tbuckley/cabot-search huggingface dataset:
531. Complexes of DNA-Cationic Liposomes with Baculovirus GP64 Envelope Fusion Protein Vesicles Demonstrate Enhanced Transfection Efficiency
Authors: Ghiabe H. Guibinga, Shaochun Song, Jeanne Loring, Theodore Friedmann
Journal: Molecular Therapy (2006)

The need for efficient and safe gene transfer reagents has led to the growing interest in a class of hybrid vectors comprising both viral and non-viral components can be associated. We have examined the transfection efficiency of DOTAP-based lipoplexes together with partially purified vesicles of the baculovirus GP64 envelope glycoprotein eihter alone or as a fusion protein of GP64 with the complement-inactivating decay accelerating factor (DAF, CD55). The addition of GP64 vesicles to lipoplexes expressing luciferase gene enhances the transient transfection efficiency in several target cells in tissue culture by up to approximately 15-fold, as measured by luciferase activity. The enhanced transfection is markedly inhibited by the addition of a GP64-neutralizing antibody. GP64- mediated enhancement of DOTAP-based lipoplexes is associated with physical interaction between the DNA-liposomes with the GP64/ fusion protein, as assayed as by sucrose density gradient centrifugation. These results complement our previous demonstrations of enhanced transfection efficiency of complexes of plasmids or lipoplexes with the VSV-G glycoprotein and suggest that several kinds of viral envelope proteins facilitate the attachment, cell entry and gene transfer efficiencies of nanoparticle complexes.
Exploiting the Cold-Urticaria Model
Authors: Kenneth P. Mathews
Journal: New England Journal of Medicine (1981)

Although cold urticaria is sometimes scarcely more than a minor annoyance, there is substantial disability in more severe cases, and occasionally it may result in death from swimming in cold water. In addition to the clinical importance of cold urticaria, however, there is the possibility that progress in understanding this intriguing problem may provide insights into the broader and common problem of chronic idiopathic urticaria, which is frustrating to patients and physicians alike. Cold urticaria is one of the "physical allergies" that can sometimes be passively transferred by serum to normal skin by the Prausnitz–Kustner technique, with the sensitized sites . . .
Evangelists and Snails
Authors: Jerome L. Sullivan
Journal: Annals of Internal Medicine (1996)

Letters15 December 1996Evangelists and SnailsJerome L. Sullivan, MD, PhDJerome L. Sullivan, MD, PhDVeterans Affairs Medical Center, Charleston, SC 29401.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-12-199612150-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:It is no longer appropriate to describe the two opposing papers on the cholesterol debate [1, 2] as “classic snail and evangelist documents” [3]. “Evangelist” is a metaphor for one who demands public health action based on best judgment, whereas a “snail” requires more rigorous proof [3]. Two decades ago, a recommendation to lower cholesterol levels might have been justified on the basis of plausible interpretations of the available data. In the face of imperfect knowledge and incomplete agreement, physicians have a duty to act for patients' interests according to their best medical judgment. However, evangelism for ...References1. Garber AM, Browner WS, Hulley SB. Cholesterol screening in asymptomatic adults, revisited. Ann Intern Med. 1996; 124:518-31. Google Scholar2. LaRosa JC. Cholesterol agonistics. Ann Intern Med. 1996; 124:505-8. Google Scholar3. Davidoff F. Evangelists and snails redux: the case of cholesterol screening [Editorial]. Ann Intern Med. 1996; 124:513-4. Google Scholar Author, Article, and Disclosure InformationAuthors: Jerome L. Sullivan, MD, PhDAffiliations: Veterans Affairs Medical Center, Charleston, SC 29401. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 1996Volume 125, Issue 12Page: 1011KeywordsCardiovascular therapyCholesterolClinical trialsExtrapolationPrevention, policy, and public healthStatins ePublished: 15 August 2000 Issue Published: 15 December 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Understanding the Mechanisms Behind Trastuzumab Therapy for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Neil L. Spector, Kimberly L. Blackwell
Journal: Journal of Clinical Oncology (2009)

