tbuckley/cabot-search huggingface dataset:
Abstract 5154: Serotonin signaling as a novel target of tumor angiogenesis
Authors: Ali Zamani, Ling Zhai, Anshu M. Roy, Rongbao Li, Zhican Qu, Yulia Y. Maxuitenko
Journal: Cancer Research (2011)

Abstract Angiogenesis is a well-controlled process that is regulated by multiple factors that are secreted by the cancer cells as well as other cells within the tumor microenvironment. Angiogenesis inhibitors are showing therapeutic efficacy in an increasing number of human cancers. However, in both preclinical and clinical settings, the benefits are transitory and are followed by resistance and a restoration of tumor growth and progression. Therefore, novel anti-angiogenic strategies with complementary mechanisms are needed to maximize efficacy and minimize resistance to current angiogenesis inhibitors. Activation of platelets and blood coagulation frequently occurs in cancer patients. Apart from VEGF, platelets contain several other angiogenic growth factors and inhibitors that are released upon activation and promote tumor neoangiogenesis. Although considerable attention has been focused on platelet peptide growth factors, little is known about the mitogenic effects of nonpeptide platelet products such s serotonin (5-HT), considering that 99% of 5-HT in blood is found in platelets and is released at blood clotting sites. In previous studies, we have shown that endothelial cells express 5-HT receptors and 5-HT has growth stimulatory effcts on multiple types of endothelial cells. We have also demonstrated that 5-HT binds to inhibitory type of G-protein coupled receptors and stimulates the phosphorylation of PYK2/PI3K/AKT/mTOR signaling pathway, the same signaling pathway, which has been activated by most angiogenic factors, including VEGF. In our recent studies, we explored angiogenic promoting activity of 5-HT in the mouse matrigel plug assay (in vivo angiogenesis model system) and antiangiogenic potential of antagonists against 5-HT receptors in xenograft-CAM assay (ex vivo tumor angiogenesis model system). The most importantly, an antagonist against a specific 5-HT receptor demonstrated the synergistic effect in blocking tumor-induced new blood vessel formation when it was applied in combination with Sutent, a FDA approved antiangiogenic drug against VEGF receptor. The results of this study suggest that 5-HT signaling pathway constitute a novel target of tumor angiogenesis in anticancer therapeutic development. 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 5154. doi:10.1158/1538-7445.AM2011-5154
Colonic Crohn's disease and use of oral contraception.
Authors: J M Rhodes, R Cockel, R N Allan, P C Hawker, J Dawson, E Elias
Journal: BMJ (1984)

The prevalence of use of oral contraception before the onset of disease was established in 100 consecutive women attending follow up clinics for inflammatory bowel disease. A significant excess of women with Crohn's disease confined to the colon had taken oral contraceptives in the year before developing symptoms (10/16 (63%] compared with women with small-intestinal Crohn's disease (12/49 (24%); p less than 0.02) and women with ulcerative colitis (3/35 (9%); p less than 0.0005). When the patient groups were matched for age and year of onset of disease usage of oral contraception before the onset of disease was still more common among women with isolated colonic Crohn's disease (9/12, 75%) than among those with ulcerative colitis (2/12 (17%); p less than 0.02) and was also more common than would be expected from reported figures for oral contraception in England and Wales (31.4% of women aged under 41; p less than 0.005). A survey of current patient records showed that isolated colonic disease was at least twice as common among women with Crohn's disease (63/218, 29%) compared with men (25/181, 14%; p less than 0.001). These data support the suggestion made previously that oral contraceptives may predispose to a colitis that resembles colonic Crohn's disease.
Abstract 95: Phylogenetic classification, structural evolution, and functional divergence of the ABC-type transporters: Inferences derived from CDTree/Cn3D software applications
Authors: James S. Song, Myra K. Derbyshire, Fu Lu, John D. Jackson, Roxanne A. Yamashita, Aron Marchler-Bauer, Stephen H. Bryant
Journal: Cancer Research (2010)

