tbuckley/cabot-search huggingface dataset:
Abstract LB-491: PD-1 expression level on T cell subsets is a crucial factor forming a novel mechanism for designing immune therapeutic approaches using PD-1 binding ligand
Authors: Mikayel Mkrtichyan, Yana G. Najjar, Estella C. Raulfs, Linda Liu, Solomon Langerman, Samir N. Khleif
Journal: Cancer Research (2012)

Abstract A significant barrier to tumor regression in the setting of a successful immune response is tumor-mediated immunosuppression. Programmed death receptor-1 (PD-1) is an important signaling molecule and in the context of the tumor microenvironment may inhibit T cell immunity when bound to its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), by inducing T cell apoptosis and anergy. Recently we demonstrated that combination of anti-PD-1 antibody with vaccine and low-dose of cyclophosphamide (CPM), that reduces the number and function of Treg cells, significantly enhances antigen-specific immune responses, decreases tumor burden and increases survival of treated mice, suggesting that targeting multiple immune checkpoint inhibitors is a promising strategy for tumor immunotherapy. Here we tested the anti-tumor immune effect of B7-DC-Ig, a recombinant protein that binds and target PD-1. It is composed of the extracellular domain of B7-DC, fused to the Fc portion of murine IgG2a. We demonstrated that B7-DC-Ig can enhance the therapeutic efficacy of a peptide based cancer vaccine when combined with CPM. We showed that this combination significantly enhances antigen-specific immune responses and leads to complete eradication of established tumors in 60% of mice and that this effect is CD8 dependent. Importantly, we found that unlike anti-PD-1 antibody, B7-DC-Ig does not block the suppressive PD-1/PD-L1 interaction as its primary mechanism, and identified a novel mechanism by which B7-DC-Ig exerts its therapeutic effect. We demonstrate, for the first time, that there are significant differences between levels and timing of surface PD-1 expression on different T cell subsets. We found that these differences play a critical role in the anti-tumor effects exhibited by B7-DC-Ig through inhibiting proliferation of dysfunctional PD-1high CD4 T cells, for both Treg and FoxP3−T cells, leading to a significant decrease in levels of tumor infiltration by dysfunctional T cells. In addition, we showed that treatment with B7-DC-Ig also leads to a decrease in PD-1highCD8 T cells, tipping the balance towards non-exhausted, functional PD-1lowCD8 T cells. Aside from presenting a promising anti-tumor immunotherapeutic approach, we demonstrated that the level of PD-1 expression on different T cells subsets determines the “effective target zone” of B7-DC-Ig. We believe that this represents an important parameter that needs to be considered to favorably alter the tumor microenvironment when designing PD-1 targeting immune therapies. 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 LB-491. doi:1538-7445.AM2012-LB-491
Induction of resistance to Schistosoma mansoni infection in mice by purified parasite paramyosin.
Authors: T P Flanigan, C H King, R R Lett, J Nanduri, A A Mahmoud
Journal: Journal of Clinical Investigation (1989)

Freeze-thaw (FT)-disrupted schistosomula or their membrane extract induced significant resistance in mice to Schistosoma mansoni infection (34 and 25%, respectively) without the use of adjuvant. Antigens identified in schistosome extracts by sera from immunized animals were then evaluated for protective potential. Immunization with schistosomal antigens of 97 and 68-70 kD resulted in significant protection that was equivalent to that obtained by FT schistosomula. Since the 97-kD antigen was suggested to be parasite paramyosin, we used a biochemical technique to purify this muscle protein. Purified schistosome paramyosin ran as a single band on 10% SDS-PAGE and was recognized both by sera from mice immunized with FT schistosomula and a polyclonal antiserum raised against the 97-kD parasite protein. Preincubation of schistosome paramyosin with sera from mice immunized with FT schistosomula resulted in the removal of reactivity with the 97-kD protein in crude worm extracts. Paramyosin was identified by Western blotting to be in the tegument of schistosomula. The purified schistosome paramyosin resulted in significant protection in three separate experiments (24, 46, and 53%) without the use of adjuvant. Addition of BCG to paramyosin resulted in enhanced protection.
Drug eluting coronary stents
Authors: N P Jenkins
Journal: BMJ (2002)

