tbuckley/cabot-search huggingface dataset:
Abstract 3823: 2-Methyl-6-substituted pyrrolo[2,3-d]pyrimidine classical antifolates as selective folate receptor substrates, glycinamide ribonucleotide formyltransferase inhibitors and antitumor agents
Authors: Aleem Gangjee, Sai Zhao, Lei Wang, Steven Orr, Erika Etnyre, Sudhir Raghavan, Larry H. Matherly, Roy L. Kisliuk
Journal: Cancer Research (2012)

Abstract The important role of reduced folates in one-carbon transfer reactions has rendered folate metabolism an attractive target in cancer chemotherapy for decades. Clinically used antifolates enter cells via folate uptake systems, such as the reduced folate carrier (RFC), folate receptors (FRs), and the proton-coupled folate transporter (PCFT). Toxicity of clinically used antifolates is due to their lack of selectivity for tumor cells, since these antifolates are transported by RFC which occurs in normal as well as tumor cells. FRs are not usually expressed in normal cells. However, the ≤ isoform of FR is abundantly expressed in certain tumor cells, such as ovarian, endometrial, etc. Thus, selective FR-targeted antifolates that also possess cytotoxic activity without transport by RFC would likely circumvent the major toxicities of currently used antifolates. 2-Methyl-6-substituted pyrrolo[2,3-d]pyrimidine antifolates were designed to evaluate the importance of the 2-amino group for transport by RFC, FR, and /or PCFT, as well as for inhibition of α-glycinamide ribonucleotide formyltransferase (GARFTase) in de novo purine biosynthesis, compared with the 2-amino analogs. The most active compound in our series, AG179, showed an IC50 of 1.6 nM in inhibiting proliferation of KB human tumor cells, and was ∼3-fold less potent than the corresponding 2-amino compound AG71 (0.55 nM). In Chinese hamster ovary (CHO) cells engineered to individually express the major folate transporters, AG179 also inhibited growth of FRα-expressing RT16 cells but was inactive toward RFC-expressing PC43-10 and PCFT-expressing R2/PCFT4 CHO cells. The 2-amino analog, AG71, is inert toward RFC but is avidly transported by PCFT and is cytotoxic toward PCFT-expressing cells. In KB cells, growth inhibition by AG179 like AG71 is protected by excess adenosine and 5-amino-4-imidazole carboxamide, establishing GARFTase and de novo purine biosynthesis as the likely intracellular targets. These results establish that replacement of the 2-amino group of AG71 with a methyl group has a limited impact on FRα uptake and anti-proliferative activity, however, this replacement has a profound impact on cellular uptake by PCFT. This report will present the details of the design, synthesis, biological evaluation and molecular modeling of the title compounds. 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 3823. doi:1538-7445.AM2012-3823
MICRORNAS CONTROL ENDOTHELIAL PROGENITOR SENESCENCE VIA REGULATING HMGA2 EXPRESSION
Authors: Shoukang Zhu, Shanming Deng, Qi Ma, Taifang Zhang, Degen Zhuo, Liyong Wang, Pascal J. Goldschmidt, Chunming Dong
Journal: Journal of the American College of Cardiology (2011)
Unilateral pulmonary artery thrombotic occlusion: is distal arteriopathy a consequence?
Authors: A M Hirsch, K M Moser, W R Auger, R N Channick, P F Fedullo
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The characteristics and postoperative outcomes of a unique group of eleven patients with total unilateral pulmonary artery (PA) thromboembolic occlusion were compared with those of some 400 patients who underwent bilateral thromboendarterectomies during the same time period. Preoperative historical, physical, and laboratory features and postoperative outcomes of these two groups were analyzed. The unilateral group had no distinct historical features. However, they were younger (32 +/- 10 yr) than the bilateral group (51 +/- 15 yr), dominantly female (10 of 11) versus a male predominance (62%) in the bilateral group; had significantly lower preoperative PA mean pressures (30 +/- 12 versus 46 +/- 12 mm Hg) and calculated pulmonary vascular resistance (360 +/- 293 versus 901 +/- 467 dynes/s/cm-5); and small lung by chest radiograph was common (8 of 11). Postoperatively, four unilateral patients developed unilateral rethrombosis (two immediate; two late, at several years postsurgery); this occurred in only one bilateral patient. Furthermore, of six patients with unilateral occlusion present more than 1 yr, reperfusion was poor in four despite an adequate thromboendarterectomy in all. Postoperative pulmonary angiograms in two of these disclosed apparent atrophy of central and distal pulmonary arteries. Prior animal investigation models indicate that unilateral PA occlusion is followed by development of a postobstructive arteriopathy in the resistance arteries of the occluded lung. The unusual outcomes in these 11 patients suggest that they may develop a similar arteriopathy which requires special management considerations at surgery and postoperatively.
Comprehensive analysis of homeobox genes in Hodgkin lymphoma cell lines identifies dysregulated expression of HOXB9 mediated via ERK5 signaling and BMI1
Authors: Stefan Nagel, Christof Burek, Letizia Venturini, Michaela Scherr, Hilmar Quentmeier, Corinna Meyer, Andreas Rosenwald, Hans G. Drexler, Roderick A. F. MacLeod
Journal: Blood (2006)
Prostate Cancer Screening
Authors: Roger Luckmann
Journal: Annals of Internal Medicine (2001)

