tbuckley/cabot-search huggingface dataset:
Adjuvant Combination and Antigen Targeting as a Strategy to Induce Polyfunctional and High-Avidity T-Cell Responses against Poorly Immunogenic Tumors
Authors: Fernando Aranda, Diana Llopiz, Nancy Díaz-Valdés, José Ignacio Riezu-Boj, Jaione Bezunartea, Marta Ruiz, Marta Martínez, Maika Durantez, Cristina Mansilla, Jesús Prieto, Juan José Lasarte, Francisco Borrás-Cuesta, Pablo Sarobe
Journal: Cancer Research (2011)

Low antigen expression and an absence of coimmunostimulatory signals may be partly responsible for the low immunogenicity of many tumors. It may be possible to overcome this situation by defining a combination of adjuvants and antigens that can activate a high-avidity antitumor response. Using the poorly immunogenic B16-OVA melanoma cells as tumor model, we tested different combinations of adjuvants and antigens to treat established tumors. In the absence of exogenous antigens, repeated administration of the TLR7 ligand Imiquimod together with anti-CD40 agonistic antibodies activated only innate immunity, which was insufficient to reject intradermal tumors. Administering this adjuvant combination together with OVA as a tumor antigen induced T-cell responses that delayed tumor growth. However, administering a combination of anti-CD40 plus TLR3 and TLR7 ligands, together with antigen targeting to dendritic cells through TLR4, was sufficient to induce tumor rejection in 50% of mice. This response was associated with a greater activation of innate immunity and induction of high-avidity polyfunctional CD8(+) T-cell responses, which each contributed to tumor rejection. This therapy activated T-cell responses not only against OVA, which conferred protection against a rechallenge with B16-OVA cells, but also activated T-cell responses against other melanoma-associated antigens. Our findings support the concept that multiple adjuvant combination and antigen targeting may be a useful immunotherapeutic strategy against poorly immunogenic tumors.
Myocarditis in patients with clinical presentation of myocardial infarction and normal coronary angiograms
Authors: Laure Sarda, Patrice Colin, Franck Boccara, Doumit Daou, Rachida Lebtahi, Marc Faraggi, Charles Nguyen, Ariel Cohen, Michel S Slama, Philippe G Steg, Dominique Le Guludec
Journal: Journal of the American College of Cardiology (2001)
Cardiac Aspects of Friedreich's Ataxia
Authors: SAMUEL H. BOYER, ARTHUR W. CHISHOLM, VICTOR A. MCKUSICK
Journal: Circulation (1962)

Twenty-seven kindreds with Friedreich's ataxia were seen at the Johns Hopkins Hospital from 1935 to 1957. In three kindreds the disease exhibited an apparently dominant mode of inheritance. Affected individuals in each of the remaining 24 kindreds were confined to single sibships and in 18 of these limited to a single patient. Thirty-three patients from these kindreds were studied in considerable detail. Follow-up information was obtained on all individuals and electrocardiograms together with chest x-rays were obtained on most of them. Eighteen or 55 per cent exhibited major cardiac abnormalities including cardiac enlargement in four and possible enlargement in an additional two, prominent systolic murmurs in six, a diastolic murmur and other signs suggesting mitral stenosis in one, probable pericardial effusion in another, and major electrocardiographic abnormalities in 16. Two developed atrial fibrillation and one atrial flutter. Heart disease contributed to death definitely in four and possibly in two others of eight patients who have died. Autopsy was performed in two patients; diffuse myocardial fibrosis was found in one of these. An unusual feature of the cardiac disturbance in five patients was the tendency of remission toward normalcy. This finding, together with the supposition that some patients were seen before developing evidence of heart disease, indicates that the frequency of cardiac abnormality probably exceeds the minimum estimate of 55 per cent. In eight patients Friedreich's ataxia with cardiac involvement was mistaken for rheumatic or congenital heart disease. The appearance of leg pains early in the disease increased the mimicry of rheumatic fever in a number of patients. Both cardiac and neurologic manifestations of Friedreich's ataxia are regarded as having a common genetic origin and serve as another example of pleiotropy.
Oxidative stress produced by suprahepatic occlusion and reperfusion
Authors: Beatriz Gonzalez-Flecha, Claudia Reides, Juan C. Cutrin, Susana F. Llesuy, Alberto Boveris
Journal: Hepatology (1993)