Percutaneous coronary revascularisation has revolutionised the treatment of ischaemic heart disease during the past two decades. Despite technical refinements, however, long term results after using standard techniques remain limited by the phenomenon of restenosis—a process whereby elastic recoil and neointimal hyperplasia occur at the site of endothelial injury, often resulting in recurrent symptoms within six months of the procedure. Although the use of coronary stents is associated with lower rates of restenosis than balloon angioplasty alone,1 rates of up to 40% have been reported in some series, and treatment options are often unsatisfactory, with high recurrence rates after further intervention.2

Neointimal hyperplasia begins soon after coronary intervention as a result of platelet activation, inflammation, and proliferation of smooth muscle cells. Pharmacological inhibition of these processes by using drugs administered systemically has had little success in preventing restenosis. A platelet IIb/IIIa receptor antagonist, abciximab, has shown a modest benefit for patients with diabetes mellitus undergoing stent implantation,3 but trials of other drugs have often failed spectacularly despite promising preliminary work in animal models. Intravascular radiation (brachytherapy) using sources emitting γ rays or β rays is an effective way of treating established restenosis, 4 5 although its use for the prevention …
Sexual dimorphism in vasopressin and cardiovascular response to hemorrhage in the rat.
Authors: J T Crofton, L Share
Journal: Circulation Research (1990)

There is evidence for sex-related differences in the cardiovascular actions of vasopressin. Furthermore, receptors for the gonadal steroid hormones are located in centers in the brain involved in the control of vasopressin release and in cardiovascular regulation. We have, therefore, examined the effects of hemorrhage on mean arterial blood pressure, the plasma vasopressin concentration, and plasma renin concentration in conscious male and female rats. In preliminary experiments, no differences were found in blood and plasma volumes with respect to either sex or phase of the estrous cycle. In separate experiments, rats were subjected to two hemorrhages of 10% of blood volume, separated by an interval of 15 minutes. There were no substantial gender- or cycle-related differences in the ability of hemorrhaged rats to maintain mean arterial blood pressure or increase plasma renin concentration. The increase in plasma vasopressin concentration was greater in proestrous females than in males after the first hemorrhage and in diestrous, proestrous, and metestrous females than in males after the second hemorrhage. Pretreatment with a V1-receptor antagonist was without statistically significant effect on the mean arterial blood pressure responses in males, but it impaired blood pressure compensation in females. There are, then, gender- and cycle-related differences in vasopressin responses to hemorrhage, and vasopressin appears particularly important for blood pressure compensation to hemorrhage in female rats.
New criteria for female athlete triad syndrome?
Authors: K M Khan, T Liu-Ambrose, M M Sran, M C Ashe, M G Donaldson, J D Wark
Journal: British Journal of Sports Medicine (2002)

Assessment and Research Centre (FIFA, F-MARC), and the International Olympic Committee Medical Commission (IOC).The aim of the symposium was to provide recommendations for the improvement of safety and health of athletes who suffer concussive injuries in ice hockey, football (soccer), and other sports.To this end a range of experts were invited to address specific issues of epidemiology, basic and clinical science, grading systems, cognitive assessment, new research methods, protective equipment, management, prevention, and long term outcome, and to discuss a unitary model for understanding concussive injury.At the conclusion of the conference, a small group of experts were given a mandate by the conference delegates and organising bodies to draft a document describing the agreement position reached by those in attendance at that meeting.For the purpose of this paper, this group will be called the Concussion in Sport Group (CISG).
Reaching the Readers: Experience With the AMA Specialty Journals
Authors: Michael D. Springer
Journal: JAMA (1990)