Medical Writings: Book Notes4 December 2001Prostate Cancer ScreeningRoger Luckmann, MD, MPHRoger Luckmann, MD, MPHDepartment of Family Medicine and Community Health, University of Massachusetts Medical School, Worcester, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-135-11-200112040-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Thompson IM, Resnick MI, Klein EA, eds. 336 pages. Totowa, NJ: Humana Pr; 2001. $99.50. ISBN 0896039013. Order phone 973-256-1699.Field of medicine: Preventive medicine and oncology.Audience: Primary care physicians, patients, and health policymakers.Purpose: To provide a detailed, balanced discussion of key issues related to prostate cancer screening as an aid to individual and organizational screening decisions.Content: Review of screening and diagnostic methods for prostate cancer (prostate-specific antigen [PSA], transrectal ultrasound [TRUS], and others), epidemiology of prostate cancer, summary of selected studies on screening effectiveness, commentaries for and against screening, presentation of prostate cancer risk index, and ... Author, Article, and Disclosure InformationAffiliations: Department of Family Medicine and Community Health, University of Massachusetts Medical School, Worcester, Massachusetts. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 December 2001Volume 135, Issue 11Page: 1018KeywordsCancer screeningMedical risk factorsPatientsPrevention, policy, and public healthPreventive medicinePrimary care physiciansProstate cancerRisk assessmentsSoftware toolsTransrectal ultrasound ePublished: 4 December 2001 Issue Published: 4 December 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
New patients’ forums will lack any real clout, says BMA
Authors: Caroline White
Journal: BMJ (2008)

The new system in England to represent patients’ and public opinion on health and social care is poorly resourced, insufficiently independent, and unlikely to be able to exercise any real clout, claims the BMA.

In the second of its reports on the future of the NHS in England the BMA raises several concerns about local involvement networks (LINKs), which will replace patient and public involvement forums next month.

The new networks will enable commissioners, regulators, and local authorities’ overview and scrutiny committees to gauge public opinion on health and …
Cancer Information Service Renewed
Authors: J. A. Steele
Journal: JNCI Journal of the National Cancer Institute (1990)

Cancer Information Service Renewed Get access Julie A. Steele Julie A. Steele Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 5, 7 March 1990, Page 353, https://doi.org/10.1093/jnci/82.5.353 Published: 07 March 1990
Medical and Surgical History of the War.
Authors: H. G. Graham
Journal: JAMA (1896)

<h3>To the Editor:</h3> —Has there been a law passed for printing a new revision on the Medical and Surgical History of the War of the Rebellion which are to be distributed among the profession through the Congressmen in their districts? The Indiana State Board of Health moved for this bill for a new edition at their last meeting. <h3>Answer:</h3> The work has not been republished.
Allocating census data to general practice populations
Authors: G. Scrivener, D. C Lloyd
Journal: BMJ (1996)

cycles of either mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin.Nine thousand patients will be required for the trial to give a reliable and clinically relevant result.Potentially all patients with non-small cell lung cancer will be eligible.Similar large trials have been conducted in breast and ovarian cancer, with considerable success.The "big lung trial" will be the first large scale randomised trial to ask this basic but important question about the treatment of this major disease.
TPMT in the treatment of inflammatory bowel disease with azathioprine
Authors: A Qasim
Journal: Gut (2003)

