tbuckley/cabot-search huggingface dataset:
Immunomodulating anti-cancer chemotherapy based on HPMA conjugates with pH-controlled release of doxorubicin.
Authors: Tomas Mrkvan, Tomas Etrych, Petr Chytil, Milada Sirova, Jiri Strohalm, Dana Plocova, Karel Ulbrich, Blanka Rihova
Journal: Cancer Research (2006)

5577   Chemotherapy is an established modality in cancer treatment and the range of anti-tumor agents is fairly broad. However, most clinically used drugs cause severe side-effects to the patients. Therefore, a search for highly specific anti-cancer agents possessing decreased adverse toxicity is currently one of major issues in anti-cancer research. During last decades, a group of novel therapeutics - polymeric macromolecular prodrugs - was developed and found to comply with the criteria of reduced non-specific toxicity and tumor specificity. Moreover, the specificity of these prodrugs was shown to be further enhanced if coupled to polyclonal or monoclonal antibodies or other tumor-recognizing molecules. Among these macromolecular systems, especially polymeric conjugates of  N -(2-hydroxypropyl)methacrylamide (HPMA) copolymers and doxorubicin proved to be highly efficient in targeted killing of tumor cells. Several types of HPMA based prodrugs were designed with the aim to additionally improve their therapeutic effect. Recently, conjugates with pH-controlled release of the drug proved to be extremely effective in killing tumor cells  in vitro . These prodrugs are also highly potent in managing experimental cancer models  in vivo , i.e. HPMA-based therapeutics are able to induce complete and long lasting remission of established tumor. More importantly, we have repeatedly documented that the cured animals do not develop the disease if re-transplanted with a lethal dose of original tumor cells even some one hundred days after the onset of the therapy. As this anti-tumor resistance can be transferred with splenocytes of cured donors to naive recipients, we can conclude that polymeric conjugates are capable of triggering the onset of effective specific anti-tumor immune response in treated animals. To find whether such an immune response is effective also in an early phase of the therapy, we transplanted treated mice with a challenge tumor cells while the original tumor was still present, however, when the drug is not detectable in the bloodstream anymore. As the challenge cells were prevented from establishing tumor, it seems that those cells had to be managed by immune system since there was no drug available to account for the effect. Therapy with HPMA-based conjugates is highly efficient in managing growing tumors and, moreover, triggers effective anti-tumor immunity early during the course of the treatment. Activated immune system, in addition to direct cytotoxic effect the drug, is responsible for the eradication of established tumor. In sum, HPMA based conjugates generally and particularly those with pH-controlled release of the drug seem to be very promising novel agents for efficient anti-cancer treatment. Acknowledgement: The research was supported by GACR (GACR 310/03/H147, GACR 305/02/1425), IGA AVCR (A 4050201) and by Institutional Research Concept (AV0Z5020903).
Abstract 35: Transcriptome-wide Association Study of Circulating Lipid Levels
Authors: Brian H Chen, Claudia Schurmann, Marjolein J Peters, Liliane Pfeiffer, Katharina Schramm, Luke C Pilling, Roby Joehanes, Lita Freeman, Hanieh Yaghootkar, Tonu Esko, L. Adrienne Cupples, Harald Grallert, Andrew D Johnson, Sekar Kathiresan, Peter J Munson, Eva Reischl, Melanie Waldenberger, Saixia Ying, David Melzer, Luigi Ferrucci, Holger Prokisch, Christian Herder, Aaron Isaacs, Daniel Levy, Alexander Teumer
Journal: Circulation (2014)