The average physician in the United States receives a large number of medical publications each month. Some appear because the physician deliberately bought a subscription. Some are received as a benefit of membership in one or more professional organizations. And some simply arrive in the mail as a result of "controlled circulation," because his or her name is on some list of physicians who share certain practice characteristics deemed desirable by the publisher. Conventional wisdom has held that physicians are more likely to read and value publications they have deliberately purchased. However, some time ago a substantial body of information available to the commercial world began to question that point of view. Syndicated reader research suggested high readership for some publications received on a controlled basis. Sadly, the publications with the highest scores often were not the "worthy" peer-reviewed scientific journals; instead, they were tabloids and specialty magazines that are
How Often Do <i>BRCA</i> Mutation Carriers Tell Their Young Children of the Family's Risk for Cancer? A Study of Parental Disclosure of <i>BRCA</i> Mutations to Minors and Young Adults
Authors: Angela R. Bradbury, James J. Dignam, Comfort N. Ibe, Sogyong L. Auh, Fay J. Hlubocky, Shelly A. Cummings, Melody White, Olufunmilayo I. Olopade, Christopher K. Daugherty
Journal: Journal of Clinical Oncology (2007)

Predictive genetic testing for adult-onset diseases is generally discouraged until the age at which interventions are believed to be helpful. Yet, many BRCA mutation carriers discuss their results with their children. This study describes the prevalence and experiences of parental communication of BRCA results to children under the age of 25 years old.Forty-two BRCA mutation carriers completed semistructured telephone interviews assessing self-reported disclosure to offspring and parent experiences with disclosure. Qualitative responses were coded for themes. chi(2) tests and logistic regression analyses with robust variance estimates were used to evaluate parent and child characteristics associated with disclosure.Fifty-five percent of parents reported discussing hereditary risk of cancer with at least one child. By parent report, 49% of the 86 offspring learned of their parents genetic test results or the hereditary cancer risk. Offspring age was strongly associated with disclosure (P = .001), and the majority of adolescent and adult children learned of the familial mutation or the hereditary risk of cancer. Parents reported that some offspring did not appear to understand the significance of the information shared, and that some offspring had initial negative reactions to disclosure. Physician (14%) and genetic counselor (21%) involvement in parent decisions to disclose were low.Children of BRCA mutation carriers learn of their parents genetic test results many years before preventive interventions are indicated. Further research is needed to examine how young individuals understand this information and its psychosocial impact and influence on subsequent lifestyle and health behaviors.
Reduction in distal blood pressure by sympathetic nerve block in patients with occlusive arterial disease
Authors: P. E. NIELSEN, G. BELL, G. AUGUSTENBORG, O. PAASKE-HANSEN, N. A LASSEN
Journal: Cardiovascular Research (1973)

Journal Article Reduction in distal blood pressure by sympathetic nerve block in patients with occlusive arterial disease Get access P. E. NIELSEN, P. E. NIELSEN 1 From the Departments of Clinical Physiology, Surgery (M), and Anesthesiology, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark 1Address for reprints: Dr. P. E. Nielsen, as above. Search for other works by this author on: Oxford Academic PubMed Google Scholar G. BELL, G. BELL From the Departments of Clinical Physiology, Surgery (M), and Anesthesiology, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar G. AUGUSTENBORG, G. AUGUSTENBORG From the Departments of Clinical Physiology, Surgery (M), and Anesthesiology, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar O. PAASKE-HANSEN, O. PAASKE-HANSEN From the Departments of Clinical Physiology, Surgery (M), and Anesthesiology, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar N. A LASSEN N. A LASSEN From the Departments of Clinical Physiology, Surgery (M), and Anesthesiology, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 7, Issue 5, September 1973, Pages 577–584, https://doi.org/10.1093/cvr/7.5.577 Published: 01 September 1973
Fatal Occupational Injuries-Reply
Authors: Nancy A. Stout
Journal: JAMA (1990)