We read with interest the recent article by Lennard on the role of thiopurine methyltransferase (TPMT) enzyme in predicting azathioprine related toxicity in patients with inflammatory bowel disease (IBD) ( Gut 2002; 51 :143–6). He concludes that measurement of TPMT activity has no specific role in identifying the risk of significant bone marrow toxicity in long term users of azathioprine. This conclusion is in agreement with other published work and emphasises the importance of ongoing haematological monitoring in IBD patients receiving this drug.1 The importance of haematological monitoring in the early detection and prevention of azathioprine related toxicity is well recognised.2 However, the duration of early monitoring is a matter of controversy. The current British National Formulary guidelines recommend that patients undergo blood tests on at least a weekly basis for the initial four weeks of therapy. The drug’s manufacturers recommend a more stringent monitoring policy and in their view, initial monitoring should continue for the first eight weeks of treatment. The American College of Gastroenterology guidelines recommend a slightly different approach, with fortnightly blood counts for the initial three months of therapy.3 The key issue in determining the value of these different approaches to monitoring is the time of onset of potentially life threatening bone marrow suppression following initiation of azathioprine treatment. These data are not available for patients with IBD.

In a retrospective study, we analysed the time of onset of all drug related toxicity …
Treatment of Difficult Bile Duct Stones Using Mechanical, Electrohydraulic and Extracorporeal Shock Wave Lithotripsy
Authors: K. F. Binmoeller, M. Brückner, F. Thonke, N. Soehendra
Journal: Endoscopy (1993)

Over a 34-month period (1989-1991), 791 patients were diagnosed at endoscopic retrograde cholangiography to have bile duct stones. All patients underwent sphincterotomy and attempted extraction by Dormia basket. This was successful in 683 patients (86%). The remaining 108 patients with "difficult stones" (mean age 72 years) underwent mechanical, electrohydraulic or extracorporeal shock wave lithotripsy according to the following algorithm: (1) Mechanical lithotripsy for stones which could not be extracted after entrapment in the Dormia basket (n = 33); (2) peroral cholangioscopic electrohydraulic lithotripsy for stones which could not be engaged in the Dormia basket (n = 65); or (3) extracorporeal shock wave lithotripsy for intrahepatic stones (n = 10). Stone fragmentation and clearance was successful in all patients treated by mechanical lithotripsy, was unsuccessful in one patient submitted to electrohydraulic lithotripsy due to inability to insert the cholangioscope into the bile duct and failed in 3 patients treated by extracorporeal shock wave lithotripsy. Overall, 95% of difficult bile duct stones refractory to conventional endoscopic basket extraction were removed using the above lithotripsy techniques. There were no serious procedure-related complications.
FUTURE OF COUNTY HEALTH WORK IN THE UNITED STATES
Authors: W. G. SMILLIE
Journal: JAMA (1927)

Prophecy is hazardous. It is so much simpler to assemble our information, state what has occurred in the past, and allow each one to draw his own conclusions as to what will probably occur in the future. At times, however, certain facts stand out so vividly that we are forced to draw at least a tentative conclusion from our past experience and project the results of this conclusion into our future programs. In considering the growth and development of county health work in the United States, certain facts stand out which are acceptable to all—a common ground on which our thesis may be built. Every one is agreed that local full-time health service in the United States with the county as the administrative unit has passed the experimental stage and is now established on a firm basis. Dec. 31, 1926, there were 341 county health units in the United States,
The emerging role of T cell immunoglobulin mucin-1 in the mechanism of liver ischemia and reperfusion injury in the mouse
Authors: Yoichiro Uchida, Bibo Ke, Maria Cecilia S. Freitas, Haofeng Ji, Danyun Zhao, Elizabeth R. Benjamin, Nader Najafian, Hideo Yagita, Hisaya Akiba, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski
Journal: Hepatology (2009)

