tbuckley/cabot-search huggingface dataset:
CD8+ T-cell interaction with HCV replicon cells: Evidence for both cytokine- and cell-mediated antiviral activity
Authors: C Liu
Journal: Hepatology (2003)

The interaction between the host immune response and infected hepatocytes plays a central role in the pathogenesis of hepatitis C virus (HCV). The lack of a suitable animal or in vitro model has hindered our understanding of the host T-cell/HCV interaction. Our aim was to develop an in vitro model to study the mechanisms of HCV-specific T-cell-mediated antiviral and cytolytic function. The HCV replicon was HLA typed and lymphocytes were obtained from an HLA class I-matched subject. CD8+ T cells were expanded with 2 HCV-specific/HLA-restricted peptides for NS3. Lymphocyte preparations were cocultured with HCV replicon (FCA1) and control (Huh7) cells labeled with 51Cr. After a 48-hour incubation, the cells were harvested for RNA extraction. Standard blocking assays were performed in the presence of anti-interferon gamma (IFN-γ), anti-tumor necrosis factor α (TNF-α), and anti-FasL. Cytolytic activity was measured by 51Cr release. HCV replicon cells express homozygous HLA-A11 alleles and present HCV nonstructural proteins. HCV-specific expansion of CD8+ cells led to a 10-fold decrease in HCV replication by Northern blot analysis and 21% specific lysis of FCA1 cells (compared with 2% of control Huh7 cells). Twenty percent of this antiviral activity was independent of T-cell binding, suggesting cytokine-mediated antiviral activity. The CD8+ antiviral effect was markedly reduced by blocking either IFN-γ or FasL but was unaffected by blocking TNF-α. In conclusion, HCV-specific CD8+ cells inhibit viral RNA replication by cytokine-mediated and direct cytolytic effects. This T-cell/HCV subgenomic replicon system represents a model for the investigation of CD8 cell interaction with HCV-infected hepatocytes.
TCT-37 Five-year Clinical Outcomes and Non-invasive Angiographic Imaging Results With Functional Assessment After Bioresorbable Everolimus-eluting Scaffold Implantation in Patients with De Novo Coronary Artery Disease
Authors: Yoshinobu Onuma, Koen Nieman, Mark Webster, Leif Thuesen, Dariusz Dudek, John Ormiston, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2012)
Oxygen therapy. Evaluation of various air-entraining masks
Authors: S. A. Friedman
Journal: JAMA (1974)

Two types of Venturi masks claiming to deliver 24%, 28%, 35%, and 40% oxygen were studied with a new method employing ultrathin, large plastic bags, as well as by conventional methods. There were considerable variations between actual and claimed performance. Some masks delivered oxygen concentrations higher than the designated value. The masks were not truly "Venturi" in design. Their delivered oxygen concentrations vary somewhat depending on the stage of the patient's respiratory cycle. (<i>JAMA</i>228:474-478, 1974)
Consent for Aspirin Trial
Authors: GEORGE L. COHN
Journal: Annals of Internal Medicine (1977)

Letters and Corrections1 July 1977Consent for Aspirin TrialGEORGE L. COHN, M.D., F.A.C.P.GEORGE L. COHN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-87-1-121_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The paper by Drs. Sbarbaro and Bennett in the February issue (Ann Intern Med86:183-185, 1977) is of great interest to clinicians. Their work-up and development of the problem of hepatotoxicity of aspirin is to be commended. However, I am concerned with their use of aspirin in a "cautious, diagnostic, and therapeutic trial" without any record of the patient's consent. It would seem to me that the danger of using aspirin in this clinical trial warranted permission from the patient and an explanation of potential complications. Although this may have been done, these facts were not mentioned... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine and Psychiatry Yale University School of Medicine New Haven, CT 06510 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1977Volume 87, Issue 1Page: 121-121KeywordsAspirinClinical trials Issue Published: 1 July 1977 PDF downloadLoading ...
Symptomatic Osteoporosis in a Man with Hyperprolactinemic Hypogonadism
Authors: JEFFREY A. JACKSON
Journal: Annals of Internal Medicine (1986)

