tbuckley/cabot-search huggingface dataset:
ERK5 Activation in Macrophages Promotes Efferocytosis and Inhibits Atherosclerosis
Authors: Kyung-Sun Heo, Hannah J. Cushman, Masashi Akaike, Chang-Hoon Woo, Xin Wang, Xing Qiu, Keigi Fujiwara, Jun-ichi Abe
Journal: Circulation (2014)

Efferocytosis is a process by which dead and dying cells are removed by phagocytic cells. Efferocytosis by macrophages is thought to curb the progression of atherosclerosis, but the mechanistic insight of this process is lacking.When macrophages were fed apoptotic cells or treated with pitavastatin in vitro, efferocytosis-related signaling and phagocytic capacity were upregulated in an ERK5 activity-dependent manner. Macrophages isolated from macrophage-specific ERK5-null mice exhibited reduced efferocytosis and levels of gene and protein expression of efferocytosis-related molecules. When these mice were crossed with low-density lipoprotein receptor(-/-) mice and fed a high-cholesterol diet, atherosclerotic plaque formation was accelerated, and the plaques had more advanced and vulnerable morphology.Our results demonstrate that ERK5, which is robustly activated by statins, is a hub molecule that upregulates macrophage efferocytosis, thereby suppressing atherosclerotic plaque formation. Molecules that upregulate ERK5 and its signaling in macrophages may be good drug targets for suppressing cardiovascular diseases.
Abstract 3591: Discovery of SB1317: A novel small molecule macrocycle with a unique kinase inhibitory spectrum in phase 1 clinical trials for hematological malignancies
Authors: Anthony William, Stephanie Blanchard, Angeline Lee, Anders Poulsen, Eric Sun, Ee Ling Teo, Harish Nagaraj, Kay Lin Goh, Wai Chung Ong, Kee Chuan Goh, Mohammed K. Pasha, Ramesh Jayaraman, Jeanette M. Wood, Kantharaj Ethirajulu, Brian W. Dymock
Journal: Cancer Research (2011)

Abstract Introduction: During our quest to find novel kinase inhibitor motifs for our protein kinase research projects we discovered a novel series of macrocyclic structures which possess unique but tunable kinase inhibitory profiles. Here we present the chemical structure of SB1317 and the SAR studies leading to the discovery of this novel CDK/FLT3/JAK2 inhibitor, currently in clinical trials for hematological malignancies. Methods/Results: The unusual structure of SB1317 is characterized by a biaryl connection to the hinge-binding 2-anilinopyrimidine and an allylic tertiary amine – homo allylic ether linker forming an 18-membered macrocyclic ring. Combination of the biaryl motif and unsaturation in the linker confers limited conformational freedom and may explain the specific biological activity observed with this series. Following extensive SAR studies a single preferred compound, SB1317, emerged with potent CDK (IC50 against CDKs 1, 2 and 9 = 9, 5 and 3 nM, respectively), FLT3 (IC50 = 19nM) and JAK2 (IC50 = 19nM) potency. SB1317 has low molecular weight and good physicochemical properties conferring good oral exposure and prompting its further evaluation in vitro and in in vivo cancer models. Following promising efficacy data in these studies, SB1317 was nominated as the preferred candidate for progression to the clinic. SB1317 was synthesized via a ring-closing metathesis (RCM) strategy where the macrocycle was formed from coupling the two halves of the molecule to provide a diene which was then closed by RCM using either Grubbs or Zhan catalysts. Crucially the RCM reaction requires acidic conditions to neutralize the basic centre to allow the metathesis to proceed. Conclusions: SB1317 is a low molecular weight compact macrocyclic structure with a unique spectrum of kinase activity suggesting it may have particular utility in the treatment of hematological malignancies and potential for solid tumor therapy as well. SB1317 is currently being developed in the clinic by Tragara Pharmaceuticals (San Diego, CA) under the name TG02. 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 3591. doi:10.1158/1538-7445.AM2011-3591
Flu vaccine associated with reduced risk of acute myocardial infarction
Authors: N. Hawkes
Journal: BMJ (2013)

Researchers in Australia have found an association between influenza vaccination and the incidence of acute myocardial infarction among hospital patients.