The T cell immunoglobulin and mucin domain-containing molecules (TIM) protein family, which is expressed by T cells, plays a crucial role in regulating host adaptive immunity and tolerance. However, its role in local inflammation, such as innate immunity-dominated organ ischemia–reperfusion injury (IRI), remains unknown. Liver IRI occurs frequently after major hepatic resection or liver transplantation. Using an antagonistic anti–TIM-1 antibody (Ab), we studied the role of TIM-1 signaling in the model of partial warm liver ischemia followed by reperfusion. Anti–TIM-1 Ab monotherapy ameliorated the hepatocellular damage and improved liver function due to IR, as compared with controls. Histological examination has revealed that anti–TIM-1 Ab treatment decreased local neutrophil infiltration, inhibited sequestration of T lymphocytes, macrophages, TIM-1 ligand–expressing TIM-4+ cells, and reduced liver cell apoptosis. Intrahepatic neutrophil activity and induction of proinflammatory cytokines/chemokines were also reduced in the treatment group. In parallel in vitro studies, anti–TIM-1 Ab suppressed interferon-γ (IFN-γ) production in concanavalin A (conA)–stimulated spleen T cells, and diminished tumor necrosis factor α (TNF-α)/interleukin (IL)-6 expression in a macrophage/spleen T cell coculture system. This is the first study to provide evidence for the novel role of TIM-1 signaling in the mechanism of liver IRI. TIM-1 regulates not only T for the role of cell activation but may also affect macrophage function in the local inflammation response. These results provide compelling data for further investigation of TIM-1 pathway in the mechanism of IRI, to improve liver function, expand the organ donor pool, and improve the overall success of liver transplantation. (HEPATOLOGY 2010.)
P76 The effect of outside temperature on daily physical activity in COPD patients
Authors: AD Alahmari, GC Donaldson, ARC Patel, BS Kowlessar, AJ Mackay, R Singh, JA Wedzicha
Journal: Thorax (2012)

<h3>Introduction</h3> COPD is characterised by breathlessness, leading to reduced physical activity. Breathlessness varies dependent upon the degree and intensity of physical activity (1). Common logic dictates that weather variation such as temperature and sunshine could influence physical activity in the general population, especially walking. The aims of this study were to evaluate the effect of weather variation on daily activity and the variation in activity during the days of the week in COPD patients. <h3>Methods</h3> Fifty-five stable COPD outpatients from the London COPD cohort wore a pedometer (Yamax Digi-Walker SW-200) daily for 30 days during waking hours. We excluded exacerbating patients and those using walking sticks or oxygen. All patients were asked to record their step count on daily diary cards. Weather data for London Heathrow were obtained with permission from the British Atmospheric Data Centre. Stable COPD was defined as having no symptom-defined exacerbations in the preceding six weeks and subsequent two weeks, according to prospectively-collected diary cards, with no change in long-term inhaled and oral medications in the preceding two weeks. <h3>Results</h3> The clinical characteristics of the 55 patients were mean (±SD) age 70.3 (8.7) years; FEV1% predicted 51.0% (±14.1); male gender 67%; current smoker 25%, BMI 27.2 kg/m2. The mean (±SD) daily step count was 4327 (±2944). COPD patients were more active as temperatures increased (Figure 1A) and on sunny as opposed to no sunshine days (Figure 1B, p&lt;0.001). Figure 1C shows that mean weekday activity is significantly higher than mean weekend activity (p&lt;0.001), mainly due to less activity on Sunday. <h3>Conclusion</h3> Daily activity in stable COPD markedly affected by outdoor temperature and sunshine and patients had highest activity during weekdays. Further work is required to ascertain whether some patients are more active than others. <h3>Reference</h3> Pitta F <i>et al</i>., Quantifying Physical Activity in Daily Life with Questionnaires and Motion Sensors in COPD, ERJ 27, no. 5 (April 2006): 1040–1055.
Enzyme activity may hold key to cataract prevention
Authors: Helene Cole
Journal: JAMA (1985)