Abstract The NCBI's Conserved Domain Database (CDD; http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml), is a collection of annotated multiple sequence alignment models representing ancient conserved protein domains, basic units of protein function and protein evolution. Domain models are annotated with functional sites and can be viewed as sequence alignments together with corresponding 3D structure using the CDTree/Cn3D software applications. CDTree/Cn3D is a domain hierarchy editor which lets the user view and examine conserved domain hierarchies interactively and in great detail. A domain hierarchy is a structured collection of domain models reflecting the domain family's molecular evolution. Here we present our current, functionally annotated evolutionary classifications of the nucleotide-binding domain, transmembrane domain, and periplasmic binding proteins of the ABC (ATP binding cassette)-type transport systems which are involved in the transport of a wide variety of substrates such as sugars, ions, peptides, and more complex organic molecules across membranes. Mutations in ABC transporters cause or contribute to multi-drug resistance, cystic fibrosis, and a range of other human diseases. Using CDTree/Cn3D functionality, subfamilies present in diverse organisms were inferred from the multiple sequence alignments, phylogenetic trees, and the domain architectures of the proteins involved. Furthermore subfamilies, some of which are only comprised of uncharacterized proteins, were annotated with molecular and cellular function and the location of conserved sites, as available in the literature and evident from protein 3D structure. We demonstrate the utility of CDTree/Cn3D in studying the molecular evolution of protein and domain families, and in accelerating the discovery of orthologous groups. CDTree/Cn3D are freely available for download via the CDD website. A version of CDTree, which supports both Mac OSX and Windows operating systems, has recently been made available. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 95.
An improved rabbit ear model for assessing comedogenic substances
Authors: A.M. KLIGMAN, TILLIE KWONG
Journal: British Journal of Dermatology (1979)

A simplified comedogenic assay is described in which test materials are applied for 2 weeks to the ears of rabbits just external to the ear canal. Excised tissue is thus immersed in water at 60°C for 2 min, yielding a sheet of epidermis with microcomedones attached. The magnitude of follicular hyperkeratosis is extracted with the stereomicroscope. Sixteen materials were evaluated by the new and old model which required histological sectioning. Agreement was excellent.
Is it harmful to lower HDL levels?
Authors: John Henahan
Journal: JAMA (1981)

A reduction in the expected number of "coronary events" among patients at high risk for heart disease is ascribed to the drug probucol, according to a Finnish study presented at a recent international conference on lipoproteins and coronary atherosclerosis in Lugano, Switzerland. Since the agent also lowered the patients' high-density lipoprotein (HDL)-cholesterol levels, the findings question the growing belief that high levels of HDL may protect against heart disease. In the five-year study, the incidence of sudden death and fatal and nonfatal myocardial infarction among 184 persons who took probucol in conjunction with a low-cholesterol diet was calculated as 9 per 1,000 per five years, said Dr Tatu Miettinen of the Second Department of Medicine, University of Helsinki. According to a risk index calculated on the basis of initial cholesterol levels, age, weight, blood pressure, and other factors, the expected coronary incidence in this group would have been 18±15 per
Views of Medical Education and Medical Care
Authors: P. C. Anderson
Journal: JAMA (1968)

These seven enjoyable essays are from the outraged school of literature about medical education. It is a scholarly kind of outrage which may come from a painful doubleawareness—first, that medical education has failed to cope with important and proper new responsibilities, and second, that educators can not find a workable plan for catching up. Numerous books and articles and an incredible number of meetings, conferences, retreats, seminars, and workshops represent the views of the outrage school, but none better than this book.  A Massachusetts Institute of Technology physicist views medical education with accuracy and wit; a pediatrician adds a well-written criticism from the behavioral sciences. Dr. John Millis, of Western Reserve, known for the report on Graduate Medical Education (1966), ponders the vague relationships between science, arts, conceptualization, teaching methods, and organizations. Dr. Knowles reconsiders the history of the present dilemma, discusses why intellectual excitement has not been part of
Patient care is at risk as NHS faces substantial deficit, says think tank
Authors: G. Iacobucci
Journal: BMJ (2015)

The performance of the NHS in England has rapidly deteriorated under the coalition government in the past two years, a major report from a leading healthcare think tank has said.1

In its assessment of the NHS’s performance since the coalition was formed in 2010, the King’s Fund said that although performance held up well for the first three years of the parliament, the service was now under huge strain, with a real risk that care of patients will suffer as the NHS heads towards a substantial deficit. It said that waiting times were at their highest levels for several years and warned that the current funding gap could lead to “an accelerating decline in NHS performance” if it is not tackled in the next parliament.