Targeted therapy with the humanized monoclonal antibody trastuzumab has become a mainstay for human epidermal growth factor receptor 2 (HER2) -positive breast cancer (BC). The mechanisms of action of trastuzumab have not been fully elucidated, and data available to date are reviewed here. The impact of the mechanisms of action on clinical benefit also is discussed.An extensive literature review of trastuzumab and proposed mechanisms of action was performed.At least five potential extracellular and intracellular antitumor mechanisms of trastuzumab have been identified in the preclinical setting. These include activation of antibody-dependent cellular cytotoxicity, inhibition of extracellular domain cleavage, abrogation of intracellular signaling, reduction of angiogenesis, and decreased DNA repair. These effects lead to tumor cell stasis and/or death. Clinical benefit from trastuzumab-based therapy in both early and advanced BC has been demonstrated. The benefit of trastuzumab use beyond progression has also been shown, which indicates the need for continuous suppression of the HER2 pathway. Targeting both HER2, with various approaches, and other pathways may enhance the clinical benefit observed with trastuzumab and overcome potential resistance. Novel combinations include pertuzumab (a HER2 dimerization inhibitor), lapatinib (a HER1/HER2 tyrosine kinase inhibitor), bevacizumab (an antiangiogenic agent), tanespimycin (a heat shock protein inhibitor), antiestrogen therapies, and an antibody-drug conjugate (trastuzumab-DM1).Trastuzumab is the foundation of care for patients with HER2-positive BC. Emerging data from studies of other targeted agents may provide alternative treatment combinations to maximize the clinical benefit from trastuzumab and prevent or delay resistance. The continued development of trastuzumab highlights promising treatment approaches for the future.
Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study
Authors: Heiko Becker, Guido Marcucci, Kati Maharry, Michael D. Radmacher, Krzysztof Mrózek, Dean Margeson, Susan P. Whitman, Peter Paschka, Kelsi B. Holland, Sebastian Schwind, Yue-Zhong Wu, Bayard L. Powell, Thomas H. Carter, Jonathan E. Kolitz, Meir Wetzler, Andrew J. Carroll, Maria R. Baer, Joseph O. Moore, Michael A. Caligiuri, Richard A. Larson, Clara D. Bloomfield
Journal: Blood (2010)
Elective ventilation of potential organ donors
Authors: J Fabre
Journal: BMJ (1995)

outcomes study had a range of purposes.The two methodologies have a complementary finction and should not be promoted as polar opposites.Each methodology, however, is grounded in a distinct paradigm; in particular, qualitative methods are more concerned with developing adequate conceptual frameworks than with establishing generalisability.We suggest that, although it is common, it is inappropriate to judge qualitative methods from a quantitative standpoint, as Bisset and Chesson are attempting to do.
Pseudogout with Low Values of Alkaline Phosphatase in the Synovial Fluid
Authors: MICHAEL YARON
Journal: Annals of Internal Medicine (1970)

Two cases of pseudogout are discussed. In the synovial fluid of the affected joints persistent low alkaline phosphatase activity was found. Such low synovial fluid levels and such a discrepancy between synovial fluid and serum values of alkaline phosphatase could not be detected in patients with other diseases. Alkaline phosphatase levels in synovial fluids from different patients were not proportional to the respective total protein and globulin values. Low activity of alkaline phosphatase in the synovial fluid in pseudogout may be related to local deposition of calcium pyrophosphate crystals.
Specialized functions of MHC class I molecules. I. An N-formyl peptide receptor is required for construction of the class I antigen Mta.
Authors: S M Shawar, R G Cook, J R Rodgers, R R Rich
Journal: The Journal of Experimental Medicine (1990)