A 66-year-old man presented with height loss, back pain due to an L4 vertebral compression deformity, and marked osteopenia shown by radial photon absorptiometry. The patient had small testes and a long history of infertility and impotence. Plasma testosterone was low (130 ng/dL; normal, 300 to 1000 ng/dL) with marked elevation of serum prolactin (590 ng/mL; normal, 0 to 15 ng/mL). High-resolution computed tomography showed an invasive pituitary macroadenoma with a secondary empty sella turcica. Bone histomorphometry showed low-normal trabecular bone volume with normal formation and resorption indices. The patient was treated with calcium carbonate supplements, testosterone replacement, and bromocriptine mesylate without subsequent progression of the osteoporosis. This first report of hyperprolactinemic hypogonadism in a man who presented with overt osteoporosis shows the importance of evaluating gonadal function in all osteoporotic men.
Monitoring Heparin Therapy
Authors: Robert Raschke
Journal: Annals of Internal Medicine (1994)

Letters15 January 1994Monitoring Heparin TherapyRobert Raschke, MD and Brendan Reilly, MDRobert Raschke, MDGood Smaritan Regional Medical Center; Phoenix, AZ 85006Search for more papers by this author and Brendan Reilly, MDGood Smaritan Regional Medical Center; Phoenix, AZ 85006Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-2-199401150-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We agree with the conclusions of Brill-Edwards and colleagues [1] regarding the establishment of a therapeutic range for heparin. Some institutions, however, might not have the resources to establish a therapeutic activated partial thromboplastin time (aPT) range using heparin levels. Also, care should be taken in adopting one of the reported therapeutic ranges. Specifically, the Dade reagent studied by Brill-Edwards and colleagues (Dade Actin FS; Baxter Diagnostics, Inc., Mississauga, Ontario, Canada) is much more sensitive and will yield a much higher therapeutic range than the reagent most commonly used in the United States (plain Dade Actin) [2]. ...References1. Brill-Edwards P, Ginsberg JS, Johnston M, Hirsh J. Establishing a therapeutic range for heparin therapy. Ann Intern Med. 1993; 119: 104-9. Google Scholar2. College of American Pathologists. 1992 CAP Surveys, Set CG2-A. Northbrook, Illinois. College of American Pathologists; 1992:4-8. Google Scholar3. Hirsh J. Drug therapy: heparin. N Engl J Med. 1991; 324:1565-74. Google Scholar Author, Article, and Disclosure InformationAuthors: Robert Raschke, MD; Brendan Reilly, MDAffiliations: Good Smaritan Regional Medical Center; Phoenix, AZ 85006 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEndovascular treatment of aneurisms: Pre, intra and post operative managementMonitoring Antithrombotic TherapyHeparin: Mechanism of Action, Pharmacokinetics, Dosing Considerations, Monitoring, Efficacy, and Safety 15 January 1994Volume 120, Issue 2Page: 169-170KeywordsBlood plasmaDiagnostic techniquesHeparinLinear regression analysisPartial thromboplastin timeThromboembolism ePublished: 15 August 2000 Issue Published: 15 January 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Promising New Treatments for Cytomegalovirus Retinitis
Authors: Michael A. Polis
Journal: JAMA (1995)

THE SURVIVAL of patients infected with the human immunodeficiency virus (HIV) has improved over the past decade due to the use of antiretroviral therapy and better management of acquired immunodeficiency syndrome (AIDS)—related opportunistic infections. Some opportunistic infections are declining in incidence due to the use of effective chemoprophylaxis. From the period 1985 to 1987 to the period 1991 to 1992, for example, the incidence of<i>Pneumocystis carinii</i>pneumonia (PCP) as an AIDS-defining illness in the United States declined from 60.9% to 42.5% (written communication, Jonathan Kaplan, MD, Centers for Disease Control and Prevention, Atlanta, Ga, March 1995). However, as patients live longer with very low CD4 counts, it is not surprising that the incidence of other opportunistic infections has increased. Over the same time intervals, the incidence of cytomegalovirus (CMV) retinitis has increased from 2.8% of AIDS-defining illnesses to 5.9%.<sup>1</sup><i>Pneumocystis carinii</i>prophylaxis has been responsible for much of
Abstract 1554: Rosiglitazone and Gemcitabine combination therapy reduces immune suppression and modulates T cell populations in pancreatic cancer
Authors: Stephanie K. Bunt, Ashley M. Mohr, Jennifer M. Bailey, Paul M. Grandgenett, Michael A. Hollingsworth
Journal: Cancer Research (2012)