The report is the second in a two part assessment of the coalition’s record on the NHS in the run up to May’s general election, the first …
Cost effectiveness of lowering cholesterol concentration with statins in patients with and without pre-existing coronary heart disease: life table method applied to health authority population
Authors: P D P Pharoah, W Hollingworth
Journal: BMJ (1996)

To estimate the cost effectiveness of statins in lowering serum cholesterol concentration in people at varying risk of fatal cardiovascular disease and to explore the implications of changing the criteria for intervention on cost and cost effectiveness for a purchasing authority.A life table method was used to model the effect of treatment with a statin on survival over 10 years in men and women aged 45-64. The costs of intervention were estimated from the direct costs of treatment, offset by savings associated with a reduction in coronary angiographies, non-fatal myocardial infarctions, and revascularisation procedures. The robustness of the model to various assumptions was tested in a sensitivity analysis.Population of a typical district health authority.Cost per life year saved.The average cost effectiveness of treating men aged 45-64 with no history of coronary heart disease and a cholesterol concentration > 6.5 mmol/l for 10 years with a statin was 136,000 pounds per life year saved. The average cost effectiveness for patients with pre-existing coronary heart disease and a cholesterol concentration > 5.4 mmol/l was 32,000 pounds. These averages hide enormous differences in cost effectiveness between groups at different risk, ranging from 6000 pounds per life year in men aged 55-64 who have had a myocardial infarction and whose cholesterol concentration is above 7.2 mmol/l to 361,000 pounds per life year saved in women aged 45-54 with angina and a cholesterol concentration of 5.5-6.0 mmol/l.Lowering serum cholesterol concentration in patients with and without preexisting coronary heart disease is effective and safe, but treatment for all those in whom treatment is likely to be effective is not sustainable within current NHS resources. Data on cost effectiveness data should be taken into account when assessing who should be eligible for treatment.
Inhibition of In Vivo Insulin Secretion by Prostaglandin E1
Authors: R. Paul Robertson, David J. Gavareski, Daniel Porte, Edwin L. Bierman
Journal: Journal of Clinical Investigation (1974)

To determine the effect of prostaglandin E(1) (PGE(1)) infusion upon in vivo insulin secretion, serum insulin responses after an intravenous glucose pulse (2 g) were measured before and during an intravenous infusion of PGE(1) (10 mug/min) in 11 anesthetized dogs. Circulating insulin decreased significantly during PGE(1) infusion were significantly less than control responses. Three dogs received PGE(1) infusions into the thoracic aorta to preclude pulmonic and hepatic degradation of PGE(1) before its arrival at the pancreatic artery; inhibition of insulin secretion was again seen. Inhibition of insulin secretion could not be related to the degree of arterial hypotension induced by intravenous PGE(1), and despite alpha adrenergic blockade with intravenous phentolamine, PGE(1)-induced inhibition of glucose-stimulated insulin responses persisted. Significant increments in systemically circulating PGE levels during intravenous PGE(1) infusions were documented by radioimmunoassay. These studies demonstrate that systemic PGE(1) infusion inhibits insulin secretion and that this effect could not be shown to be dependent upon alpha adrenergic activity.
Maternal Famine, De Novo Mutations, and Schizophrenia
Authors: Jack M. McClellan, Ezra Susser, Mary-Claire King
Journal: JAMA (2006)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
DEAR1, a Novel Tumor Suppressor That Regulates Cell Polarity and Epithelial Plasticity
Authors: Nanyue Chen, Seetharaman Balasenthil, Jacquelyn Reuther, Ann McNeill Killary
Journal: Cancer Research (2014)