In this article the spontaneous chemiluminescence and the steady-state concentration of hydrogen peroxide were determined in rat liver as indicators of oxidative stress in the tissue. Hydroperoxide-initiated chemiluminescence and the activity of antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) were also measured to evaluate antioxidant defenses and serum activity of lactate dehydrogenase and aspartate aminotransferase. Mitochondrial morphology and mitochondrial respiratory control ratio were measured as indicators of cell and mitochondrial damage. Xanthine dehydrogenase and xanthine oxidase activities were determined as a possible source of oxyradicals. No significant changes were observed after 10 or 30 min of vena cava occlusion in any of the measured parameters. In contrast, 10 min of occlusion followed by 10 min of reperfusion increased chemiluminescence (from 18 ± 3 to 32 ± 5 cps/cm 2 ), hydrogen peroxide (from 0.10 ± 0.01 to 0.17 ± 0.01 μmol/L), lactate dehydrogenase (from 80 ± 2 to 330 ± 30 U/L), and aspartate aminotransferase (from 42 ± 2 to 100 ± 10 U/L). Liver reperfusion was also associated with mitochondrial swelling and decreased mitochondrial respiratory control (from 5.6 ± 0.3 to 2.6 ± 0.1). The activity of the antioxidant enzymes and xanthine oxidase was instead without change. After 30 min of vena cava occlusion and 10 min of reperfusion a more marked increase in chemiluminescence (37 ± 5 cps/cm 2 ), hydrogen peroxide (0.30 ± 0.01 μmol/L), lactate dehydrogenase (730 ± 10 U/L) and aspartate aminotransferase (140 ± 10 U/L) was observed. No further changes were found in either mitochondrial morphology or respiratory control (2.4 ± 0.1) in isolated mitochondria. A parallel decrease in the activity of cytosolic (36%) and mitochondrial (57%) superoxide dismutase, catalase (34%) and glutathione peroxidase (34%) was also observed without any change in xanthine oxidase activity. Chain-breaker antioxidants were also diminished as indicated by an increase in the hydroperoxide-initiated chemiluminescence (40%). The results indicate the occurrence of an oxidative stress in association with a sequence of 10 or 30 min of occlusion followed by 10 min of reperfusion. The unchanged activity of xanthine oxidase, the modifications in mitochondrial morphology, the decrease in mitochondrial respiratory control and the relatively high inactivation of the mitochondrial superoxide dismutase indicate that the mitochondria are the main source of oxyradicals during reperfusion. An increased rate of superoxide radical and hydrogen peroxide generation by mitochondria, associated with a decreased activity of antioxidant enzymes, would be the major causes of oxidative stress and the related cell damage. (HEPATOLOGY 1993;18:881-889).
Commentary: problems in Finnish or British data or a true difference?
Authors: S. V P Koskinen
Journal: BMJ (1998)

countries.We need results from Finnish datasets that cover persons with diabetes treated by diet and include information on the disease (type, treatment, duration) and risk factors.British analyses of (pooled?) population based datasets with a large number of deaths would help in assessing the validity of the findings of Chaturvedi et al.The situation in other countries should also be studied.
Plasmapheresis and fulminant acute pancreatitis
Authors: D. Heath, C W Imrie, J A Garrett, M. G Shearer, R B. Hogg, R. L Hughes
Journal: BMJ (1988)

Mean (SD) concentrations oflipids and lipoproteins in patients before and after treatment with corn oil orfish oil Patients treated with corn oil Patients treated with fish oil (n= 17) (n= 16) Before After Before AfterTotal cholesterol 6-4 (1-2) 6-2 (1-4) 6-8 (0-6) 7-0 (0 9) HDL 1-43 (047) 1-47(0-41) 1-28 (037) 1-50 (043)* HDL2 0 57 (0-36) 0-69 (0 30) 0 47 (0 23) 070 (035)** HDL3 0-85 (0 20) 0-79(0-17) 0-81(0-18) 0-79(0-14) LDL 3-99 (1-37) 3-88 (1-03) 4-3 (0-6) 4-5 (0-8) VLDL 1-02 (1-13) 0-87(095) 1 17(067) 095 (064) Triglycerides 1-5 (0-6) 1-4 (0-6) 2-2 (0 9) 1 5 (04)** *p<0-02, **p<O001.Student's t test for paired data.HDL=High density lipoprotein.LDL=Low density lipoprotein.VLDL=Very low density lipoprotein.
Cancer in children of nuclear industry employees: report on children aged under 25 years from nuclear industry family study
Authors: E. Roman, P. Doyle, N. Maconochie, G. Davies, P. G Smith, V. Beral
Journal: BMJ (1999)

