tbuckley/cabot-search huggingface dataset:
Immunization by Application of DNA Vaccine onto a Skin Area Wherein the Hair Follicles Have Been Induced into Anagen-onset Stage
Authors: Dalia S Shaker, Brian R Sloat, Uyen M Le, Christiane V Löhr, Nijaporn Yanasarn, Kay A Fischer, Zhengrong Cui
Journal: Molecular Therapy (2007)

An attractive approach to immunization is to apply DNA vaccine topically onto the skin. However, it is important to ensure that a strong immune response is induced without disrupting the skin stratum corneum. The hair follicles have been shown to be the major portal of entry for DNA applied onto the skin, and it has been reported that the transfection of hair follicle cells occurs mainly at the onset of a new growing stage of the hair cycle. Using an anthrax protective antigen (PA) protein-encoding plasmid in mice, we demonstrated that the anti-PA immune responses were significantly stronger when the hair follicles in the application area were induced into anagen-onset stage than when in telogen stage. The anti-PA antibodies enabled the immunized mice to survive a lethal dose of anthrax lethal toxin challenge. The enhanced immune responses can be partially attributed to the enhanced antigen gene expression and plasmid DNA uptake in the skin area wherein the hair follicles were induced into anagen-onset stage. Moreover, the moderate dermal inflammation associated with the anagen induction may also have contributed to the enhancement of the resultant immune response. This represents a novel approach to enhancing the immune response induced by a topically applied DNA vaccine.
Radiation Heart Disease.
Authors: Keith E. Cohn
Journal: Annals of Internal Medicine (1967)

s1 May 1967Radiation Heart Disease.Keith E. Cohn, M.D., J. Robert Stewart, M.D., Luis F. Fajardo, M.D., E. William Hancock, M.D., F.A.C.P.Keith E. Cohn, M.D.Search for more papers by this author, J. Robert Stewart, M.D.Search for more papers by this author, Luis F. Fajardo, M.D.Search for more papers by this author, E. William Hancock, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1035_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTwenty-five patients who developed heart disease after radiation therapy to the chest for malignant neoplasm have been studied. Twenty-three patients had pericardial disease, including acute pericarditis (15 cases), chronic pericardial effusion (12 cases), and chronic constrictive pericarditis (10 cases).Pericardial effusion developed during an episode of acute pericarditis in 11 cases, and 6 patients had cardiac tamponade. The pericardial fluid was usually bloody, with a high protein content. Ten patients with acute pericarditis recovered, but five progressed to chronic constrictive pericardial disease. The chronic constrictive pericarditis occurred in association with chronic pericardial effusion (seven cases) and with myocardial fibrosis and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Keith E. Cohn, M.D.; J. Robert Stewart, M.D.; Luis F. Fajardo, M.D.; E. William Hancock, M.D., F.A.C.P.Affiliations: Palo Alto, California PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1967Volume 66, Issue 5Page: 1035-1036KeywordsCardiovascular therapyMyocardial fibrosisPericardial diseasesProteinsRadiation therapyThorax ePublished: 1 December 2008 Issue Published: 1 May 1967 PDF downloadLoading ...
Exportability of managed care is limited
Authors: David Woods
Journal: BMJ (1997)

Although managed care has swept through the United States, its exportability to Britain and the rest of Europe is limited, concluded speakers at a meeting in Washington, DC, last week.

Managed care is a system of fixed prepayment for comprehensive healthcare coverage in which the companies providing it control costs by curbing use. Speakers attending Exporting Managed Care to Europe were in general agreement that wholesale adoption of a system that covers some 140 million Americans was impossible but that …
Hepatic expression of inducible nitric oxide synthase transcripts in chronic hepatitis C virus infection: Relation to hepatic viral load and liver injury
Authors: S Mihm, A Fayyazi, G Ramadori
Journal: Hepatology (1997)