Flu often goes undetected in hospital patients, but the researchers used nose and throat swabs and blood tests to detect recent infection. Their study, published in Heart ,1 found that 12% of patients (34/275) who were treated for acute myocardial infarction over three flu seasons (2008-10) at a Sydney hospital tested positive for previous flu infection, whereas the proportion in a group of control patients who had not had an acute myocardial infarction was just under 7% (19/284) (odds …
Artificially Induced Endometrial Cycles and Establishment of Pregnancies in the Absence of Ovaries
Authors: Daniel Navot, Neri Laufer, Juri Kopolovic, Roni Rabinowitz, Arie Birkenfeld, Aby Lewin, Menachem Granat, Ehud J. Margalioth, Joseph G. Schenker
Journal: New England Journal of Medicine (1986)

In eight women with ovarian failure, we induced histologically normal endometrial function during a preparatory cycle consisting of sequential administration of estrogen and progesterone. During a subsequent cycle, endometrial stimulation was synchronized with surrogate-embryo transfer performed on days 16 to 21. Among the eight women, two pregnancies were established by embryo transfer on days 18 and 19. In both women, ovarian tissue was absent, and these patients therefore serve as an in vivo model for the isolated effects of estrogen and progesterone on implantation and maintenance of pregnancy. Treatment with exogenous estrogen was mandatory up to the 11th week of gestation, and treatment with progesterone until the 18th to 22nd weeks. We conclude that it is biologically feasible to simulate the essential hormonal and endometrial milieu of a fertile menstrual cycle and early gestation solely by the administration of estrogen and progesterone. Days 18 to 19 of the cycle are recommended for successful embryo implantation with this treatment program.
Angiotensin II Receptor Antagonist TCV-116 Reduces Graft Coronary Artery Disease and Preserves Graft Status in a Murine Model
Authors: Yutaka Furukawa, Akira Matsumori, Toshiro Hirozane, Shigetake Sasayama
Journal: Circulation (1996)

Despite the current progress in immunosuppressive regimens, the incidence of graft coronary artery disease (CAD) after cardiac transplantation has not decreased. Recent study has revealed that angiotensin-converting enzyme (ACE) inhibition decreases CAD in rats; however, it is not clear whether this beneficial effect of ACE inhibition is due to a decrease in production of angiotensin II (Ang II) or inhibition of bradykinin degradation. To determine whether Ang II type 1 receptor (AT1-R) blockade has an inhibitory effect on CAD, we evaluated the effects of TCV-116, an AT1-R antagonist, in a murine model of cardiac transplantation.Hearts of DBA/2 mice (H-2d) were transplanted heterotopically to B10.D2 mice (H-2d). Recipients were treated orally with TCV-116 (10 mg/kg per day), captopril (100 mg/kg per day), or vehicle only. Graft status, as assessed by palpation and inspection at laparotomy 70 days after transplantation, was preserved better in the TCV-116-treated group (P < .005) and in the captopril-treated group (P < .05) than in the vehicle-treated group. Intimal area in the graft coronary arterial wall decreased to 31% in the TCV-116-treated group (P < .001 versus vehicle-treated group) and to 34% (P < .005) in the captopril-treated group but was 45% in the vehicle-treated group. Fibrotic lesions of the left ventricle were less prominent in the TCV-116-treated (31%; P < .01 versus vehicle-treated group) and captopril-treated groups (33%; P < .05) than in the vehicle-treated group (54%).These findings show that AT1-R blockade is at least as effective as ACE inhibition in management of chronic allograft rejection and suggest that Ang II may play an important role in chronic allograft rejection.
Chaos in the Hall of Mirrors
Authors: K. T. Weber
Journal: Cardiovascular Research (1995)

Journal Article Chaos in the Hall of Mirrors Get access Karl T. Weber Karl T. Weber Series Editor Karl T. Weber. University of Missouri-Columbia, Division of Cardiology, Room MA432 Medical Sciences Building, Columbia, MO 65212, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 3, September 1995, Pages 336–344, https://doi.org/10.1016/S0008-6363(95)00031-3 Published: 01 September 1995
Protein-Bound Iodine in Patients Receiving Perphenazine
Authors: Jane E. Oltman
Journal: JAMA (1963)