To determine whether children of men and women occupationally exposed to ionising radiation are at increased risk of developing leukaemia or other cancers before their 25th birthday.Cohort study of children of nuclear industry employees.Nuclear establishments operated by the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels.39 557 children of male employees and 8883 children of female employees.Cancer incidence in offspring reported by parents. Employment and radiation monitoring data (including annual external dose) supplied by the nuclear authorities.111 cancers were reported, of which 28 were leukaemia. The estimated standardised incidence ratios for children of male and female employees who were born in 1965 or later were 98 (95% confidence interval 73 to 129) and 96 (50 to 168) for all malignancies and 109 (61 to 180) and 95 (20 to 277) for leukaemia. The leukaemia rate in children whose fathers had accumulated a preconceptual dose of >/=100 mSv was 5.8 times that in children conceived before their fathers' employment in the nuclear industry (95% confidence interval 1.3 to 24.8) but this was based on only three exposed cases. Two of these cases were included in the west Cumbrian ("Gardner") case-control study. No significant trends were found between increasing dose and leukaemia.Cancer in young people is rare, and our results are based on small numbers of events. Overall, the findings suggest that the incidence of cancer and leukaemia among children of nuclear industry employees is similar to that in the general population. The possibility that exposure of fathers to relatively high doses of ionising radiation before their child's conception might be related to an increased risk of leukaemia in their offspring could not be disproved, but this result was based on only three cases, two of which have been previously reported. High conceptual doses are rare, and even if the occupational association were causal, the number of leukaemias involved would be small; in this study of over 46 000 children, fewer than three leukaemias could potentially be attributed to such an exposure.
Abstract 5538: Development of RNA quality control methods to improve BCR-ABL measurement in whole blood samples
Authors: Lauren M. Stanoszek, Erin L. Crawford, Thomas Blomquist, Paige Willey, James C. Willey
Journal: Cancer Research (2012)

Abstract Measurement of BCR-ABL fusion transcripts in whole blood by quantitative, reverse-transcriptase PCR is a clinically validated method to monitor treatment response in patients with chronic myelogenous leukemia. For example, achieving a three-log or greater reduction in BCR-ABL expression from baseline is considered a Maximum Molecular Response (MMR). A 0.5-log increase from MMR signifies treatment failure sufficient to motivate change in treatment. The purpose of this study was to develop a BCR-ABL test with improved analytical performance characteristics including adequate quality control for RNA degradation or reverse transcription interference and reliable comparison of results across testing sites. To test whether RNA degradation could mask a 0.5-log increase in expression, an RNA degradation model was established by incubating whole blood from each of six individuals with K562 cells at room temperature for various times post-venipuncture. When data from six subjects were combined, the BCR-ABL/103 GUSB value trended down at 24h but was not significantly decreased until 48h (51% decrease, p = 0.004). To quantify the amount of whole blood RNA that can be loaded into an RT reaction without reducing RT efficiency, six different amounts of total RNA extracted from whole blood mixed with K562 cells were added into RT reactions. To measure RT efficiency, an RT Standards Mixture (RTSM) containing known copy numbers of External RNA Control Consortium (ERCC) 171 RNA and ERCC 113 cDNA was added to each RT reaction. RT efficiency was measured as the yield of PCR product from ERCC 171 RNA relative to ERCC 113 cDNA. Based on data from three subjects, compared to RT efficiency at reference concentration of 30 ng/µl RNA in RT, there was a 35% decrease (p = 0.043) at 167 ng/μl RNA and 82% reduction at 1000 ng/μl RNA. The maximum yield of BCR-ABL (molecules/μL cDNA) was observed at 300 ng/µl RNA/RT with a 3-fold increase (p=0.003) compared to 30 ng/µl RNA. Greater than 300 ng/µl RNA/RT did not further increase yield of BCR-ABL molecules/μL cDNA, likely due to reduced RT efficiency. We conclude that BCR-ABL/103 GUSB should be measured within 24 hours following blood collection. Because decreasing RT efficiency is associated with increasing RNA input into RT reactions, including 300 ng/µl RNA in RT reactions provides the maximum sensitivity in measuring BCR-ABL expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5538. doi:1538-7445.AM2012-5538
Scientific Foundations of Respiratory Medicine
Authors: David W. Cugell
Journal: JAMA (1982)

