tbuckley/cabot-search huggingface dataset:
Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development.
Authors: R Khanna, S R Burrows, M G Kurilla, C A Jacob, I S Misko, T B Sculley, E Kieff, D J Moss
Journal: The Journal of Experimental Medicine (1992)

There is considerable interest in designing an effective vaccine to the ubiquitous Epstein-Barr virus (EBV). An important role for EBV-specific cytotoxic T lymphocytes (CTLs) in eliminating virus-infected cells is well established. Limited studies using a small number of immune donors have defined target epitopes within the latent antigens of EBV. The present study provides an extensive analysis of the distribution of class I-restricted CTL epitopes within EBV-encoded proteins. Using recombinant vaccinia encoding individual EBV latent antigens (Epstein-Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, LP, and LMP 1), we have successfully localized target epitopes recognized by CTL clones from a panel of 14 EBV-immune donors. Of the 20 CTL epitopes localized, five were defined at the peptide level. Although CTL clones specific for nine epitopes recognized both type 1 and type 2 transformants, a significant number of epitopes (7/16 epitopes for which EBV type specificity was determined) were detected only on type 1 EBV transformants. Vaccinia recombinants encoding EBNA 3A and EBNA 3C were recognized more frequently than any other vaccinia recombinants used in this study, while no CTL epitopes were localized in EBNA 1. Surprisingly, epitope specificity for a large number of EBV-specific CTL clones could not be localized, although vaccinia recombinants used in this study encoded most of the latent antigens of EBV. These results suggest that any EBV vaccine based on CTL epitopes designed to provide widespread protection will need to include not only latent antigen sequences but also other regions of the genome. The apparent inability of human CTLs to recognize EBNA 1 as a target antigen, often the only latent antigen expressed in Burkitt's lymphoma and nasopharyngeal carcinoma, suggests that EBV-specific CTL control of these tumors will not be feasible unless the down-regulation of latent antigens can be reversed.
Global gene expression profiling of cells overexpressing SMC3.
Authors: Giancarlo Ghiselli, Chang-Gong Liu
Journal: Molecular Cancer (2005)

The Structural Maintenance of Chromosome 3 protein (SMC3) plays an essential role during the sister chromatid separation, is involved in DNA repair and recombination and participates in microtubule-mediated intracellular transport. SMC3 is frequently elevated in human colon carcinoma and overexpression of the protein transforms murine NIH3T3 fibroblasts. In order to gain insight into the mechanism of SMC3-mediated tumorigenesis a gene expression profiling was performed on human 293 cells line stably overexpressing SMC3. Biotinylated complementary RNA (cRNA) was used for hybridization of a cDNAmicroarray chip harboring 18,861 65-mer oligos derived from the published dEST sequences. After filtering, the hybridization data were normalized and statistically analyzed. Sixty-five genes for which a putative function could be assigned displayed at least two-fold change in their expression level. Eighteen of the affected genes is either a transcriptional factor or is involved in DNA and chromatin related mechanisms whereas most of those involved in signal transduction are members or modulators of the ras-rho/GTPase and cAMP signaling pathways. In particular the expression of RhoB and CRE-BPa, two mediators of cellular transformation, was significantly enhanced. This association was confirmed by analyzing the RhoB and CRE-BPa transcript levels in cells transiently transfected with an SMC3 expression vector. Consistent with the idea that the activation of ras-rho/GTPase and cAMP pathways is relevant in the context of the cellular changes following SMC3 overexpression, gene transactivation through the related serum (SRE) and cAMP (CRE) cis-acting response elements was significantly increased. We have documented a selective effect of the ectopic expression of SMC3 on a set of genes and transcriptional signaling pathways that are relevant for tumorigenesis. The results lead to postulate that RhoB and CRE-BPa two known oncogenic mediators whose expression is significantly increased following SMC3 overexpression play a significant role in mediating SMC3 tumorigenesis.
Poly(ADP-Ribose) Polymerase Is Activated in Subjects at Risk of Developing Type 2 Diabetes and Is Associated With Impaired Vascular Reactivity
Authors: Csaba Szabó, Anne Zanchi, Katalin Komjáti, Pál Pacher, Andrzej S. Krolewski, William C. Quist, Frank W. LoGerfo, Edward S. Horton, Aristidis Veves
Journal: Circulation (2002)