IN A RECENT STUDY,<sup>1</sup>it was reported that 11 of 32 chronically schizophrenic patients (34%) who had been receiving perphenazine over a "considerable period," had an elevated PBI level, ie, over 8.0 μg/100 cc. These patients did not exhibit any evidence of thyrotoxicosis. It was assumed that perphenazine alters the PBI by some unexplained mechanism. The current study was pursued both to confirm these previous findings and to elicit further data in this area. Fifty hospitalized, chronically psychotic individuals (29 males and 21 females) who had been receiving perphenazine for at least 6 months were chosen at random. The only other criterion for inclusion in the study was the absence of administration of any other drug. In the group there were 46 schizophrenic patients, 2 chronically manic, and 2 with psychosis due to mental deficiency. They had received perphenazine for periods ranging from 8 to 50 months. The level
Is Type 2 Diabetes an Operable Intestinal Disease?
Authors: Francesco Rubino
Journal: Diabetes Care (2008)

Type 2 diabetes, which accounts for 90-95% of all cases of diabetes, is a growing epidemic that places a severe burden on health care systems, especially in developing countries. Because of both the scale of the problem and the current epidemic growth of diabetes, it is a priority to find new approaches to better understand and treat this disease. Gastrointestinal surgery may provide new opportunities in the fight against diabetes. Conventional gastrointestinal operations for morbid obesity have been shown to dramatically improve type 2 diabetes, resulting in normal blood glucose and glycosylated hemoglobin levels, with discontinuation of all diabetes-related medications. Return to euglycemia and normal insulin levels are observed within days after surgery, suggesting that weight loss alone cannot entirely explain why surgery improves diabetes. Recent experimental studies point toward the rearrangement of gastrointestinal anatomy as a primary mediator of the surgical control of diabetes, suggesting a role of the small bowel in the pathophysiology of the disease. This article presents available evidence in support of the hypothesis that type 2 diabetes may be an operable disease characterized by a component of intestinal dysfunction.
Evaluation of cardiovascular outcomes among U.S. workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Authors: G M Calvert, D K Wall, M H Sweeney, M A Fingerhut
Journal: Environmental Health Perspectives (1998)

Some animal studies and some human studies suggest that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may be associated with adverse effects on the cardiovascular system. As part of a cross-sectional medical study comparing workers employed 15 years earlier in the manufacture of 2,4,5-trichlorophenol or one of its derivatives at two U.S. chemical plants with an unexposed comparison group, we examined the association between TCDD exposure and various cardiovascular outcomes. A total of 281 workers and 260 unexposed referents participated. The workers had substantial exposure to TCDD, as demonstrated by significantly elevated mean serum TCDD concentration of 220 pg/g of lipid, compared with 7 pg/g of lipid among the referents. No significant association was found between TCDD exposure and any of the cardiovascular outcomes including myocardial infarction, angina, cardiac arrhythmias, hypertension, and abnormal peripheral arterial flow. Although our study had sufficient statistical power to detect an elevated risk for cardiac arrhythmias, hypertension, and abnormal peripheral arterial flow, it had low power (approximately 50%) to detect an elevated risk for myocardial infarction and angina. Our review of the literature suggests that our negative findings are consistent with those from other cross-sectional medical studies. Although several mortality studies of TCDD-exposed cohorts found significantly increased risks for cardiovascular disease mortality, similar increased risks were not observed in other mortality studies. The data available do not provide definitive conclusions but indicate that further examination of the association between TCDD exposure and cardiovascular disease should be pursued.
Obligatory Running and Anorexia Nervosa
Authors: Rebecca Dresser
Journal: JAMA (1985)