"The principal and perhaps only disease of the human lens is the opacification of the lens—a cataract. However, approximately 60% of persons between the ages of 65 and 74 [years] in the United States show some signs of cataract development, and cataracts are the leading cause of blindness in Africa," reported William Rathbun, PhD, associate professor, Department of Ophthalmology, University of Minnesota Medical School, Minneapolis, in discussing "The Achilles Heel of the Human Lens" at the Research to Prevent Blindness seminar in Washington, DC. Cataracts may be unavoidable. Ultraviolet light, present in sunlight and many forms of artificial light—when incident on the lens—produces free radicals and oxidation products such as hydrogen peroxide, that lead to the development of cataracts. An apparent defense mechanism in the young, healthy lens is a tripeptide—glutathione. Work in Rathbun's laboratory has demonstrated that the glutathione content of the lens decreases with age. That "concentration has
HCV deffection in “autonimine” chronic active hepatitis
Authors: S. Magrin, A. Craxi, P. Almasio, C. Fabiano, G. Fiorentino, U. Palazzo, G.B. Pinzello, G. Provenzeno, L. Pagliaro, M. Houghton, J.H. Han
Journal: Journal of Hepatology (1990)
Delayed Idiosyncratic Psychosis With Phenytoin
Authors: Vernon H. Mark
Journal: JAMA (1975)

<h3>To the Editor.—</h3> The clinical note by McDanal and Bolman (231:1063, 1975) raises some interesting points. It is always tempting to postulate a cause and effect relationship between medication and symptom if the symptom disappears when the medication is withdrawn. However, this explanation, ie, that a paranoid psychosis was produced by an idiosyncratic reaction to phenytoin, must be evaluated in the context of the patient's disease state. The authors reported their patient to have had long-standing epileptic seizures, and the patient's husband is quoted as reporting the patient to have had symptoms of violent behavior even when the florid psychosis had disappeared. This makes one suspect that the patient's epileptic process involves her limbic system. The literature is replete with references to various forms of epileptic disease associated with abnormal behavior. The classic monograph of Slater et al<sup>1</sup>in 1963 described certain forms of epilepsy that seemed to predispose
Systemic Lupus Erythematosus
Authors: Sarah Ringold, Cassio Lynm, Richard M. Glass
Journal: JAMA (2011)

Systemic Lupus Erythematosus"Butterfly" rash S ystemic lupus erythematosus (SLE), also called lupus, is an autoimmune disorder in which the body's immune system (the cells in the body that fight infection) incorrectly attack the body's own tissues and organs, leading to inflammation and damage.Lupus most commonly affects women of childbearing age but also occurs in children, adolescents, and men.The cause of lupus is unknown, but it has been associated with genetic, environmental, and infectious causes.The disorder may affect almost all organs in the body.It may be mild in some cases (for example, involving only the skin) and very severe in other cases (affecting multiple organs, including the brain).The disease course is characterized by flares (intervals of active disease) and remissions (intervals of inactive disease).This Patient Page is based on one published in the June 22/29, 2005, issue of JAMA.
HEMORRHAGE FROM THE STUMP FOLLOWING APPENDECTOMY.WITH A REPORT OF THREE CASES.
Authors: WILLIAM HESSERT
Journal: JAMA (1906)

It has been my misfortune, during the year past, to have had three cases of postoperative bleeding from the stump following appendectomy, with a fatal issue in one instance. An experience of this kind would naturally lead one to ponder over the cause of the accident and to change the technic if found to be at fault. My method in the past had been the widely practiced one of clamping the appendix at its base, cutting off the distal portion flush with the forceps, inserting a purse-string suture around the base, releasing the forceps and inverting the stump while the suture is tied. The case histories are as follows:  Case 1.  —Female, aged 13.  History.  —The patient has had four attacks of appendicitis during the past two years, all mild in character. The present attack began with severe pain in the right iliac fossa, vomiting and constipation.  Examination.  —I saw
Eosinophilic gastrointestinal disease suggestive of pathogenesis-related class 10 (PR-10) protein allergy resolved after immunotherapy
Authors: Liliane De Swert, Geneviève Veereman, Merima Bublin, Heimo Breiteneder, Ellen Dilissen, Eugene Bosmans, Caroline Mattelaer, Dominique Bullens
Journal: Journal of Allergy and Clinical Immunology (2013)