Abstract Elucidation of the regulatory controls on epithelial plasticity is pivotal not only to better understand the nature of metastasis but also for the design of targeted therapies to prevent the earliest steps in migration and invasion from the primary tumor. This review will highlight the role of the novel TRIM protein DEAR1 (annotated as TRIM62) in the regulation of apical–basal polarity and acinar morphogenesis as well as its function as a chromosome 1p35 tumor suppressor and negative regulator of TGFβ-driven epithelial–mesenchymal transition (EMT). DEAR1 binds to and promotes the ubiquitination of SMAD3, the major effector of TGFβ-mediated EMT, as well as downregulates SMAD3 targets SNAIL1/2, master transcriptional regulators of EMT. Cumulative results suggest a novel paradigm for DEAR1 in the regulation of the breast tumor microenvironment, polarity, and EMT. Because DEAR1 undergoes loss-of-function mutations, homozygous deletion, as well as copy-number losses in multiple epithelial cancers, including breast cancer, DEAR1 has clinical use as a predictive and prognostic biomarker as well as for stratifying breast cancers and potentially other epithelial tumor types for targeted therapies aimed at the pathways regulated by DEAR1. Cancer Res; 74(20); 5683–9. ©2014 AACR.
Molecular Mechanisms of Endothelin-1–Induced Cell-Cycle Progression
Authors: Etsu Suzuki, Daisuke Nagata, Masao Kakoki, Hiroshi Hayakawa, Atsuro Goto, Masao Omata, Yasunobu Hirata
Journal: Circulation Research (1999)

Abstract —Although it is well established that endothelin-1 (ET-1) has not only vasoconstrictive effects but also mitogenic effects, which seem to be implicated in vascular remodeling, little is known about the molecular mechanisms by which ET-1 induces cell-cycle progression. In this study, we examined the effects of ET-1 on the cell-cycle regulatory machinery, including cyclins, cyclin-dependent kinase (cdk), and cdk inhibitors in NIH3T3 cells. ET-1 increased cyclin D1 protein (5.1±1.9-fold increase, 8 hours after stimulation, P &lt;0.05), cdk4 kinase activity (2.8±0. 5-fold increase, 12 hours after stimulation, P &lt;0.01), and cdk2 kinase activity (2.1±0.4-fold increase, 16 hours after stimulation, P &lt;0.05) in a time- and dose-dependent manner. ET-1–induced increase in cyclin D1 protein, and cdk4 kinase activity was not significantly inhibited by an inhibitor of the mitogen-activated protein kinase kinase 1/2, PD98059, nor by the protein kinase C inhibitor calphostin C, whereas ET-1–induced upregulation of cyclin D1 protein and cdk4 kinase activity was significantly inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. In contrast, ET-1–induced activation of cdk2 kinase was significantly inhibited by PD98059, calphostin C, and LY294002. ET-1 increased 3 H-thymidine uptake in a time-dependent fashion (0 hours, 4216±264 cpm per well; 8 hours, 5025±197 cpm per well; 16 hours, 9239±79 cpm per well, P &lt;0.001 versus 0 hours). ET-1–induced increase in 3 H-thymidine uptake was significantly inhibited by PD98059, calphostin C, and LY294002. These results suggest that ET-1–induced cell-cycle progression is, at least in part, mediated by the extracellular signal-regulated kinase, protein kinase C, and phosphatidylinositol 3-kinase and that those pathways may be involved in the progression of the cell cycle at distinct points.
Asthma unresponsive to simple treatment in a child
Authors: Niamh O’Carroll, John Fitzsimons, Siobhán Carr
Journal: BMJ (2008)

A 7 year old boy with recurrent wheeze was diagnosed with asthma six months ago. He was started on two metered dose inhalers: a short acting β2 agonist, as required, and an inhaled corticosteroid 100 μg (beclometasone diproprionate equivalent) twice daily. When his symptoms continued his steroid inhaler was increased to 200 μg twice daily, but he presents to the surgery with regular wheeze.