<h3>To the Editor.—</h3> In challenging the hypothesis that obligatory running is an analogue of anorexia nervosa, Blumenthal et al<sup>1</sup>commit errors of their own. It is legitimate to point out the speculation and imprecision characterizing the article by Yates et al.<sup>2</sup>Yet the critique by Blumenthal and colleagues fails to appreciate the exploratory nature of the original piece and overinterprets the results of their subsequent empirical study. First, Blumenthal et al examine only one of the variety of proposed analogies between obligatory running and anorexia nervosa. Yates and collegues discussed several possibilities: (1) obligatory runners and anorexic women share certain personality characteristics and extreme concern about body size and shape, (2) obligatory running and anorexia nervosa provide individuals with a sense of control, euphoria, and enhanced self-esteem, (3) obligatory runners and anorexic persons deny physical needs, at times endangering their health and lives, and (4) cultural factors affect
New code requires doctors to disclose all links with drug industry
Authors: C. Dyer
Journal: BMJ (2011)

Doctors who contract after 1 May to act as consultants or advisers to drug companies in the United Kingdom will be obliged to declare the arrangement whenever they write or speak in public on any issue relating to the company, under new industry rules.

From next year companies will also have to disclose the total amounts paid to consultants and the number of recipients, although the consultants will not have to be named.

The rules form part of the 2011 code of practice of the Association of the British Pharmaceutical Industry. Important changes include new rules …
Massive bladder haemorrhage
Authors: J A Murray, N Rooney, F E Preston
Journal: BMJ (1986)

succession of withdrawals of non-steroidal antiinflammatory drugs, including several of the most recently introduced and best tested products.The supporting evidence for withdrawal has not been published, but the decisions seem to have been based on yellow cards or journal anecdotes.Such reports are useful for generating hypotheses about possible risks but are of practical value only when the events reported are very rare or unusual.NHS data cannot be used to provide estimates for the number of patients who might be at risk from adverse reactions.For example, 12 000 pre- scriptions could provide a month's supply for 12 000 patients or a year's supply for 1000.Some of the non-steroidal anti-inflammatory drugs, such as indomethacin, have been used by many patients for up to 20 years, while others, such as piroxicam, have been available for five years or less.The authors cannot distinguish short term from long term use among their patients or distinguish between individuals whose ulcers were caused by non-steroidal anti-inflammatory drugs and those whose ulcers would have occurred spontaneously.They have no estimate of the
Arthritis and You
Authors: Edward F. Rosenberg
Journal: JAMA (1960)

Patients suffering with chronic arthritis often have great curiosity about their ailments. Some read extensively among publications available to laymen. This type of reading may be helpful in that it allays fears and anxieties, leads to a better co-operation between patients and physicians, stimulates a more rational approach to therapy, and assists in the planning of a fuller and more effective life. The result of this type of reading, however, is not always beneficial. Material presented for reading by sufferers of chronic arthritis has often been prepared with baser aims. False, misleading, dramatic, and grossly inaccurate material has often been presented in publications intended for this purpose. Many patients have lost valuable time and have perhaps suffered irretrievable damage to important structures following a will-of-the-wisp treatment program directed in this type of literature on the subject of arthritis. This new volume, intended for laymen, should be decidedly helpful to the
Peripheral Airway Obstruction
Authors: E. R. McFadden
Journal: JAMA (1976)