Background— We have previously shown that endothelial function is impaired not only in diabetes but also in subjects at risk of developing type 2 diabetes. We hypothesized that changes in the expression or activity of the endothelial isoform of nitric oxide synthase (eNOS), the receptor for advanced glycation end products (RAGE), and poly(ADP-ribose) polymerase (PARP) are related to this impairment. Methods and Results— We included a control group of 21 healthy subjects, a group of 22 healthy individuals with parental history of type 2 diabetes, a group of 23 subjects with impaired glucose tolerance, and a group of 21 type 2 diabetic patients. Two 2-mm forearm skin biopsies were taken from each participant and used for measurements. The percentage of PARP-positive endothelial nuclei was higher in the group with parental history of type 2 diabetes and diabetic patients compared with the controls ( P &lt;0.001). Immunoreactivity for nitrotyrosine (a marker of reactive nitrogen species) was higher in the diabetic group compared with all other groups ( P &lt;0.01). No differences in the expression of eNOS and RAGE were found among all 4 groups. The polymorphism of the eNOS gene was also studied and was not found to influence eNOS expression or microvascular functional measurements. Conclusions— PARP activation is present in healthy subjects at risk of developing diabetes as well as in established type 2 diabetic patients, and it is associated with impairments in the vascular reactivity in the skin microcirculation.
Uncertainty Over DAT Testing
Authors: C. Schmidt
Journal: JNCI Journal of the National Cancer Institute (2012)

Dr. Kimberly Lovett was frustrated. Her patient had tested positive on the fecal occult blood test used in colon cancer screening, and as a primarycare doctor in the Department of Family and Preventive Medicine at the University of California, San Diego, Lovett knew the next step in confirming the diagnosis was a colonoscopy. “But why can’t you order the blood test?” demanded her patient, determined to avoid colonoscopy at all costs. Lovett responded that such a test doesn’t exist, yet the patient was adamant that it did—he claimed to have seen it advertised by a Web-based company that sells blood biomarker analyses. After a tense conversation, Lovett’s patient was convinced that the ad had misled him, but he left bewildered, wondering why a company can claim it can diagnose colon cancer when it can’t. Many practicing physicians wonder the
Lipoprotein (a) concentrations, apolipoprotein (a) phenotypes, and peripheral arterial disease in three independent cohorts
Authors: A. Laschkolnig, B. Kollerits, C. Lamina, C. Meisinger, B. Rantner, M. Stadler, A. Peters, W. Koenig, A. Stockl, D. Dahnhardt, C. A. Boger, B. K. Kramer, G. Fraedrich, K. Strauch, F. Kronenberg
Journal: Cardiovascular Research (2014)

