro-apoptotic transcription factor CHOP and activation of stress kinases. Similarly, RNAi-mediated silencing of the IRAK family member Tube (but not Pelle) suppresses activation of stress kinase signaling induced by ER stress in Drosophila cells. The action of IRAK2 maps to the IRE1 pathway, rather than the PERK or ATF6 components of the UPR. Interestingly, ER stress also induces IRAK2 gene expression in an IRE1/XBP1-dependent manner, suggesting a mutually supporting amplification loop involving IRAK2 and IRE1. In vivo, ER stress induces Irak2 expression in mice. Moreover, Irak2 gene knockout mice display defects in ER stress-induced CHOP expression and IRE1 pathway signaling. These findings demonstrate an unexpected linkage of the innate immunity machinery to UPR signaling, revealing IRAK2 as a novel amplifier of the IRE1 pathway involved in ER stress signaling. Future analysis of the role of IRAK2 in animal models of cancer will aid in assessing whether IRAK2 provides a novel targets for potential cancer therapeutics development. (Supported by NIH grant AG-15393). Citation Format: Ravanan Palaniyandi, Samir Benosman, Ying-Chen Hou, Ricardo G. Correa, Minjia Yu, Muhammet Fatih Gulen, Xiaoxia Li, James Thomas, Yasuko Matsuzawa, Shu-Ichi Matsuzawa, John C. Reed. Interleukin-1 receptor-associated kinase-2 (IRAK2) is a critical mediator of endoplasmic reticulum (ER) stress. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2928. doi:10.1158/1538-7445.AM2013-2928 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Neisseria catarrhalis Bacteremia With Meningitis
Authors: Lois E. Pfister
Journal: JAMA (1965)

<i>NEISSERIA GONORRHOEAE</i>and<i>N meningitidis</i>have a well-established pattern of pathogenicity in man. Aerobic nonpathogenic neisseriae, on the other hand, are found normally in the nasopharynx and in the upper respiratory tract. The following report describes a case in which, despite a clinical picture of meningococcemia, a culture of<i>N catarrhalis</i>was developed from blood, spinal-fluid, and throat specimens. <h3>Report of a Case</h3> A 2 1/2-year-old boy was brought to the hospital 18 hours after he developed lethargy, fever, and anorexia, and four hours after petechiae were first noticed on his arms. The physician who saw him did not institute therapy but referred him for immediate admission. The patient's history included persistent rhinorrhea and sore throat during the previous winter. He had also experienced frequent earaches, but not within the six months previous to admission. The patient weighed 28.6 lb (13 kg). He was comatose and had a rectal temperature
Abstract 614: Efficacy of metformin in two mouse models of Li-Fraumeni syndrome
Authors: Ajaikumar B. Kunnumakkara, Regan M. Memmott, Colleen R. Maier, Shigeru Kawabata, Brendan Quinn, Joell Gills, Matthew Dallos, Christine M. Hollander, Phillip A. Dennis
Journal: Cancer Research (2011)

Abstract Li-Fraumeni Syndrome (LFS) is a rare autosomal hereditary disorder that is commonly associated with germline mutations in the TP53 gene. People with LFS are at high risk to develop a wide range of malignancies including breast cancer, brain tumors, acute leukemias, soft tissue sarcomas, bone sarcomas, and adrenal cortical carcinomas. Although no therapies are approved to treat or prevent LFS, preclinical studies have shown that the anti-diabetic drug metformin is preferentially cytotoxic to p53 null cells in the absence of glucose. This led us to hypothesize that metformin has therapeutic potential in LFS. To confirm the p53 dependence of metformin in vitro, isogenic human and murine cancer cell lines were treated with metformin in the absence or presence of glucose. Metformin induced greater toxicity in p53-deficient cells in a dose-dependent manner. Metformin was then tested in two mouse models that recapitulate the increased tumorigenesis and cancer-related mortality in LFS (p53 mutant mice (p53R172H/+) and p53 null mice (p53-/-)). When administered at 5 mg/ml in drinking water, metformin reached steady state plasma concentrations similar to those in diabetic humans. Biomarker studies showed that oral administration of metformin activated AMPK and inhibited the mTOR pathway in liver tissues. To determine the effects of metformin on overall survival, two sets of studies were performed. For each model, treatment with metformin was begun either late in life (for p53R172H/+, 12 mo; for p53-/-, 4 mo) or early in life (for p53R172H/+, 4 mo; for p53-/-, 1 mo). Mice were treated until death. Long-term oral administration of metformin did not cause weight loss or other discernible toxicity. In the late treatment study, metformin significantly prolonged median survival (for p53R172H/+ mice, 20.6 mo vs. 15.8 mo; p=0.0004)(for p53-/- mice, 9.1 mo vs. 5.3 mo; p=0.0006). Likewise, early treatment with metformin also prolonged median survival (for p53R172H/+ mice, median survival 20.5 compared to 13 months; p=0.0025). The early study with p53-/- mice is ongoing, but median survival is undefined in metformin group, compared to 3.6 mo in control group, p=0.0387). These studies show that metformin is well tolerated and highly effective when given early or late in the life span of two mouse models of LFS. Given that metformin is an inexpensive oral drug that is FDA approved, a pilot clinical trial in LFS is planned. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 614. doi:10.1158/1538-7445.AM2011-614
A case of myocarditis associated with IDDM
Authors: T. Mokuno, Y. Sawai, N. Oda, T. Mano, N. Hayakawa, R. Kato, Y. Itoh, K. Shimazaki, M. Kotake, A. Nakai, S. Hiramitsu, M. Itoh, S. Morimoto, A. Nagasaka
Journal: Diabetes Care (1996)

We report a case of diabetic ketoacidosis (DKA) complicated by acute myocarditis, which was confirmed by cardiac biopsy. A 26-year-old man was hospitalized with severe DKA. On admission, nonspecific ST-T change was noted on the electrocardiogram (ECG). The patient's levels of creatine phosphokinase (CPK) and glutamic oxaloacetic transaminase were slightly elevated, but he did not complain of chest discomfort or symptoms of heart disease. On the first day after admission, ST-T elevation was noted on ECG during treatment of DKA. By cardiac angiography and cardiac biopsy, coronary heart disease was ruled out and postmyocarditic change was histologically confirmed. An episode of upper respiratory viral infection before the onset of acute diabetes suggested that the patient suffered from viral-induced myocarditis and consequent development of IDDM. This possibility was confirmed by the clinical course of ECG change, with elevated CPK and lactate dehydrogenase and a slightly elevated antibody titer for echovirus.
ROYAL INFIRMARY FOR DISEASES OF THE CHEST: CASE OF COMPLEX DISEASE OF THE HEART: WITH REMARKS
Authors: R. H. Powell
Journal: BMJ (1856)

had also paralysi of the sixth nerve, as he had no power of abducting the eye: also of the sentient portion of the fifth, as he had no feeling on placing the finger over the coruea, -r around the eye and cheek; probably of the third and fourth cerebral nerves, as the globe was nearly or quite motionless, with inactive iris; the second nerve, also, was paralysed, as the eye was amaurotic, in addition to a dull yellow lens.The left eye, as to sight and movements, seemed pretty good.The result is unknown.CASE iv.This case, in which a fatal termination oc- curred, afforded an opportunity of examining and judging as to the morbid causes of the affection.