IN RECENT years, great progress has been made in our understanding of the chronic obstructive pulmonary syndromes. It now appears that these diseases begin in the periphery of the lung and interfere with the function of the small airways located there long before they produce diagnostically interpretable symptoms or compromise results of the standard tests of lung function, such as one-second forced expiratory volume (FEV<sub>1</sub>) or even more sophisticated measurements, such as airway resistance. Thus, diseases of the peripheral airways may be the earliest lesion in the pathogenetic course of chronic obstructive lung disease, and more important, at this stage the abnormalities may be reversible.<sup>1-3</sup>Consequently, the concept of small-airway disease has become quite important and has proved useful in helping to explain uncommon, perplexing clinical syndromes such as disproportionately severe hypoxemia in obstructive disease associated with only a modest overall increase in flow resistance. Yet, this area of
Imidazoles, Ketoconazole, Amphotericin B, and Candida guilliermondii
Authors: GARY WILSON
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 June 1985Imidazoles, Ketoconazole, Amphotericin B, and Candida guilliermondiiGARY WILSON, M.D., JAMES E. PEACOCK JR., M.D.GARY WILSON, M.D.Search for more papers by this author, JAMES E. PEACOCK JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-6-866_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The case of amphotericin-B-resistant Candida guilliermondii described by Dick and colleagues (1) certainly epitomizes the growing problem of fungal disease and its therapy in the immunocompromised patient. However, the report also left several questions unanswered.One question relates to the effect of prior imidazole exposure on fungal sensitivity to amphotericin B. The antifungal activity of amphotericin B is mediated through binding of the drug to ergosterol within fungal cell walls (2). In contrast, imidazoles inhibit ergosterol synthesis. Thus, exposure to imidazoles may result in the development of progressive resistance to amphotericin B because of decreasing ergosterol content...References1. DICKROSENGARDMERZSTUARTHUTCHINSSARAL JBWRGR. Fatal disseminated candidiasis due to amphotericin-B-resistant Candida guilliermondii. Ann Intern Med. 1985;102:67-8. LinkGoogle Scholar2. MEDOFFKOBAYASHI GG. Strategies in the treatment of systemic fungal infections. N Engl J Med. 1980;302:145-55. CrossrefMedlineGoogle Scholar3. COSGROVEBEEZERMILES RAR. In vitro studies of amphotericin B in combination with the imidazole antifungal compounds clotrimazole and miconazole. J Infect Dis. 1978;138:681-5. CrossrefMedlineGoogle Scholar4. SUTHERLANDROLINSON RG. Characteristics of methicillin-resistant staphylococci. J Bacteriol 1964;87:887-99. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bowman Gray School of Medicine of Wake Forest University Winston-Salem, NC 27103 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPathophysiology of Heart FailureClinical assessment and investigation of patients with suspected heart failureAgents for treatment of invasive fungal infectionsPrevention of fungal sepsis in patients with prolonged neutropenia: A randomized, double-blind, placebo-controlled trial of intravenous miconazole 1 June 1985Volume 102, Issue 6Page: 866-866KeywordsAmphotericinAntifungalsCandidaCell wallsDrugsFungal diseasesImidazole Issue Published: 1 June 1985 PDF DownloadLoading ...
Co-existence of chronic actinic dermatitis and solar urticaria in three patients
Authors: P.E. Beattie, R.S. Dawe, S.H. Ibbotson, J. Ferguson
Journal: British Journal of Dermatology (2004)

Journal Article Co‐existence of chronic actinic dermatitis and solar urticaria in three patients Get access P.E. Beattie, P.E. Beattie Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: paula_e_beattie@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar R.S. Dawe, R.S. Dawe Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: paula_e_beattie@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar S.H. Ibbotson, S.H. Ibbotson Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: paula_e_beattie@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar J. Ferguson J. Ferguson Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: paula_e_beattie@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 2, 1 August 2004, Pages 513–515, https://doi.org/10.1111/j.1365-2133.2004.06097.x Published: 01 August 2004
Blood CD34−c-Kit+ cell rate correlates with aggressive forms of systemic mastocytosis and behaves like a mast cell precursor
Authors: Sophie Georgin-Lavialle, Ludovic Lhermitte, Cédric Baude, Stéphane Barete, Julie Bruneau, Jean-Marie Launay, Marie-Olivia Chandesris, Katia Hanssens, Christian de Gennes, Gandhi Damaj, Fanny Lanternier, Mohamed Hamidou, Olivier Lortholary, Patrice Dubreuil, Frédéric Feger, Yves Lepelletier, Olivier Hermine
Journal: Blood (2011)
The Generalist Function in Medicine
Authors: Edmund D. Pellegrino
Journal: JAMA (1966)

I am sincerely grateful for the privilege of presenting the first annual American Academy of General Practice (AAGP) lecture and of expressing my convictions on the matter of general medicine— a matter of increasing moment for profession and public alike. I am of the firm conviction that the generalist function is an urgent need of present and future society. I am genuinely concerned about its gradual attenuation even in such broad fields as medicine and pediatrics, and I am convinced that for its refurbishment it must be firmly based in the medical school and the university. We have here one of a growing number of issues in which medical schools and practitioners must confront a public need cooperatively, if they are to meet current social responsibilities. There is much public anxiety that the maximum of new knowledge is not now easily available to all in their own communities. This anxiety