In Reply.—  We agree with Dr Goldberg that fatality rates using person-years as denominators rather than workers at risk would be very useful. However, at the national level, employment data that are both based on hours worked and disaggregated by demographic and employment characteristics (eg, age, sex, race, state, occupation, industry) are not readily available on an annual basis. In fact, we had to use several different sources of denominator data to compute the various rates presented.  After we obtain complete numerator data for 1980 to 1990, we intend to calculate national traumatic occupational fatality rates based on person-time denominators from the 1980 and 1990 census. In developing the rates for this article, we felt that worker-based employment data that coincide with the time period represented by the numerator would generate more accurate rates than hourly-based denominator data that would have to be extrapolated from 1980.  The purpose of
The Financial Costs of Gun Violence
Authors: Linda Gunderson
Journal: Annals of Internal Medicine (1999)

Currents21 September 1999The Financial Costs of Gun ViolenceLinda GundersonLinda GundersonSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-6-199909210-00102 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail As is widely known, the United States leads the world in death by firearms. The Centers for Disease Control and Prevention (CDC) reported that since 1972, more than 30 000 people have died of firearm injuries each year. Injuries from firearms are the second leading cause of death for Americans 15 to 34 years of age, and the number of nonfatal firearm injuries is estimated at 84 000 annually.Less appreciated is the fact that firearms-related injury and death incur huge financial costs. These costs have been almost invisible for many reasons, but the need to define health care costs ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byChapter 1 Literature ReviewThe costs of interpersonal violence—an international review 21 September 1999Volume 131, Issue 6Page: 483-484KeywordsAlcoholsDrug abuseDrug policyDrugsFirearm injuriesHealth careHealth statisticsHomicideInfectious diseasesViolent crime Issue Published: 21 September 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.Loading ...
Biological Mechanism Associated with Asthma Exacerbation Attack as Revealed By Gene Expression Patterns of Peripheral Blood Mononuclear Cells
Authors: M.M. O'Toole, U. Bjornsdottir, S. Holgate, P.S. Reddy, A.A. Hill, C.M. McKee, C. Csimma, H.M. Legault, A. Weaver, C.G. Small
Journal: Journal of Allergy and Clinical Immunology (2009)
Prevalence of valvular-regurgitation associated with dexfenfluramine three to five months after discontinuation of treatment
Authors: Neil J Weissman, John F Tighe, John S Gottdiener, John T Gwynne
Journal: Journal of the American College of Cardiology (1999)

OBJECTIVES The goal of this study was to determine the prevalence of valvular regurgitation and abnormal valve morphology in patients three to five months after discontinuation of dexfenfluramine (Dexfen) therapy. BACKGROUND We previously reported the results of a randomized, double-blind, placebo-controlled trial of valvular structure and function in 1,073 patients treated either with Dexfen, with an investigational sustained-release dexfenfluramine (Dexfen SR), or with a placebo, with echocardiograms performed approximately one month from the last dose. Using FDA criteria (aortic regurgitation [AR] ≥mild and/or mitral regurgitation [MR] ≥moderate) we found no statistical difference among the groups, but when all degrees of valvular regurgitation were considered and when the two Dexfen groups were combined, there was a higher prevalence of any degree of AR, any degree of MR, and restricted posterior mitral leaflet mobility. However, it was unknown whether these differences in prevalence persisted. METHODS The double blind was maintained, and all patients were invited to return for a follow-up echocardiogram. Echocardiograms were acquired using a standardized protocol and assessed blindly to determine the degree of valvular regurgitation and valve leaflet thickness and mobility. We had an 80% power to detect a statistically significant change in paired proportions using the McNemar test (alpha = 0.05). RESULTS Echocardiograms were obtained on 941 patients with a median of 137 days after drug discontinuation. Aortic regurgitation (of any degree) was present in 13.8% of Dexfen (p = 0.41 compared to placebo), 10.7% of Dexfen SR (p = 0.64 compared to placebo), and 11.9% of placebo patients. The minor differences between patients treated with active drug versus placebo, which were found in the previous study, were no longer significant even when the groups were combined (p = 0.83 compared to placebo). Mitral regurgitation (of any degree) was present in 71.5% (p = 0.15 compared to placebo), 69.8% (p = 0.30 compared to placebo), and 70.5%, respectively. This was also not significantly different from placebo when both Dexfen groups were combined (p = 0.16). There was no difference in the prevalence of restricted posterior mitral leaflet mobility among the three groups (p = 0.19). CONCLUSIONS The small increase in prevalence of minor degrees of AR and MR in patients treated with two to three months of Dexfen previously reported is no longer present three to five months after discontinuation of medication. These data suggest that the degree of regurgitation observed in patients who used Dexfen for a relatively short duration does not progress over time.
Lung Uptake on Tc-99m Albumin Colloid Liver Spleen Scan and on Ga-67 Scan in Angiotropic Lymphoma
Authors: MARTA H. KACKI, JUDITH M. JOYCE, JACK J. COUPAL, U. YUN RYO
Journal: Clinical Nuclear Medicine (1990)