The relevance of lipoprotein(a) [Lp(a)] concentrations and low-molecular-weight (LMW) apo(a) phenotypes in peripheral arterial disease (PAD) has only been investigated by few studies. Therefore, we analysed this association in three independent cohorts and performed a Mendelian Randomization approach using instrumental variable regression.Lp(a) concentrations, apo(a) phenotypes, and one SNP in the LPA gene (rs10455872) were measured in the CAVASIC study, including 241 male patients with intermittent claudication and 246 age- and diabetes-matched controls as well as in the two population-based studies KORA F3 (n = 3184) and KORA F4 (n = 3080). In KORA F3/F4, 109/80 persons suffered from intermittent claudication, 200/144 from PAD, and 128/103 showed an ankle-brachial index (ABI) <0.9. In CAVASIC, adjusted logistic regression analyses revealed significant associations between an increase of log-Lp(a) per one standard deviation (SD) (OR = 1.28, P = 0.02) as well as LMW apo(a) phenotypes and symptomatic PAD (OR = 1.65, P = 0.03). Linear regression models with continuous ABI showed a significant association in the combined analyses of KORA F3/F4: an increase in log-Lp(a) per one SD (β = -0.006, P = 0.005) and the presence of LMW apo(a) phenotypes (β = -0.011, P = 0.02) or the minor allele of rs10455872 (ß = -0.016, P = 0.03) were associated with a decrease in ABI in the fully adjusted linear and instrumental variable regression models.Analyses in three independent populations showed significant associations of Lp(a) concentrations, LMW apo(a) phenotypes, and rs10455872 with PAD. This points to a causal relationship between Lp(a) and PAD since the genetically determined apo(a) phenotypes and SNP alleles are indeed associated with PAD.
Effects of Vitamin A on 3-Methylcholanthrene-Induced Squamous Metaplasias and Early Tumors in the Respiratory Tract of Rats 2
Authors: M. Virginia Cone, P. Nettesheim
Journal: JNCI Journal of the National Cancer Institute (1973)

The influence of high levels of vitamin A on the susceptibility of respiratory-tract epithelium to the metaplastogenic and tumorigenic effects of 3-methylcholanthrene (MCA) was tested in rats. Fischer-344 rats were maintained on a vitamin A-free diet and were given either 1740 µg or 2×87 µg retinyl acetate twice a week intragastrically. At 9 weeks of age each rat received 2 intratracheal injections of 5 mg MCA. Groups of 4–5 rats were killed 2, 3, 5, 8, and 12 weeks after carcinogen administration. Vitamin A storage in the liver, assessed at 3 different times, corresponded to the vitamin A dose. The number of microscopic hyperplastic and metaplastic lesions and grossly visible tumor nodules per rat lung was determined. The development of squamous metaplasias and squamous cell tumors was significantly reduced in rats receiving a high dose of retinyl acetate. Our experiments confirm earlier findings suggesting an inhibitory effect of vitamin A on the development of respiratory-tract tumors in hamsters.
Maximal shuttle running over 40 m as a measure of anaerobic performance.
Authors: J Baker, R Ramsbottom, R Hazeldine
Journal: British Journal of Sports Medicine (1993)

Over the last decade increasing interest has been shown in the measurement of anaerobic power and capacity in athletic men. These physiological characteristics have been determined predominantly using cycle ergometry and treadmill sprinting. The purpose of the present study was to examine the relationship between 40-m maximal shuttle run times and performance indices obtained during treadmill sprinting and cycle ergometry. Moderate correlations were found between 10-m split times (the time taken to cover the initial 10 m of the shuttle course) and treadmill peak power outputs (r = -0.67; P < 0.05). Similar relationships were also found between the fastest 40-m time and mean power outputs generated on both the treadmill and cycle ergometer (r = -0.67; P < 0.05) and (r = -0.75; P < 0.05) respectively. The correlations remained unchanged when the values were adjusted for body weight (W kg-1). The results of the present study suggest that maximal 40-m shuttle running ability may reflect anaerobic indices of power and capacity, determined using standard laboratory procedures.
In Vitro Lysis of Tumor Cells by Antibody and Complement: Detection of Antibody With Low Cytotoxic Reactivity 2
Authors: S. O. DiSciullo, D. C. Laux
Journal: JNCI Journal of the National Cancer Institute (1977)