Genome-wide association studies have identified scores of DNA variants that are associated with circulating lipid levels. We conducted a transcriptome-wide association study (TWAS) of triglycerides (TG), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and total cholesterol (TC) using whole blood derived RNA from 1,838 Framingham Heart Study participants using the Affymetrix GeneChip Human Exon 1.0 ST array. External replication was conducted in four separate population-based cohorts (SHIP-TREND, KORA F4, Rotterdam Study, InChianti) totaling 3,244 individuals assayed using the Illumina HumanHT-12 Expression BeadChip array. Individuals taking lipid-lowering medications were excluded from analysis. Models were adjusted for age, sex, blood cell counts, and technical covariates (e.g., batch). Using a stringent transcriptome-wide FDR of 0.05 in both discovery and replication results, there were 119 significant transcript associations for TG; 57 for HDL-C; 1 for LDL-C; and 3 for TC. Expression levels of HDC and CPA3 genes were the two strongest associations with all 4 lipid traits in both discovery and replication cohorts. Known lipid pathway gene MYLIP was inversely associated with triglycerides (replication P=6.4x10-45) and directly associated with HDL-C levels (replication P =3.5x10-26). ABCA1 was also directly associated with triglyceride levels (replication P =9.4x10-50). In summary, through TWAS we identified many known and novel genes whose expression levels in whole blood were associated with circulating lipid levels. We believe that TWAS may serve as a useful method for identifying novel therapeutic targets. However, further studies are needed to elucidate the role that these genes may play in regulating circulating lipid levels or mediating the effect of lipids on atherosclerotic cardiovascular diseases.
A Decent Proposal: Ethical Review of Clinical Research, by D Evans, M Evans
Authors: S. Bewley
Journal: BMJ (1997)

D Evans, M Evans / John Wiley and Sons, £24.95, pp 230 / ISBN 0471 96334 8

All of us like to think that we practise to high ethical standards and that these standards carry over to our research activities. I am not alone in finding the review process of research ethics committees a tiresome hurdle, and I thank goodness that I have not been invited to sit on one. And the BMJ wanted me to review a whole book? Well, it was a good read and enlightening about the fundamental importance of ethical review. The authors know their subject thoroughly from both a theoretical and practical background, and have peppered the test on virtually every page with light hearted quotations just in case you might consider putting the book down to have a cup of tea.

Starting with some history of research ethics committees, they ask whether it should be a societal obligation to take part in research (like paying tax). Our Western liberal view is that the research …
Non-coding RNA as functional player and molecular marker in lung cancer
Authors: Maria Polycarpou-Schwarz, Tony Gutschner, Stefanie Grund, Arne Warth, Heike Zabeck, Catherina Hildenbrand, Marion Baas, Michael Meister, Thomas Muley, Peter Schirmacher, Hans Hoffmann, Philipp Schnabel, Sven Diederichs
Journal: European Respiratory Journal (2011)

Previous research has almost exclusively focused on protein-coding genes as functional players in cancer as well as diagnostic or prognostic molecular markers. However, it is now evident, that the human genome contains many more functionally important and clinically informative entities: the non-coding RNAs (ncRNA). To assess the expression landscape of this new class of molecules, we have profiled the expression of 17000 non-coding RNAs in comparison to 22000 protein-coding mRNAs in early stages of lung adenocarcinoma and matched non-malignant lung tissue. These studies revealed molecular signatures associated with tumorigenesis (tumor vs. normal; diagnostic value), with histological subtypes (acinar vs. solid) as well as with the outcome and metastasis development (prognostic value).  Eight novel, differentially expressed transcripts named “Lung Cancer intergenic RNA” (LuCaiR1 - LuCaiR8) were validated and selected for functional characterization, for which we have implemented several technologies. To identify the molecular RNA-protein-networks in which the ncRNAs could function, we use RNA affinity purification and mass spectrometry. To study loss-of-function phenotypes in human lung cancer cells, we have developed a novel technique to create functional knockouts of ncRNAs in human lung cancer cell lines using Zinc Finger Nucleases. This strategy allows the specific and stable silencing of the targeted ncRNA without off-target effects for functional studies. Our research uncovers the functions at the cellular and molecular level of the differentially regulated ncRNAs as well as their clinical importance as diagnostic and prognostic markers.
Classification of Psychiatric Disorders—Reply
Authors: Paul R. McHugh
Journal: JAMA (2005)

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
The Use of F&lt;sub&gt;1&lt;/sub&gt; Hybrid and Backeross Generations to Reveal New and/or Uncommon Tumor Types&lt;xref ref-type="fn" rid="fn1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: Margaret M. Dickie
Journal: JNCI Journal of the National Cancer Institute (1954)

The Use of F1 Hybrid and Backeross Generations to Reveal New and/or Uncommon Tumor Types Get access Margaret M. Dickie Margaret M. Dickie Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 791–799, https://doi.org/10.1093/jnci/15.3.791 Published: 01 December 1954
Fluctuating postdexamethasone cortisol levels in a patient with melancholia
Authors: A J Rothschild, A F Schatzberg
Journal: American Journal of Psychiatry (1982)