Abstract Pancreatic ductal adenocarcinoma (PDA) is a leading cause of cancer mortality with a dismal 2-5% 5-year survival rate. Monotherapy with Gemcitabine has limited success, highlighting the need for additional therapies that enhance the efficacy of current treatments. We evaluated the combination of Gemcitabine and Rosiglitazone Maleate, an FDA-approved drug for the treatment of type II diabetes, in an immunocompetent transplantable mouse model of pancreatic cancer. Tumor progression, survival and metastases were evaluated in mice with subcutaneous or orthotopic pancreatic tumors treated with Pioglitazone, Rosiglitazone, Gemcitabine or combinations of these. We characterized the impact of high dose Rosiglitazone and Gemcitabine therapy on immune suppressive mediators, including MDSC and T regulatory cells, and on modulation of peripheral and intra-tumoral T cell populations. Combinations of Rosiglitazone and Gemcitabine significantly reduced tumor progression and metastases, enhanced apoptosis, and significantly extended overall survival compared to Gemcitabine alone. Rosiglitazone altered tumor-associated immune suppressive mediators by limiting early MDSC accumulation and intra-tumoral T regulatory cells. Combination therapy with Rosiglitazone and Gemcitabine modulated T cell populations by enhancing circulating CD8+ T cells and intra-tumoral CD4+ and CD8+ T cells while limiting T regulatory cells. The results suggest that Rosiglitazone, in combination with Gemcitabine, decreases immune suppressive mechanisms in immunocompetent animals and provide pre-clinical data in support of combining Rosiglitazone and Gemcitabine as a clinical therapy for pancreatic cancer. 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 1554. doi:1538-7445.AM2012-1554
Gas6 deficiency in recipient mice of allogeneic transplantation alleviates hepatic graft-versus-host disease
Authors: Laurent Burnier, François Saller, Linda Kadi, Anne C. Brisset, Rocco Sugamele, Lucie Baudino, Françoise Bono, Jean-Marc Herbert, Peter Carmeliet, Marc Schapira, Shozo Izui, Anne Angelillo-Scherrer
Journal: Blood (2010)
Hyperhomocysteinemia
Authors: Ingrid M. van Beynum, Jan A. M. Smeitink, Martin den Heijer, Maria T. W. B. te Poele Pothoff, Henk J. Blom
Journal: Circulation (1999)

Moderate hyperhomocysteinemia is a risk factor for arterial vascular disease and venous thrombosis in adults. We performed a case-control study to assess a possible relation between moderate hyperhomocysteinemia and ischemic stroke in Dutch children (age range, 0 to 18 years).We measured plasma total homocysteine levels (tHcy) in 45 patients with ischemic stroke and in 234 controls. Hyperhomocysteinemia was defined as a tHcy above the 95th percentile regression line for the respective age of the controls. Hyperhomocysteinemia was present in 8 (18%) of the 45 patients with ischemic stroke. The odds ratio was 4.4 (95% CI, 1.7 to 11.6).We conclude that moderate hyperhomocysteinemia is a risk factor for ischemic stroke in children.
Venous pressure-volume relation and calf blood flow determined by changes in posture
Authors: G. J. BARENDSEN, J. V. D. BERG
Journal: Cardiovascular Research (1976)

Journal Article Venous pressure-volume relation and calf blood flow determined by changes in posture Get access G. J. BARENDSEN, G. J. BARENDSEN from the Laboratory of Medical Physics, University of Groningen, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar J. VAN DEN BERG J. VAN DEN BERG from the Laboratory of Medical Physics, University of Groningen, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 10, Issue 2, March 1976, Pages 206–213, https://doi.org/10.1093/cvr/10.2.206 Published: 01 March 1976
Presence in Normal Human Testes of a Chorionic-Gonadotropin-like Substance Distinct from Human Luteinizing Hormone
Authors: Glenn D. Braunstein, Joan Rasor, Maclyn E. Wade
Journal: New England Journal of Medicine (1975)