Lung uptake of Tc-99m sulfur colloid has been reported in various hepatic and extrahepatic diseases, and lung uptake of gallium-67 may occur in patients with various interstitial lung disease without radiographic abnormality. This may be the first case of Tc-99m albumin colloid and Ga-67 lung uptake in a patient with angiotropic lymphoma of the liver, spleen, and uterus.
George Edward Hale Enderby
Authors: David Enderby
Journal: BMJ (2004)

A pioneer of hypotensive anaesthesiaHale Enderby is best known for his pioneering work in hypotensive anaesthesia.This is the technique of lowering blood pressure during surgery, making operations safer and more rapid, and enabling more complicated surgery while controlling blood loss from the patient.In 1948-9 the pharmacologists Paton and Zaimis first described a range of new drugs, the methonium compounds, some of which could lower blood pressure.Hale Enderby saw that this fall in blood pressure could be used to lessen bleeding during surgery-the snag was measuring the low blood pressures.Early methods of measurement relied on using a mercury column, but the Korotkov sounds become inaudible below 60 mm Hg systolic.The pulse also becomes impalpable at that pressure.However, this was the level of blood pressure needed to reduce bleeding significantly.Hale Enderby introduced into anaesthesia the oscillometer, an older and largely forgotten method of blood pressure measurement but one that proved capable of measuring accurately these low pressures.He was also responsible for introducing the "anti-trendelenburg" or head-up tilt of the operating table to assist in the lowering of blood pressure.George Edward Hale Enderby was born in Boston, Lincolnshire.At the start of the second world war he joined the emergency medical service after being turned down for active military service because of a duodenal ulcer.He worked initially at Guy's Hospital and then at Pembury Hospital, Kent, to which many of the Guy's facilities were moved after the hospital was bombed at the start of the war.It was there that he was asked to move into anaesthesia.He organised most of his training himself by reading and visiting notable anaesthetists of the day.
Why Do Elderly Migrate From High Altitudes?
Authors: Mark J. Popp
Journal: JAMA (1985)

<h3>To the Editor.—</h3> I read with great interest the article entitled "Migration of the Elderly From High Altitudes in Colorado" in the June 7 issue of<i>JAMA</i>.<sup>1</sup>I certainly can't disagree with the conclusion that elderly people do migrate from high altitudes to lower altitudes. What really surprised me, however, was the fact that the reason for the migration was unknown. The large survey size leads me to believe that the researchers may have had difficulty drawing their conclusions. They state that four times as many elderly persons left high altitudes for reasons of poor health as left for any other reason. Climate was the only other frequently cited reason. Perhaps if the researchers had asked different questions they would have found that climate had more to do with the heart and lung disease they encountered than altitude. I migrated from a low-elevation of about 200 m in the
PLASMA AND PLATELET EXPRESSION OF MIR-30E-3P IS SIGNIFICANTLY GREATER IN STRESS CARDIOMYOPATHY COMPARED TO ACUTE MYOCARDIAL INFARCTION
Authors: Timothy P. Fitzgibbons, Jeanine Ward, Gerard P. Aurigemma, Kahraman Tanriverdi, Jane E. Freedman, David D. McManus
Journal: Journal of the American College of Cardiology (2013)