This case report illustrates a patient’sfluctuating pattern of response to the dexamethasone suppression test (DST) during a course of treatment for major depression. The authors found that normalization of the DST during treatment may be quickly followed by return to nonsuppression and clinical relapse.
Abstract 16805: Hepatic HNF1α Knockdown Reduces Circulating PCSK9 Levels and Increases Liver LDL Receptor Abundance in Mice
Authors: Vikram R Shende, Amar B Singh, Bin Dong, Jingwen Liu
Journal: Circulation (2014)

Circulating PCSK9, which is secreted by the liver, binds to hepatic LDL receptor (LDLR) and causes its lysosomal degradation. Thus PCSK9 inhibits LDL-cholesterol uptake and has hence become an important therapeutic target for the treatment of hypercholesterolemia. Previous in vitro studies have implicated the transcription factors hepatocyte nuclear factor 1 alpha and beta (HNF1α & HNF1β) as positive regulators of PCSK9 transcription based on their binding to the HNF1 binding site on PCSK9 promoter. However, in vivo evidence for their individual roles in the regulation of PCSK9 expression in liver tissue is largely lacking. In this current study, we utilized adenoviral shRNA delivery vectors to generate liver specific knockdown of HNF1α or HNF1β. We first validated the shRNA viral constructs (Ad-shHNF1α and Ad-shHNF1β) in vitro and observed that knockdown of HNF1α but not of HNF1β reduced PCSK9 mRNA expression by ~50% in cultured HepG2 cells. The decrease in PCSK9 was also associated with increased LDLR p...
Association between 2009 seasonal influenza vaccine and influenza-like illness during the 2009 pandemic: preliminary results of a large household transmission study in Western Australia
Authors: D Carcione, C Giele, L S Goggin, K S Kwan, D W Smith, G K Dowse, D B Mak, P Effler
Journal: Eurosurveillance (2010)

Binary file ES_Abstracts_Final_ECDC.txt matches
Caspases Mediate Retinoic Acid–Induced Degradation of the Acute Promyelocytic Leukemia PML/RARα Fusion Protein
Authors: Clara Nervi, Fabiana F. Ferrara, Mirco Fanelli, Maria Rita Rippo, Barbara Tomassini, Pier Francesco Ferrucci, Martin Ruthardt, Vania Gelmetti, Carlo Gambacorti-Passerini, Daniela Diverio, Francesco Grignani, Pier Giuseppe Pelicci, Roberto Testi
Journal: Blood (1998)
777. Inactivated Adenoviral Vectors with a Conditional Infectivity
Authors: Mark W. Pandori, Takeshi Sano
Journal: Molecular Therapy (2004)

Safe and effective use of viral vectors for gene therapeutics requires versatile control over their delivery to target sites in human subjects. We have developed a strategy for the creation of adenoviral vectors that possess conditional infectivity. Adenoviral vectors were inactivated chemically such that they had little ability to infect cells. However, when such chemically inactivated adenoviral vectors were conjugated to the surfaces of certain microbeads (nanocarriers), which were provided with the ability to associate stably with the surfaces of cells, the infectivity of these adenoviral vectors was restored. For certain target cell lines, the infectivity of such adenovirus-microbead conjugates was even higher than that of free, unmodified adenoviral vectors. An advantage of the chemical inactivation of viral infectivity is that any adenoviral particles, which become free from the microbeads, should be non-infectious. As a result, these chemically inactivated adenoviral vectors have an infectivity that is conditional: They can only infect cells, to which their microbead conjugates come into stable contact. These chemically inactivated adenoviral vectors with a conditional infectivity should be very useful for the development of efficient, versatile targeting strategies for adenoviral vectors.
Abstract 13054: STEMI Occurring in Hospitalized Patients is Associated with Less Aggressive Care and Higher Mortality than Outpatient STEMI
Authors: Jerome J Federspiel, Xuming Dai, Sally C Stearns, Sidney C Smith, Prashant Kaul, Michael Yeung, Hadi Beyhaghi, Lei Zhou, George A Stouffer
Journal: Circulation (2013)
Api m 10, a genuine A. mellifera venom allergen, is clinically relevant but underrepresented in therapeutic extracts
Authors: S. Blank, H. Seismann, Y. Michel, M. McIntyre, L. Cifuentes, I. Braren, T. Grunwald, U. Darsow, J. Ring, R. Bredehorst, M. Ollert, E. Spillner
Journal: Allergy (2011)