The high rate of human chorionic gonadotropin production by testicular tumors caused us to investigate the possibility that normal human testes contain small amounts of that substance. Extracts of human testes obtained at autopsy demonstrated parallel inhibition curves to the human chorionic gonadotropin standard in a radioimmunoassay specific for the hormone. The immunoreactive material was adsorbed onto concanavalin A, a reaction characteristic of glycoproteins, and was eluted within the chorionic gonadotropin range on Sephadex G-100 column chromatography. Solubilized receptor proteins for the hormone could not be identified in the extracts. The demonstration that the normal human testes contain a glycoprotein similar or identical to human chorionic gonadotropin suggests that the fetal genome responsible for production of the hormone during pregnancy is not completely suppressed in the adult. Excessive productton of this glycoprotein may account for the high levels of human chorionic gonadotropin reported in the serum of patients with germ-cell tumors of the testes.
Bacterial septicaemia with multiple organisms complicating influenzal pneumonia.
Authors: P V Barber, T N Stanbridge
Journal: BMJ (1977)

evoked epilepsy,3 especially in India, and childhood epilepsy may be produced by undressing before being bathed.4Swimming and bathing are known to trigger transient global amnesia.Light shimmering on rippled water may be a factor, particularly in younger patients.5Startle effects during horseplay when swimming is another possibility.5True water-immersion epilepsy ("bath epilepsy")4 5 is rare.Infantile febrile convulsions are a threat, especially in view of the common but mistaken parental practice of putting a child who has had a convulsion into a hot bath (cases 1 and 2; see table).In this study the incidence of epilepsy-induced immersions was 5.4 % (epilepsy-induced fatal immersions 3-6 %).In Maryland 3 4 % of all drownings are due to epileptiform seizures, and in Hawaii 460% of sea drowned victims are epileptics.No epilepsy-induced deaths were reported during swimming in a survey of death during sport in South Africa.Epileptic children should be encouraged to engage in recreation and sport.Competitive swimming, however, may produce somatic stress to the point of exhaustion, which is a trigger for stress epilepsy.Epileptics should never swim or bathe alone (as opposed to showering), and special risks apply to retarded children with epilepsy.With effective supervision, however, epileptic children may swim with confidence.
Effect of a Self-care Book on Physician Visits
Authors: Stephen H. Moore
Journal: JAMA (1980)

A self-care book that guides patients in seeking home care or physician care for 63 medical problems was assessed in three randomly selected groups of families to determine the book's effect on the number of visits to physicians. The first group was given the book and an optional seminar on its use; the second group was identical to the first but each family was promised $50 if their visits to physicians dropped by one third; the third group was a control group (total, 699 families). The book had no significant effect on the number of physician's visits during six- and 12-month study periods even though one half of the families read most or all of the book, and more than one third used it for a specific medical problem. Large-scale distribution of this self-care book therefore did not result in significantly less dependence on physicians for treatment of acute medical problems. (<i>JAMA</i>243:2317-2320, 1980)
Some Characteristics of Ventricular Echoes
Authors: CARLOS MENDEZ, JAOK HAN, P. D. DE JALON, G. K. MOE
Journal: Circulation Research (1965)

Reciprocal responses (ventricular "echoes") were initiated by premature stimuli applied directly to the bundle of His in dog hearts perfused from donor animals. The time relations of the responses in the His bundle and at the atrial margin of the exposed A-V node were studied under a number of conditions. It was found that: 1. The earliest premature response that can be induced in the His bundle is not propagated back to the atrium and does not lead to an echo. 2. There is, in most hearts, a continuous range of H 1 H 2 intervals (the echo "zone") within which reciprocal responses of the His bundle occur. 3. The earliest effective H 2 propagates slowly to the atrium, and the echo returns quickly. 4. The latest effective H 2 responses propagate more quickly to the atria, but return more slowly. 5. The atrium is an essential link in the echo pathway; i.e., the H 2 response must reach and activate the atrium before a return is possible. 6. Direct stimulation of the atrium in advance of the expected arrival of the A 2 response propagated from the His bundle can initiate a response which propagates to the bundle; i.e., two responses can travel in opposite directions on a collision course, yet one of them can complete its journey. 7. The limiting parameter of the return pathway is the refractory period of that portion of the lower node which must fire twice in the echo circuit. 8. The limiting element is not the bundle of His. 9. The limiting element can be discharged by early H 2 responses which fail to reach the atrium. 10. The refractory period of the limiting element is a function of the preceding cycle length. It was also demonstrated that the echo "zone" is shifted to a range of longer H 1 H 2 intervals when the basic driving frequency is increased, or when the vagi are stimulated. Epinephrine shifts the echo zone to a range of briefer H 1 H 2 intervals. It is suggested that echo responses occur when a retrograde impulse is arrested at one site within the node and continues to propagate to the atrium through collateral pathways. If the retrograde propagation time is long enough to permit the recovery of the lower elements of the node, an echo response reaches the His bundle. It was concluded that a self-sustained repetitive circuit may be possible when the round-trip conduction time exceeds the refractory period of the limiting tissue in the node.
Biosynthesis of the third component of complement (C3) in vitro by monocytes from both normal and homozygous C3-deficient humans.
Authors: L P Einstein, P J Hansen, M Ballow, A E Davis, J S Davis, C A Alper, F S Rosen, H R Colten
Journal: Journal of Clinical Investigation (1977)