Maternally transmitted factor (Mtf) is a mitochondrial gene that controls the antigenic polymorphism of the MHC class I maternally transmitted antigen (Mta). Synthetic peptides from the NH2 terminus of the mitochondrially encoded NADH dehydrogenase subunit 1 (ND1) mimic Mtf peptide activity in an allele-specific manner. We show that the minimal ND1-alpha peptide length recognized by Mtaa-specific polyclonal CTLs was between 8 and 12 amino acids, while some Mtaa-specific CTL clones recognized a six amino acid peptide. The N-formyl group at the NH2 terminus of ND1 was essential for Mta activity. Competition experiments using N-substituted ND1-alpha peptides showed that an N-formyl peptide receptor on the target cell, which differs from the chemotactic peptide receptor, was required for Mta expression. The specificity of this receptor can account for the distinct immune restriction of Mta in which Mtf peptides are uniquely restricted by Hmt. It is possible that the Hmt gene product is the N-formyl peptide receptor itself and that it represents a class I antigen presentation molecule specialized for binding, transport, and immune presentation of N-formyl-peptide antigens of mitochondrial and prokaryotic origin.
Influence of a Diet High in Unsaturated Fat upon Composition of Arterial Tissue and Atheromata in Man
Authors: SEYMOUR DAYTON, SAM HASHIMOTO, MORTON LEE PEARCE
Journal: Circulation (1965)

Detailed chemical analyses have been carried out on aorta, and on coronary and aortic atheromata, of men who died during a study of prolonged use of diets rich in unsaturated fat and of control subjects. Concentrations of total aortic lipid and of total aortic calcium were not significantly different for the two groups of subjects. Concentrations of cholesterol and cholesterol esters, triglyceride, and phosphatide showed no difference between the two groups in analyses of aorta, uncomplicated aortic atheromata, complicated aortic atheromata, and coronary atheromata. Coronary atheroma lipid contained substantially more triglyceride than did aortic atheroma lipid, whether derived from complicated or uncomplicated plaques. Atheroma triglyceride in experimental subjects contained more linoleic acid than in control subjects, in all types of plaques. Lesser but significant increases in linoleic acid were seen in cholesterol ester and phosphatide of coronary atheromata and complicated aortic atheromata. In the case of uncomplicated aortic atheroma, changes in linoleic acid of cholesterol ester and phosphatide were smaller and not significant. In both groups of subjects, coronary atheroma contained more cholesteryl oleate and less linoleate than did aortic atheroma. Linoleic acid contents of atheroma lipid fractions were positively correlated with the linoleic acid figures for corresponding fractions of the most recent antemortem serum samples. Ratio of linoleic acid in an atheroma lipid fraction to the linoleic acid content of the corresponding serum fraction was, in most cases, constant after the time of the first sample, obtained after 495 days on experimental diet. It is postulated that this ratio constitutes an estimate of the fraction of atheroma fatty acid derived from plasma. In cholesterol ester and triglyceride, the ratio was about 0.65 in experimental subjects, higher in subjects on the control diet. The ratio for phosphatide was about 0.5 in both groups of subjects.
T lymphocytes and silica-induced pulmonary inflammation and fibrosis in mice.
Authors: N. Suzuki, K. Ohta, T. Horiuchi, H. Takizawa, T. Ueda, M. Kuwabara, J. Shiga, K. Ito
Journal: Thorax (1996)

BACKGROUND: Silica-induced pulmonary inflammation and fibrosis in animals provides a good model for chronic pulmonary inflammation and fibrosis. Although lymphocytes are implicated in the pathogenesis of pulmonary fibrosis, experimental models using silica-treated athymic nude mice have not been successful in showing the fibrogenic mechanism regulated by T cells. The aim of this study was to re-evaluate the role of T lymphocytes in the development of silicosis by comparing the response to silica administration of nude athymic mutants with that of euthymic animals. METHODS: Suspensions of silica particles were transnasally administered to nude athymic mice (Balb/c nu/nu) as well as to their euthymic littermates (Balb/c nu/+). The degree of pulmonary inflammation and fibrosis was assessed on days 14, 28, and 56 based upon histological observation, analysis of collagen deposition in the lungs, and analysis of the cellular constituent, protein, and phospholipid content in the bronchoalveolar lavage fluid. RESULTS: Histologically, athymic mice developed less severe interstitial pneumonitis than euthymic mice. In euthymic mice the lung hydroxyproline content increased with time after silica administration from 6.48 (0.38) micrograms hydroxyproline/mg dry lung weight on day 0 to 8.87 (0.41) micrograms/mg on day 56. A gradual increase in lung hydroxyproline content was also observed in athymic mice but the increase was significantly smaller than in euthymic mice (6.63 (0.43) micrograms/mg on day 0, 7.90 (0.19) micrograms/mg on day 56). Administration of silica resulted in an increase in the number of macrophages and neutrophils and in the total protein and phospholipid content of the bronchoalveolar lavage (BAL) fluid in both mouse strains. No significant difference was detected between athymic and euthymic mice in the numbers of macrophages, but the increase in neutrophils in the BAL fluid of athymic mice was significantly smaller than in euthymic mice on days 14 and 56. The total protein and phospholipid content of the BAL fluid from athymic mice was lower than that from euthymic mice. CONCLUSIONS: T lymphocytes appear to be involved in the pathogenesis of silica-induced pneumonitis. Since pulmonary fibrosis develops even in nude athymic mice, T cells do not seem to play a primary part in fibrogenic response but they regulate, at least to some extent, the response of inflammatory cells and fibrogenesis of the lung.
My favourite surgical instrument
Authors: Bisalahalli Muddu
Journal: BMJ (2005)