Hepatitis C virus (HCV) causes acute and often also chronic liver disease. Hepatocellular injury might result from both a host response directed to inhibit viral spread and from processes initiated by the virus itself. To study mechanisms involved in hepatocellular injury, liver tissue from chronically HCV-infected patients was analyzed for the expression of the inducible isoform of nitric oxide synthase (iNOS) and for interferon γ (IFN-γ) by a quantitative, competitive reverse-transcription-polymerase chain reaction (RT-PCR) technique. Moreover, hepatic viral load was determined by two independent techniques, and liver tissue was evaluated histopathologically in detail. Liver tissue from HCV-infected patients was shown to express elevated levels of iNOS transcripts compared with non-HCV-infected patients. Increased iNOS transcript expression, however, was not accompanied by significantly elevated serum nitrite plus nitrate (NOx) concentration, although some of the chronic HCV-infected patients reached markedly higher serum NOx levels than the control group or healthy individuals, respectively. Hepatic iNOS expression was found to be positively correlated to hepatic HCV-RNA content on the one hand, and weakly to hepatic IFN-γ expression, previously shown to be solely associated with hepatic necro-inflammatory activity among the histopathological parameters studied, on the other hand. In contrast to IFN-γ transcript expression, neither hepatic iNOS expression nor hepatic HCV-RNA content were related to hepatic inflammatory activity. The presented data are compatible with the assumption that HCV might be able to stimulate iNOS expression both directly and indirectly via its capacity to induce IFN-γ.
Pharmacodynamics of thrombolysis with recombinant tissue-type plasminogen activator. Correlation with characteristics of and clinical outcomes in patients with acute myocardial infarction. The TAMI Study Group.
Authors: D C Stump, R M Califf, E J Topol, K Sigmon, D Thornton, R Masek, L Anderson, D Collen
Journal: Circulation (1989)

Coagulation analysis was performed on blood samples from 386 patients with acute myocardial infarction drawn before, during, and after a continuous intravenous infusion of 150 mg recombinant tissue-type plasminogen activator (rt-PA) (Activase). Plasma rt-PA rose to peak levels of 2.1 +/- 3.1 micrograms/ml (mean +/- SD). Fibrinogen levels measured by coagulation rate and by sulfite precipitation decreased from baseline levels of 3.0 +/- 0.9 and 3.2 +/- 1.0 g/l, respectively, to nadir levels of 1.4 +/- 0.75 and 1.8 +/- 0.92 g/l, respectively, and were associated with peak levels in serum of fibrinogen-degradation products (FDP) of 230 +/- 470 micrograms/ml. Forty percent of patients experienced a nadir functional-fibrinogen level of less than 1.0 g/l, whereas 20% fell below 0.5 g/l. Nadir fibrinogen levels did not correlate with patency of the infarct-related coronary artery at 90 minutes or with risk of coronary vessel reocclusion within 7-10 days. However, the risk of coronary artery reocclusion was inversely related to the baseline functional fibrinogen level (p = 0.0008), with the magnitude of its drop to nadir level (p = 0.0003) as well as to peak levels of FDP (p = 0.038). Quantitative blood loss correlated with all markers for systemic fibrinogenolysis including nadir fibrinogen level (r = -0.20, p = 0.0011), percent decrease of fibrinogen (r = 0.22, p = 0.001), and peak FDP levels (r = 0.14, p = 0.020). Both patients who experienced intracranial hemorrhage presented with high baseline fibrinogen levels and experienced extensive degradation of coagulable fibrinogen. Overall, patients at greatest risk of systemic fibrinogenolysis tended to be relatively older women with lower body weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinetics of hepatitis C (HCV) viraemia and quasispecies during treatment of HCV associated cryoglobulinaemia with pulse cyclophosphamide
Authors: J Thiel
Journal: Annals of the Rheumatic Diseases (2002)

To investigate the effect of pulse cyclophosphamide treatment on hepatitis C virus (HCV) kinetics and quasispecies in interferon alpha (IFNalpha) resistant HCV related cryoglobulinaemic vasculitis.Reports on two patients with severe manifestations of HCV related cryoglobulinaemia who failed to respond to interferon alpha are given. Both patients were treated with pulse cyclophosphamide (750-1000 mg/month for six and 11 months, respectively). HCV RNA was quantified and HCV quasispecies determined in cryoprecipitates and supernatants before and during treatment.Cryocrit and complement activation decreased in both patients with rebound of cryocrit in one case during continuing pulse cyclophosphamide treatment. Vasculitic symptoms improved. Alanine aminotransferase (ALT) levels and HCV viral load (0.2-0.4 log) increased slightly and reached pretreatment levels after cyclophosphamide was stopped. A highly heterogeneous quasispecies was found in the cryoprecipitate and supernatant of one patient, whereas the viral population was homogeneous in the other patient. After six cycles of cyclophosphamide, viral distances decreased non-significantly. However, phylogenetic analysis showed the evolution of distinct viral strains in one patient and replacement of the main viral population by another population in the second patient.Immunosuppressive treatment with pulse cyclophosphamide has a temporary limited effect on HCV associated cryoglobulinaemia and leads to a reversible increase of ALT levels and HCV viral load. Short term immunosuppression does not affect the viral heterogeneity as measured by amino acid and nucleotide distances in the hypervariable region 1 of HCV. A change of quasispecies was observed, but further studies are needed to evaluate if this does affect the outcome of IFNalpha treatment in such patients.
Preliminary Results of a Differentiated Emotion-Stimulating Interview in Patients with Essential Hypertension as Compared with Inpatients of a Psychosomatic Unit and Normal Controls
Authors: H.-C. Deter, A. Klepper, K.H. Schulte
Journal: Psychotherapy and Psychosomatics (1996)