The factors affecting the in vitro lysis of PARA-7 tumor cells mediated by antibody and complement were examined with the use of the 51Cr-release assay. The addition of immune syngeneic hamster antisera (HA) to 51Cr-labeled PARA-7 target cells 30 minutes before the addition of guinea pig complement (GPC) failed to produce significant levels of lysis. Similarly, the addition of rabbit anti-PARA-7 serum (RAS) 30 minutes prior to the addition of GPC resulted in low levels of lysis. Longer incubations in the presence of RAS, but not RAS and GPC, increased levels of lysis. Extended incubation in the presence of RAS increased the amount of antibody bound to the target cells. This increase did not appear to be due to the expression of additional antigen, because the increase occurred at 4 degrees C and was not sensitive to inhibitors of protein synthesis. The inability to obtain increased levels of lysis by extended incubation in the presence of both RAS and GPC appeared to be due to the inhibitory effects of GPC on the interaction of antibody and antigen. Similar inhibitory effects could be produced by inactivated GPC and various other substances. When extended incubations in the presence of antiserum were used for the reexamination of the cytolytic activity of syngeneic immune HA, significant lysis was detectable.
The protective effect of delta-aminolevulinic acid dehydratase 1-2 and 2-2 isozymes against blood lead with higher hematologic parameters.
Authors: Hee-Seon Kim, Sung-Soo Lee, Gap-Soo Lee, Young Hwangbo, Kyu-Dong Ahn, Byung-Kook Lee
Journal: Environmental Health Perspectives (2003)

Previous studies have suggested that delta-aminolevulinic acid dehydratase (ALAD) types 1-2 or 2-2 are protective against the toxicity of blood lead (PbB) when zinc protoporphyrin (ZPP) levels are low because of differential binding of lead in erythrocytes. The hypothesis is that subjects with the ALAD 1-1 genotype are more susceptible to lead exposure with impaired hematologic synthesis and therefore that iron nutrition is more important in those with the ALAD 1-1 genotype. The purpose of this study was to prove the protective effect of ALAD 1-2/2-2 against PbB with higher hematologic parameters. Data on 1,219 male workers from eight lead-using factories in the Republic of Korea were examined in this cross-sectional study. Blood samples were evaluated for PbB, ZPP, hemoglobin (Hb), and serum iron (SFe) concentrations and ALAD genotypes. The overall prevalence of the ALAD 1-2/2-2 genotype was 9.3%, which was associated with lower log ZPP (p < 0.001) and higher Hb (p = 0.014) levels. For the subjects with normal iron status (SFe levels > 60 micro g/dL), those with the ALAD 1-1 genotype were more likely to be anemic (adjusted odds ratio of 5.2; 95% confidence interval, 1.2-22.6) than those with ALAD 1-2/2-2. The study confirms the protective effects of ALAD 1-2/2-2 polymorphisms against PbB on hematologic pathways. In order to promote health and to minimize the toxicity of lead exposure more effectively, the nutritional management of iron in Korean workers should take both their ALAD genotypes and occupational lead exposures into account.
Relation of Disease Pathogenesis and Risk Factors to Heart Failure With Preserved or Reduced Ejection Fraction
Authors: Douglas S. Lee, Philimon Gona, Ramachandran S. Vasan, Martin G. Larson, Emelia J. Benjamin, Thomas J. Wang, Jack V. Tu, Daniel Levy
Journal: Circulation (2009)