When I started as a registrar in orthopaedics, one of the first consultants I worked with always used a MacDonald's dissector when things were difficult. His theatre sister remarked to me quietly that he could not operate unless it was on the scrub trolley. The instrument is used to tease soft tissues away from major structures such as nerves, tendons, and arteries as well …
Proposed Embryopathic Relation between Mumps Virus and Primary Endocardial Fibroelastosis
Authors: Joseph W. St. Geme, George R. Noren, Paul Adams
Journal: New England Journal of Medicine (1966)

AN intriguing though poorly understood pathogenetic relation between apparent intrauterine mumps-virus infection and primary endocardia fibroelastosis has evolved from intradermal skin testing of 17 patients with inactivated mumps-virus antigen.1 , 2 The observation of virtually uniform cutaneous delayed hypersensitivity to mumps virus in children with primary endocardial fibroelastosis and the revelation of either gestational parotitis or exposure to clinical mumps in 9 of these patients' mothers has evoked considerable speculation regarding this relation.This paper discusses some of the clinical, epidemiologic, immunologic and virologic aspects of studies that have been pursued in these patients.Clinical MethodsThe criteria sustaining a clinical diagnosis . . .
Effect of streptomycin on wall-stress-induced arrhythmias in the working rat heart
Authors: A Salmon
Journal: Cardiovascular Research (1997)

Objective: To assess whether streptomycin, an inhibitor of mechano-sensitive cation channels, has an effect on arrhythmias induced by an increase of ventricular wall stress in the rat heart. Methods: The isolated working rat heart preparation was used. Arrhythmias were induced by increasing the afterload (i.e., aortic pressure) against which the left ventricle (LV) pumped for 20 s. This led to an increase of LV pressure, stretch of the LV and an increase in LV wall stress. The number of ventricular premature beats induced by each afterload step was compared in the absence and presence of streptomycin, a compound known to block mechano-sensitive cation channels in the heart. Results: Perfusion with 200 μM streptomycin caused a significant reduction in wall-stress-induced arrhythmias. The effect of streptomycin on arrhythmias reached steady-state within 10 min of application. In the presence of streptomycin, arrhythmias elicited by a 40 mmHg afterload increase were reduced to 38% of control. Arrhythmias induced by an 80 mmHg afterload increase were reduced to 61% of control. Complex arrhythmias (ventricular tachycardia) induced by an afterload increase were also reduced in the presence of 200 μM streptomycin. There was no change in inotropic state with streptomycin, as assessed either by cardiac output or by maximum developed LV pressure. Streptomycin 50 μM (a typical therapeutic plasma concentration in patients) had no effect on wall-stress-induced arrhythmias. Conclusions: The results were inconsistent with streptomycin acting by modulating inositol phosphate production, or altering the level of intracellular calcium or inotropic state. The anti-arrhythmic effect of streptomycin appears more consistent with inhibition of mechano-sensitive cation channels, suggesting that these ion channels might be involved in causing wall-stress-induced arrhythmias.
1118 TREATING NAIVE CHRONIC HEPATITIS C PATIENTS WITH DUAL (PEGINTERFERON/RIBAVIRIN, SOC) OR TRIPLE (SOC + PROTEASE INHIBITOR, PI) THERAPY IN HUNGARY. AN APPROACH WITH LIMITED RESOURCES
Authors: B. Hunyady, M. Makara, J. Gervain, G. Horváth, F. Szalay, I. Tornai
Journal: Journal of Hepatology (2012)
Energy Expenditure With Indoor Exercise Equipment
Authors: James M. Rippe
Journal: JAMA (1996)