Human monocytes synthesized the third component of complement (C3) up to 5 wk in vitro. Evidence for net C3 synthesis was based on (a) incorporation of 14C-labeled amino acids into C3 protein, (b) indentity of the allotype of C3 produced in vitro with that of the doner's serum C3, even in the presence of carrier C3 protein of a different allotype; (c) correspondence of electrophoretic mobility, size, and subunit structure of C3 protein produced in vitro with serum C3; (d) inhibition of C3 production with cycloheximide. Monocytes from two unrelated C3-deficient patients were studied under conditions that supported C3 synthesis by normal monocytes. Serum from each of the patients contained less than 1% of the normal C3 concentration, buth their monocytes produced C3 at approximately equal to 25% of the normal rate when studied after 2 wk in vitro. The C3 produced in vitro by monocytes from one of the patients had the molecular weight of normal serum C3 and dissociated appropriately under reducing conditions. Monocytes from C3-deficient patients could not be distinguished from normals on the basis of morphology, rosetting with C3-coated erythrocytes, or rates of C2, and total protein synthesis.
THE INCIDENCE AND TREATMENT OF TRICHOMONAS VAGINALIS IN PREGNANCY
Authors: OSCAR GLASSMAN
Journal: JAMA (1934)

Little attention is given to the vaginal secretion of pregnancy. Though normally greater in amount than in the nonpregnant, it is often considerably increased, contains leukocytes and pathogenic micro-organisms, and results in definite symptoms of varying intensity. The latter condition is frequently dismissed as a normal physiologic change, whereas if the secretion is examined microscopically it will be found in a great majority of instances to be associated with Trichomonas vaginalis. This flagellate is found in about 10 to 40 per cent of pregnant patients and may be found in from 50 to 70 per cent of all patients with leukorrhea. It probably occurs more frequently in the pregnant than in the non-pregnant. One of the reasons may be that the increased female sex hormone in the body enhances its growth. Stein<sup>1</sup>has shown that female sex hormone added to a culture medium causes a much more rapid growth
T-cadherin is critical for adiponectin-mediated cardioprotection in mice
Authors: Martin S. Denzel, Maria-Cecilia Scimia, Philine M. Zumstein, Kenneth Walsh, Pilar Ruiz-Lozano, Barbara Ranscht
Journal: Journal of Clinical Investigation (2010)

The circulating, adipocyte-secreted hormone adiponectin (APN) exerts protective effects on the heart under stress conditions. The receptors binding APN to cardiac tissue, however, have remained elusive. Here, we report that the glycosyl phosphatidylinositol–anchored cell surface glycoprotein T-cadherin (encoded by Cdh13) protects against cardiac stress through its association with APN in mice. We observed extensive colocalization of T-cadherin and APN on cardiomyocytes in vivo. In T-cadherin-deficient mice, APN failed to associate with cardiac tissue, and its levels dramatically increased in the circulation. Pressure overload stress resulted in exacerbated cardiac hypertrophy in T-cadherin-null mice and paralleled corresponding defects in mice lacking APN. During ischemia-reperfusion injury, the absence of T-cadherin increased infarct size similar to that in APN-null mice. Myocardial AMPK is a major downstream protective signaling target of APN. In both cardiac hypertrophy and ischemia-reperfusion models, T-cadherin was necessary for APN-dependent AMPK phosphorylation. In APN-null mice, recombinant adenovirus-expressed APN reduced exaggerated hypertrophy and infarct size and restored AMPK phosphorylation as previously reported. In contrast, rescue was ineffective in mice lacking T-cadherin in addition to APN. These data suggest that T-cadherin protects from stress-induced pathological cardiac remodeling by binding APN and activating its cardioprotective functions.