Generalized systemic reactions to stinging hymenoptera venom constitute a potentially fatal condition in venom-allergic individuals. Hence, the identification and characterization of all allergens is imperative for improvement of diagnosis and design of effective immunotherapeutic approaches. Our aim was the immunochemical characterization of the carbohydrate-rich protein Api m 10, an Apis mellifera venom component and putative allergen, with focus on the relevance of glycosylation. Furthermore, the presence of Api m 10 in honeybee venom (HBV) and licensed venom immunotherapy preparations was addressed.Api m 10 was produced as soluble, aglycosylated protein in Escherichia coli and as differentially glycosylated protein providing a varying degree of fucosylation in insect cells. IgE reactivity and basophil activation of allergic patients were analyzed. For detection of Api m 10 in different venom preparations, a monoclonal human IgE antibody was generated.Both, the aglycosylated and the glycosylated variant of Api m 10 devoid of cross-reactive carbohydrate determinants (CCD), exhibited IgE reactivity with approximately 50% of HBV-sensitized patients. A corresponding reactivity could be documented for the activation of basophils. Although the detection of the native protein in crude HBV suggested content comparable to other relevant allergens, three therapeutical HBV extracts lacked detectable amounts of this component.Api m 10 is a genuine allergen of A. mellifera venom with IgE sensitizing potential in a significant fraction of allergic patients independent of CCD reactivity. Thus, Api m 10 could become a key element for component-resolved diagnostic tests and improved immunotherapeutic approaches in hymenoptera venom allergy.
Brave new epigenomes: the dawn of epigenetic engineering
Authors: Anna Köferle, Stefan H. Stricker, Stephan Beck
Journal: Genome Medicine (2015)

DNA sequence of choice.Alternatively, the chromatin modifier is fused to a catalytically inactive version of the Cas9 protein (dCas9), which is targeted via a separate, synthetic RNA molecule known as the guide RNA (gRNA).The base sequence of the gRNA determines the DNA-binding specificity of the fusion protein.A range of chromatin modifiers have already been engineered in this way, representing the first components of an epigenetic 'toolbox' (Table 1).These constructs can now be used as tools to address some fundamental questions concerning the function of individual chromatin marks.
Hemostasis and Thrombosis: Basic Principles and Clinical Practice.
Authors: Robert W. Colman
Journal: Annals of Internal Medicine (1988)

PART I - BASIC PRINCIPLES OF HEMOSTASIS AND THROMBOSIS SECTION A - COAGULATION AND ITS REGULATION SECTION B - FIBRINOLYSIS AND ITS REGULATION 285 SECTION C - PLATELET STRUCTURE AND FUNCTION SECTION D - VASCULAR BIOLOGY, EMBRYOGENESIS, DEVELOPMENT, AND DISORDERS PART II - CLINICAL APPLICATIONS SECTION A - INHERITED HEMORRHAGIC DISORDERS SECTION B - ACQUIRED HEMORRHAGIC DISORDERS SECTION C - THERAPY OF BLEEDING DISORDERS SECTION D - VENOUS THROMBOEMBOLIC DISORDERS SECTION E - CARDIOVASCULARTHROMBOTIC DISEASES SECTION F - COMPLEX THROMBOHEMORRHAGIC DISORDERS SECTION G - THERAPY, NEW DIRECTIONS, AND COMPLICATIONS IN THROMBOTIC DISORDERS
CORONARY SCLEROSIS AND PULMONARY HYPERTENSION
Authors: E H DRAKE
Journal: Annals of Internal Medicine (1951)