—In the article by Dr Zeni and colleagues,<sup>1</sup>energy expenditure was compared across 6 different types of indoor exercise equipment with exercise RPE held constant. The authors concluded that "under the conditions of the study," the treadmill was "the optimal indoor exercise machine for enhancing energy expenditure when perceived exertion is used to establish exercise intensity." Although this conclusion may be fair enough, this study has been widely misinterpreted as showing that exercise on a treadmill is superior to exercise on the other 5 types of indoor exercise equipment. In Figures 1 and 2 in the article, it was apparent that both rate of energy expenditure and heart rate were greater at any level of perceived exertion on the treadmill than on any other piece of equipment, and, indeed, the figures were virtually superimposable on each other. However, it is not surprising that individuals expended more energy at each
Anticipating the onset of inflammatory bowel disease
Authors: J F COLOMBEL, D LAHARIE, B GRANDBASTIEN
Journal: Gut (1999)

See article on page 812 

The great interest in identifying susceptibility genes in inflammatory bowel diseases (IBD) has recently triggered the aggregation of family trees throughout Europe and the United States. This has led to a better knowledge of empirical risk and clinical characteristics of familial IBD. One of the most consistent findings in families with Crohn’s disease was early onset in most affected children of an affected parent, with an average difference of 15 years. This may be a more general feature of familial IBD, as shown in this issue by Lee et al (see page 808) who observed a similar time span (16–18 years) between generations in 50 pure Crohn’s disease, 51 pure ulcerative colitis and 36 mixed disease families.

Genetic anticipation has been suggested as a possible explanation for this finding.1 This term denotes a decrease in the age of onset and an increase in severity as a disease is passed through generations.2 Genetic anticipation has been described in monogenic neurological illnesses such as Huntington’s disease, myotonic dystrophy and more recently Friedreich’s ataxia. In these diseases, there …
Measuring later health status of high risk infants: randomised comparison of two simple methods of data collection
Authors: D. Field, E. S Draper, M. J Gompels, C. Green, A. Johnson, D. Shortland, M. Blair, B. Manktelow, C. R Lamming, C. Law
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To test two methods of providing low cost information on the later health status of survivors of neonatal intensive care. <b>Design:</b> Cluster randomised comparison. <b>Setting:</b> Nine hospitals distributed across two UK health regions. Each hospital was randomised to use one of two methods of follow up. <b>Participants:</b> All infants born ≤32 weeks9 gestation during 1997 in the study hospitals. <b>Method:</b> Families were recruited at the time of discharge. In one method of follow up families were asked to complete a questionnaire about their child9s health at the age of 2 years (corrected for gestation). In the other method the children9s progress was followed by clerks in the local community child health department by using sources of routine information. <b>Results:</b> 236 infants were recruited to each method of follow up. Questionnaires were returned by 214 parents (91%; 95% confidence interval 84% to 97%) and 223 clerks (95%; 86% to 100%). Completed questionnaires were returned by 201 parents (85%; 76% to 94%) and 158 clerks (67%; 43% to 91%). Most parents found the forms easy to complete, but some had trouble understanding the concept of “corrected age” and hence when to return the form. Community clerks often had to rely on information that was out of date and difficult to interpret. <b>Conclusion:</b> Neither questionnaires from parents nor routinely collected health data are adequate methods of providing complete follow up data on children who were born preterm and required neonatal intensive care, though both methods show potential. <h3>What is already known on this topic</h3> Outcome of neonatal intensive care should include later health status not just early mortality Although these data are commonly sought, for various reasons no existing routine system currently delivers the information for ≥95% of the population (95% representing the minimum acceptable standard) Running one-off studies to gain later follow up data is difficult and costly <h3>What this study adds</h3> Potentially these data could come from parents but to reach 95% ascertainment perhaps 5-10% of parents would require help and support to provide information Existing data flows may be able to provide the required information if the timing of routine reviews and methods of data recording were harmonised across the United Kingdom The costs attached to introducing such a system seem to be low