The contributions of risk factors and disease pathogenesis to heart failure with preserved ejection fraction (HFPEF) versus heart failure with reduced ejection fraction (HFREF) have not been fully explored.We examined clinical characteristics and risk factors at time of heart failure onset and long-term survival in Framingham Heart Study participants according to left ventricular ejection fraction < or =45% (n=314; 59%) versus >45% (n=220; 41%) and hierarchical causal classification. Heart failure was attributed to coronary heart disease in 278 participants (52%), valvular heart disease in 42 (8%), hypertension in 140 (26%), or other/unknown causes in 74 (14%). Multivariable predictors of HFPEF (versus HFREF) included elevated systolic blood pressure (odds ratio [OR]=1.13 per 10 mm Hg; 95% confidence interval [CI], 1.04 to 1.22), atrial fibrillation (OR=4.23; 95% CI, 2.38 to 7.52), and female sex (OR=2.29; 95% CI, 1.35 to 3.90). Conversely, prior myocardial infarction (OR=0.32; 95% CI, 0.19 to 0.53) and left bundle-branch block QRS morphology (OR=0.21; 95% CI, 0.10 to 0.46) reduced the odds of HFPEF. Long-term prognosis was grim, with a median survival of 2.1 years (5-year mortality rate, 74%), and was equally poor in men and women with HFREF or HFPEF.Among community patients with new-onset heart failure, there are differences in causes and time-of-onset clinical characteristics between those with HFPEF versus HFREF. In people with HFREF, mortality is increased when coronary heart disease is the underlying cause. These findings suggest that heart failure with reduced left ventricular systolic function and heart failure with preserved left ventricular systolic function are partially distinct entities, with potentially different approaches to early detection and prevention.
Deoxyspergualin in relapsing and refractory Wegener's granulomatosis
Authors: O Flossmann, B Baslund, A Bruchfeld, J W Cohen Tervaert, C Hall, P Heinzel, B Hellmich, R A Luqmani, K Nemoto, V Tesar, D R W Jayne
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> Conventional therapy of Wegener's granulomatosis with cyclophosphamide and corticosteroids is limited by incomplete remissions and a high relapse rate. The efficacy and safety of an alternative immunosuppressive drug, deoxyspergualin, was evaluated in patients with relapsing or refractory disease. <h3>Methods:</h3> A prospective, international, multicentre, single-limb, open-label study. Entry required active Wegener's granulomatosis with a Birmingham vasculitis activity score (BVAS) ⩾4 and previous therapy with cyclophosphamide or methotrexate. Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status. Deoxyspergualin, 0.5 mg/kg per day, was self-administered by subcutaneous injection in six cycles of 21 days with a 7-day washout between cycles. Cycles were stopped early for white blood count less than 4000 cells/mm<sup>3</sup>. The primary endpoint was complete remission (BVAS 0 for at least 2 months) or partial remission (BVAS &lt;50% of entry score). After the sixth cycle azathioprine was commenced and follow-up continued for 6 months. <h3>Results:</h3> 42/44 patients (95%) achieved at least partial remission and 20/44 (45%) achieved complete remission. BVAS fell from 12 (4–25), median (range) at baseline to 2 (0–14) at the end of the study (p&lt;0.001). Prednisolone doses were reduced from 20 to 8 mg/day (p&lt;0.001). Relapses occurred in 18 (43%) patients after a median of 170 (44–316) days after achieving remission. Severe or life-threatening (⩾ grade 3) treatment-related adverse events occurred in 24 (53%) patients mostly due to leucopaenias. <h3>Conclusions:</h3> Deoxyspergualin achieved a high rate of disease remission and permitted prednisolone reduction in refractory or relapsing Wegener's granulomatosis. Adverse events were common but rarely led to treatment discontinuation.
Reply to Kocsis Letter
Authors: Gordon Parker, Max Fink, Edward Shorter, Michael Alan Taylor, Hagop Akiskal, German Berrios, Tom Bolwig, Walter A. Brown, Bernard Carroll, David Healy, Donald F. Klein, Athanasios Koukopoulos, Robert Michels, Joel Paris, Robert T. Rubin, Robert Spitzer, Conrad Swartz
Journal: American Journal of Psychiatry (2010)
The rhythm of the eyes: Overt and covert attentional pointing
Authors: John M. Findlay, Valerie Brown, Iain D. Gilchrist
Journal: Behavioral and Brain Sciences (1997)