Background: The question of psychophysiologic reaction specificity is still controversial. Methods: Blood pressure and heart rate were measured for different emotional effects induced during a semistandardized interview. Results: Generally, a stronger increase in blood pressure was observed in hypertensive patients than in inpatients of a psychosomatic unit and normal controls. Differences related to various phases of the stress interview (regarding feelings of aggression, rage and anger, professional situation) were statistically significant as compared to controls, not only in hypertensives but also in the inpatients of a psychosomatic unit. Conclusions: The results are discussed with respect to the specificity theory of Alexander.
Drug Identification Guide
Authors: Walter E. Heck
Journal: JAMA (1963)

<h3>To the Editor:</h3> —The Drug Identification Guide (<i>JAMA</i><b>182</b>:1145 [Dec 22] 1962) is excellent and obviously represents a great deal of thought and work. Would it not be a further step forward if the manufacturers would put the name, or a short abbreviation thereof, on each tablet and capsule? Obviously this could be done, since various insignia are now imprinted. Occasionally, perhaps, a hand lens would be necessary in order to read the name.
Abstract 4486: OSI-027, a selective dual mTORC1/TORC2 kinase inhibitor displays broad spectrum anti-tumor activity in preclinical models of human cancer
Authors: Prafulla C. Gokhale, Shripad V. Bhagwat, Andrew P. Crew, Andrew Cooke, Christine Mantis, Jennifer E. Workman, Darla Landfair, Mark Bittner, David M. Epstein, Jonathan A. Pachter, Robert Wild
Journal: Cancer Research (2010)

Abstract The mammalian target of rapamycin (mTOR) protein kinase plays a central role in regulating cell proliferation and cell survival. The PI3K/AKT signaling pathway that activates mTOR is frequently altered in many human cancers. mTOR exists as multi-protein complexes with distinct signaling functions. Complexes containing mTOR and RAPTOR (mTORC1) phosphorylate S6K and 4E-BP1 and are rapamycin sensitive. Whereas, complexes that contain mTOR and RICTOR (mTORC2) phosphorylate AKT and 4E-BP1 and are insensitive to rapamycin treatment. OSI-027 is a selective small molecule dual inhibitor of both mTORC1 and mTORC2 kinase activity with biochemical IC50 values of 22 nM and 65 nM, respectively. In the MDA-MB 231 breast carcinoma xenograft model, a single 65 mg/kg oral dose of OSI-027 resulted in significant inhibition of 4E-BP1 phosphorylation (&amp;gt;70%) up to 16 h in tumor tissue. At 24 h post-dose, 59% inhibition of phospho-4E-BP1 was observed with a corresponding plasma OSI-027 concentration of 2.2 μM. Consistent with its ability to inhibit mTORC2 in vitro, a single dose of 65 mg/kg also resulted in significant inhibition of phospho-AKT (Ser473) for up to 8 hours with slow recovery thereafter. Such extended target suppression at 65 mg/kg was associated with significant efficacy corresponding to 100% tumor growth inhibition (TGI) with 19% regression in the MDA-MB 231 xenograft model when dosed for 14 consecutive days. In comparison, a lower dose of 25 mg/kg resulted in only 39% TGI which corresponded with a shorter duration of pharmacodynamic effects in vivo. In particular, at the 25 mg/kg dose, inhibition of 4E-BP1 phosphorylation was observed only up to 8 h in tumor tissue with return to predose levels by 16 h which corresponded with plasma drug concentrations of &amp;lt;0.1 µM. These data suggest that maximal anti-tumor efficacy may require plasma levels sufficient to chronically suppress phospho-4E-BP1 in tumor tissue. In addition to significant efficacy in MDA-MB 231 breast carcinoma model, OSI-027 demonstrated robust anti-tumor activity in several different human xenograft models representing different histologies, including colon carcinomas, non-small cell lung carcinomas and ovarian carcinomas. These preclinical studies indicate that OSI-027, a dual mTORC1/2 kinase inhibitor, may show broad spectrum anti-tumor activity, including superior efficacy compared to mTORC1-selective rapalogs against some human cancers. OSI-027 is currently being evaluated in Phase I clinical studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4486.
Athletic injuries. Application of epidemiologic methods
Authors: J. M. Robey
Journal: JAMA (1971)