Assess control of wheeze, cough, nights disturbed, absence from school, and interference with play or exercise. Assess frequency of use of short acting β2 agonists and courses of oral steroids. Ask about emergency consultations or hospital attendances and possible triggers, especially smoking and common allergens such as dust mite, pet dander, and pollens, as well as viral infections, exercise, cold air, emotional upset, and non-steroidal anti-inflammatory drugs. Ask about school: can he use the inhalers with …
Relationship between Concentrations of Maternal Plasma Oestrogens and Progesterone and Response to Artificial Rupture of Membranes
Authors: M. M. Shaaban, V. Jandial, A. Klopper
Journal: BMJ (1974)

The concentrations of oestradiol-17β, oestriol, and progesterone were measured in the plasma of 100 patients at the time of induction of labour by artificial rupture of membranes. There was no statistically significant difference in the hormone concentration or in the ratio of oestrogens to progesterone between patients who went into labour after rupture of the membranes and those who did not. Nor was there any significant difference in the hormone values between oxytocin-sensitive and oxytocin-insensitive patients.
Possible role of the adrenergic mechanism in gastric inhibitory polypeptide-and glucagon-like peptide-1 (7–36) amide-induced insulin release in the rat
Authors: Tadasu Ikeda, Hiroshi Ochi, Izumi Ohtani, Katsumi Fujiyama, Tazue Hoshino, Yasushi Tanaka, Tatsuo Takeuchi, Hiroto Mashiba
Journal: Metabolism (1993)
Legal aid withdrawn from negligence cases
Authors: C. Dyer
Journal: BMJ (1997)

The Lord Chancellor, Lord Irvine, has announced a wide ranging shake up of legal aid and civil justice, which will have far reaching repercussions for medical negligence litigation in England and Wales.

Legal aid is to be withdrawn from all money and damages claims, including medical negligence. The government expects lawyers to fill the gap by a big expansion of “no win, no fee” deals (in which the loser pays the winner's costs). But the Bar and the Law Society warn that the high costs that …
The Medial Wall of the Right Atrium
Authors: ROBERT WALMSLEY, HAMISH WATSON
Journal: Circulation (1966)

The correct orientation of the heart in situ has been stressed and the anatomic relationships of the medial wall of the right atrium have been described and illustrated. Each atrium lies behind and to the right of its corresponding ventricle and, as the plane of the septa is angled at approximately 45° to the median plane, the right atrium lies as much in front of the left atrium as alongside it. The area of overlap between the atria is small in both the anteroposterior and lateral views and the interatrial septum, which constitutes only the posterior half of the medial wall of the right atrium, is most accessible in the right anterior oblique projection. The anterior half of the medial wall of the right atrium is closely related from above downward to the first part of the aorta including the aortic valve, and to the left ventricular outflow tract through the membranous part of the interventricular septum. The right coronary artery and the right ventricular outflow tract are also important anterior relations. Transverse sections of the thorax in all age groups have shown that only one aortic valve cusp is truly anterior and it is suggested that the terms anterior, and right and left posterior should be used to designate the cusps and sinuses of the aortic valve.
Treatment of Benign Prostatic Hyperplasia and Occurrence of Prostatic Surgery and Acute Urinary Retention: A Population-Based Cohort Study in The Netherlands
Authors: P.C. Souverein, M.M. van Riemsdijk, J.J.M.C.H. de la Rosette, P.C.E. Opdam, H.G.M. Leufkens
Journal: European Urology (2004)
Management of hypertension. Effect of improving patient compliance for follow-up care
Authors: S. W. Fletcher
Journal: JAMA (1975)

A radomized controlled trial was conducted in a metropolitan teaching hospital to determine whether improving follow-up of emergency room patients who had hypertension led to improvements in their medical care and blood pressure control. One hundred fourty four patients were randomly assigned into an intervention group and a control group. In the former, a follow-up clerk assigned patients in returning for follow-up care. Eighty-four percent of patients in this group and 63% of control patients returned to the clinic (P less than 0.1). However, five months after the patients' emergency room visits, 51% of patients in the intervention group and 53% of control patients were normotensive. There were more diagnostic and therapeutic measures in the intervention group, but long-term management was similar in both groups. Improvement in follow-up may not be by itself lead to blood pressure control among hypertensive patients.