This commentary centres around the system of human visual attention. Although generally supportive of the position advocated in the target article, we suggest that the detailed account overestimates the capacities of active human vision. Limitations of peripheral search and saccadic accuracy are discussed in relation to the division of labour between covert and overt attentional processes.
Efficacy of interferon dose and prediction of response in chronic hepatitis C: Benelux study in 336 patients
Authors: Johannes T. Brouwer, Frederik Nevens, Bernhard Kleter, Andre Elewaut, Michael Alder, Reginald Brenard, Rob A.F.M. Chamuleau, Peter P. Michielsen, Jean Pirotte, Marc L. Hautekeete, Joseph Weber, Nadine Bourgeois, Bettina E. Hansen, Carolien M. Bronkhorst, Fibo J.W. ten Kate, Rudolf A. Heijtink, Johan Fevery, Solko W. Schalm
Journal: Journal of Hepatology (1998)
ABSCESS IN THE BROAD LIGAMENT OF THE UTERUS; RECOVERY: WITH REMARKS ON THIS DISEASE, ON TYPHLITIS, AND ON ABDOMINAL HERNIA BETWEEN THE RECTI MUSCLES
Authors: J. S. Fletcher
Journal: BMJ (1854)

wo 69 .1-1-11ffAl ~MJICATh'IIIIli.W .-boupuOf ~mtfruial Earepe~,I hal bee able to -dy plmcOics1Iy the diferent met Aware that a die tuiuhed French surgieo had opposed the stched appa- n i w rhis tings, I asked him, " Have you ever tried i?rHe candidly and terely replied in the negative, dding, "I am .at4d it ca anawer."This is not a question to be settled by display of erudition or speculative predication.Its eentially practical nature only allows of appeal to experience for its solution.
William Cullen and a missing mind-body link in the early history of placebos
Authors: CE Kerr, I Milne, TJ Kaptchuk
Journal: Journal of the Royal Society of Medicine (2008)

Until the late 18th century, the term ‘placebo’ was used in a religious rather than a medical context: an early Latin translation of the Hebrew Bible, Psalm 116, verse 9, was rendered as Placebo Domine - ‘I will please the Lord’. In the medieval Catholic Church, ‘placebo’ was the term used to refer to a funereal rite - Vespers for the Dead - which employed Psalm 116.1 By the 13th century, the term had taken on a disparaging, secular meaning: mourners paid to attend a funeral to ‘flatter’ the dead, were said to ‘sing placebos’ of false and easy praise. Indeed, in the 14th century, in the Canterbury Tales, Chaucer named his obsequious, flattering courtier Placebo.2

How did the word ‘placebo’ come to mean a medical treatment intended to please a patient? The term appears to have entered common usage sometime in the late 18th century. The 1775 edition of George Motherby's New Medical Dictionary contains no listing on the subject, while the 1785 edition defines ‘placebo’ as ‘a commonplace method or medicine’.3 Arthur Shapiro, a distinguished historian of the placebo, has expressed puzzlement over the changing meaning of ‘placebo’, suggesting ‘the reasons for the introduction of the word placebo into medicine in 1785 are largely unknown’.1

The transition from religious to medical meanings of the word ‘placebo’ can be enlightened by an analysis of the writings of William Cullen (1710-1790), dubbed by one historian ‘the leading British physician of the 18th century’.4 Cullen was the most prestigious and thus influential medical educator of his day, holding chairs in chemistry, theory of medicine and practice of medicine at the University of Edinburgh. Over his lifetime, his famous lectures were attended by thousands of pupils from throughout the Anglo-American world, including many of the early leading figures in American medicine. Thousands of patients consulted Cullen by post and in person at the Edinburgh clinic, including such luminaries as his friend Adam Smith, the famous economist.5

In his historical account of Scottish medicine, Risse6 noted that Cullen ‘employed regular drugs as placebos, although at lower doses’. We have examined the manuscripts of Cullen's clinical lectures,7 which are held in the Historical Library of the Royal College of Physicians of Edinburgh. They offer a valuable insight on how notions of placebo pertaining to religious ritual and flattery became a term referring to a method for pleasing difficult or incurable patients. The Cullen lectures also reveal the medical and social context of placebo use in actual medical practice in the late 18th Century.