The application of epidemiologic methods in determining the nature and extent of athletic injuries occurring in high school football shows that (1) no significant difference in the rate of injury for players based on time exposed to risk exists, (2) injury risk increases with age, (3) a student with a history of prior football injury sustains injury at a significantly higher rate than his associates with no history, and (4) certain types of protective equipment are associated with greater injury incidence. These data are part of a five-year continuing study of athletes in 43 high schools.
Pancreatic Abscess With Haemophilus influenzae and Eikenella corrodens
Authors: Larry I. Lutwick
Journal: JAMA (1976)

An infected pancreatic pseudocyst was caused in part by<i>Haemophilus influenzae</i>and<i>Eikenella corrodens</i>. To my knowledge, neither organism has been isolated previously from pancreatic abscesses. I believe that the infecting bacteria originated in the oropharynx and descended through the duodenum. (<i>JAMA</i>236:2091-2092, 1976)
Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity
Authors: Frédéric Chibon, Pauline Lagarde, Sébastien Salas, Gaëlle Pérot, Véronique Brouste, Franck Tirode, Carlo Lucchesi, Aurélien de Reynies, Audrey Kauffmann, Binh Bui, Philippe Terrier, Sylvie Bonvalot, Axel Le Cesne, Dominique Vince-Ranchère, Jean-Yves Blay, Françoise Collin, Louis Guillou, Agnès Leroux, Jean-Michel Coindre, Alain Aurias
Journal: Nature Medicine (2010)
Amelioration of Angiotensin II–Induced Cardiac Injury by a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor
Authors: Ralf Dechend, Anette Fiebeler, Joon-Keun Park, Dominik N. Muller, Juergen Theuer, Eero Mervaala, Markus Bieringer, Dietrich Gulba, Rainer Dietz, Friedrich C. Luft, Hermann Haller
Journal: Circulation (2001)

Background 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have effects that extend beyond cholesterol reduction. We used an angiotensin (Ang) II–dependent model to test the hypothesis that cerivastatin ameliorates cardiac injury. Methods and Results We treated rats transgenic for human renin and angiotensinogen (dTGR) chronically from weeks 4 to 7 with cerivastatin (0.5 mg/kg by gavage). We used immunohistochemistry, electrophoretic mobility shift assays, and reverse transcription–polymerase chain reaction techniques. Compared with control dTGR, dTGR treated with cerivastatin had reduced mortality, blood pressure, cardiac hypertrophy, macrophage infiltration, and collagen I, laminin, and fibronectin deposition. Basic fibroblast growth factor mRNA and protein expression were markedly reduced, as was interleukin-6 expression. The transcription factors NF-κB and AP-1 were substantially less activated, although plasma cholesterol was not decreased. Conclusions These results suggest that statins ameliorate Ang II–induced hypertension, cardiac hypertrophy, fibrosis, and remodeling independently of cholesterol reduction. Although the clinical significance remains uncertain, the results suggest that statins interfere with Ang II–induced signaling and transcription factor activation, thereby ameliorating end-organ damage.
Pancreatic cancer: state-of-the-art care
Authors: K. D. Lillemoe, C. J. Yeo, J. L. Cameron
Journal: CA A Cancer Journal for Clinicians (2000)

This review focuses on the pathogenesis, diagnosis, staging, and treatment of pancreatic cancer. Although much is needed to improve the still dismal outlook for patients with this disease, significant progress has been made in its surgical and oncologic management. Furthermore, our deepening understanding of the molecular genetics of pancreatic cancer lends hope for the possibility of earlier detection, which would result in substantial improvements in survival.
Differences in microbial signatures between rectal mucosal biopsies and rectal swabs
Authors: Félix Araújo-Pérez, Amber N. McCoy, Charles Okechukwu, Ian M. Carroll, Kevin M. Smith, Kim Jeremiah, Robert S. Sandler, Gary N. Asher, Temitope O. Keku
Journal: Gut Microbes (2012)