Article1 September 1951CORONARY SCLEROSIS AND PULMONARY HYPERTENSIONEUGENE H. DRAKE, M.D., F.A.C.P.EUGENE H. DRAKE, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-35-3-600 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe cardiac effects of marked deformity of the chest, of chronic bronchitis and of emphysema have been known for many years. New interest in the interrelationship of diseases of the lungs and heart followed the clinical description of acute cor pulmonale and the observed frequency of pulmonary infarction. Cardiac catheterization has recently shown that the postulated pulmonary hypertension actually exists in those diseases of the lungs which bring strain upon the right side of the heart.1Chronic pulmonary heart disease is not uncommon. Spain and Handler2have described the findings at autopsy in 60 cases of chronic cor pulmonale unaccompanied...Bibliography1. DowHealeyWittenbergerEppingerLevine JWRFJLECHD: The large pulmonary artery, Proc. New England Heart A. 3-5, 1948-1949. Google Scholar2. SpainHandler DMBJ: Chronic cor pulmonale, Arch. Int. Med. 77: 37-65 (Jan.) 1946. CrossrefGoogle Scholar3. MackGrossmanKatz IMLN: Effect of pulmonary vascular congestion on distensibility of the lungs, Am. J. Physiol. 105: 654-660 (Oct.) 1947. CrossrefGoogle Scholar4. Parin VV: The role of pulmonary vessels in reflex control of blood circulation, Am. J. M. Sc. 214: 107 (Aug.) 1947. Google Scholar5. MotleyCournandWerkaHimmelsteinDresdale HLAAAD: Influence of short periods of induced acute anoxia on pulmonary artery pressure in man, Am. J. Physiol. 150: 315-320 (Aug.) 1947. CrossrefMedlineGoogle Scholar6. Cournand A: Recent observations on dynamics of pulmonary circulation, Bull. New York Acad. Med. 23: 27-50 (Jan.) 1947. MedlineGoogle Scholar7. Hamilton KA: Pulmonary disease manifestations of ankylosing spondylarthritis, Ann. Int. Med. 31: 216-228 (Aug.) 1949. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Portland, Maine*Presented at the Regional Meeting of the American College of Physicians in Montreal, September 23, 1949.Received for publication April 17, 1950. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCORONARY HEART DISEASE IN THE PRESENCE OF PULMONARY DISEASE 1 September 1951Volume 35, Issue 3Page: 600-607KeywordsCardiovascular therapyCatheterizationChronic bronchitisEmphysemaHeart diseasesInfarctionLungsPulmonary diseasesPulmonary hypertensionThorax ePublished: 1 December 2008 Issue Published: 1 September 1951 PDF downloadLoading ...
Clinical Pharmacology: Basic Principles in Therapeutics.
Authors: Kenneth L. Melmon, Howard F. Morrelli
Journal: Annals of Internal Medicine (1972)

This book by some 22 authors, and weighing 1-36 kg, is a significant phenomenon by many standards.The problem is to guess to whom it will prove useful or informative.Because the problem cannot be solved by three random glances, this reviewer decided to write his review after using the book in six actual clinical problems, realising well that it was in fact largely written for medical undergraduates.The book's interest can only be seen against some historical background.Good research in clinical pharmacology has been going on for a very long time, in departments of medicine and pharmacology, but the subject has only recently begun to crystallise explicitly as an applied science between these disciplines.The conditions needed for its incorporation seem to have been a transcendence of the opportunities of affluence over traditional departmental structures.Wherever this has happened, particularly in the USA, or
Do men who have sex with men use serosorting with casual partners in France? Results of a nationwide survey (ANRS-EN17-Presse Gay 2004)
Authors: A Velter, A Bouyssou-Michel, A Arnaud, C Semaille
Journal: Eurosurveillance (2009)

We examined whether men who have sex with men (MSM) in France have adopted serosorting with their casual partners, serosorting being one strategy to reduce the risk of HIV transmission. We expected to see the same predictors of this practice with casual partners in France as in other similar MSM communities (HIV-seropositive, Internet dating). Data from a cross-sectional survey was used, based on a self-administered questionnaire conducted among readers of the gay press and users of gay websites in 2004. The study population consisted of MSM who reported their HIV status, as well as the practice of unprotected anal intercourse (UAI) with a casual partner at least once during the previous 12 months. Among 881 respondents included in the analysis, 195 (22%) had practiced serosorting: 14% among HIV-seropositive men and 26% among HIV-seronegative men. Serosorting was independently associated with the use of cruising venues (AOR 0.28, p=0.001) and Internet dating (AOR 2.16, p=0.051) among HIV-seropositive men, whereas it was independently associated with the use of cruising venues (AOR 0.59, p=0.013) and the fact of having less partners (AOR 1.50, p=0.046) among HIV-seronegative men. Serosorting requires an up-to-date knowledge of HIV serostatus for MSM and their UAI casual partners, and does not prevent from acquiring other sexually transmitted infections. Prevention campaigns are needed to underline the risks associated with serosorting.