There is growing evidence the microbiota of the large bowel may influence the risk of developing colorectal cancer as well as other diseases including type-1 diabetes, inflammatory bowel diseases and irritable bowel syndrome. Current sampling methods to obtain microbial specimens, such as feces and mucosal biopsies, are inconvenient and unappealing to patients. Obtaining samples through rectal swabs could prove to be a quicker and relatively easier method, but it is unclear if swabs are an adequate substitute. We compared bacterial diversity and composition from rectal swabs and rectal mucosal biopsies in order to examine the viability of rectal swabs as an alternative to biopsies. Paired rectal swabs and mucosal biopsy samples were collected in un-prepped participants (n = 11) and microbial diversity was characterized by Terminal Restriction Fragment Length polymorphism (T-RFLP) analysis and quantitative polymerase chain reaction (qPCR) of the 16S rRNA gene. Microbial community composition from swab samples was different from rectal mucosal biopsies (p = 0.001). Overall the bacterial diversity was higher in swab samples than in biopsies as assessed by diversity indexes such as: richness (p = 0.01), evenness (p = 0.06) and Shannon's diversity (p = 0.04). Analysis of specific bacterial groups by qPCR showed higher copy number of Lactobacillus (p < 0.0001) and Eubacteria (p = 0.0003) in swab samples compared with biopsies. Our findings suggest that rectal swabs and rectal mucosal samples provide different views of the microbiota in the large intestine.
Heritability of Risk for Sudden Cardiac Arrest in ESRD
Authors: Kevin E. Chan, Christopher Newton-Cheh, James F. Gusella, Franklin W. Maddux
Journal: Journal of the American Society of Nephrology (2015)

Patients on dialysis are 20 times more likely to have a cardiac arrest compared with the general population. We considered whether inherited factors associate with cardiac arrest among patients on dialysis. From a sample of 647,457 patients on chronic dialysis, we identified 5117 pairs of patients who came from the same family. These patients were each matched to a control subject from the same population. McNemar’s tests were used to compare the risk of cardiac arrest between the familial related and unrelated pairs. Genetically related family members who did not cohabitate had an odds ratio of 1.88 (95% confidence interval [95% CI], 1.25 to 2.84) for cardiac arrest compared with their phenotypically matched unrelated controls. Genetically related family members who lived together in the same environment had an odds ratio of 1.66 (95% CI, 1.20 to 2.28). Spouses, who are genetically unrelated but live together in the same environment, had an odds ratio of 0.95 (95% CI, 0.60 to 1.59) for cardiac arrest. The risk of cardiac arrest in patients on dialysis may be attributable to inherited factors. Additional studies are needed to identify such candidate genes that modify cardiovascular risk in ESRD.
Chlamydia was most often reported infection in Europe in 2006, new data show
Authors: R. Watson
Journal: BMJ (2008)

Artificial intelligence (AI) is an exciting field combining computer science with robust data sets to facilitate problem-solving. It has the potential to transform education, practice and delivery of healthcare especially in orthopaedics. This review article outlines some of the already used AI pathways as well as recent technological advances in orthopaedics. Additionally, this article further explains how potentially these two entities could be combined in the future to improve surgical education, training and ultimately patient care and outcomes.
Cysteamine or N-acetylcysteine for paracetamol poisoning?
Authors: L F Prescott, M J Stewart, A T Proudfoot
Journal: BMJ (1978)

SIR,-We agree about the term mercaptamine.It was imposed upon us by editorial policy in place of the more commonly used cysteamine.We have now adopted the method of Glynn and Kendal,' which measures "free" paracetamol.This method had not been described at the beginning of our study.The other methods
Prognostic Role and HER2 Expression of Circulating Tumor Cells in Peripheral Blood of Patients Prior to Radical Cystectomy: A Prospective Study
Authors: Michael Rink, Felix K. Chun, Roland Dahlem, Armin Soave, Sarah Minner, Jens Hansen, Malgorzata Stoupiec, Cornelia Coith, Luis A. Kluth, Sascha A. Ahyai, Martin G. Friedrich, Shahrokh F. Shariat, Margit Fisch, Klaus Pantel, Sabine Riethdorf
Journal: European Urology (2012)