Because the content of this large volume is not apparent from the title, a brief description seems appropriate. The text is divided into the following seven sections: epidemiology, structure, normal physiology, biochemistry (and, in reality, considerable pharmacology), infection and host response, pathology and therapy, and disordered function. Each section contains from four to 12 chapters. It seems surprising that pulmonary immunology lacks a section of its own. However, with five separate chapters each dealing with a specific aspect of the immune response divided between two separate sections, the subject is not ignored. The editorial task of grouping the many chapters contributed by 62 different distinguished scientists is formidable. This book is in reality a compilation of up-to-date summaries, work-inprogress reports, and state-of-the-art presentations. It is for the serious student of pulmonary disease—readers interested in all of the major areas, including basic sciences, physical signs, pathophysiology, diagnosis, and treatment. Coverage of
UV-Radiation-Specific p53 Mutation Frequency in Normal Skin as a Predictor of Risk of Basal Cell Carcinoma
Authors: Allal Ouhtit, Hisayoshi Nakazawa, Hiroshi Yamasaki, Bruce K. Armstrong, Anne Kricker, Ernest Tan, Dallas R. English
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: A strong association has been found between skin cancer and exposure to UV radiation. The p53 tumor suppressor gene (also known as TP53), which is frequently mutated in human cancers, is believed to be an early target in UV radiation-associated skin carcinogenesis. We have previously developed a sensitive, polymerase chain reaction-based method capable of detecting and quantifying a UV radiation- specific mutation in the p53 gene (codons 247 and 248: AACCGG → AATTGG) in normal skin. We have used this method to examine whether UV radiation-specific mutation frequency is associated with risk of basal cell carcinoma (BCC) and with sun exposure. Methods: This case-control study in Australia involved 53 case subjects with BCC and 75 control subjects. DNA was isolated from normal skin (mirror-image anatomic site to the cancer site for case subjects and a randomly selected site for control subjects) and assayed for p53 mutation. Relationships between p53 mutation frequency and risk of BCC, sun sensitivity, or sun exposure were estimated by use of odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: Case subjects were more likely to have a p53 mutation than control subjects (OR = 3.1; 95% CI = 1.3–7.1). In addition, the odds of BCC increased monotonically with increasing frequency of p53 mutation. No statistically significant associations could be demonstrated between p53 mutation frequency and age, sex, sensitivity to the sun, pigmentary characteristics, total lifetime sun exposure, or sun exposure to the biopsy site. Conclusions: Our results indicate that tandem CC → TT mutations involving codons 247 and 248 of the p53 gene are associated with an increased risk of BCC but cannot be used as an accurate measure of total UV-radiation exposure.
Impact of Methicillin Resistance on Outcome of <i>Staphylococcus aureus</i> Ventilator-associated Pneumonia
Authors: Alain Combes, Charles-Edouard Luyt, Jean-Yves Fagon, Michel Wollf, Jean-Louis Trouillet, Claude Gibert, Jean Chastre
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The impact of methicillin resistance on morbidity and mortality of patients suffering from severe Staphylococcus aureus infections remains highly controversial. We analyzed a retrospective cohort of 97 patients with methicillin-susceptible and 74 patients with methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia (VAP). Initial empiric antibiotic therapy was appropriate for every patient. Patients with methicillin-resistant Staphylococcus aureus VAP were older, had higher disease-severity scores, and had been on mechanical ventilation longer at onset of VAP. Factors associated with 28-day mortality retained by multivariate logistic regression analysis were: age (odds ratio [OR] = 1.05, 95% confidence interval [CI], 1.02-1.08, p = 0.001) and Day 1 organ dysfunctions or infection (ODIN) score (OR = 1.90, 95% CI, 1.31-2.78, p = 0.001), but not methicillin resistance (OR = 1.72, 95% CI, 0.73-4.05, p = 0.22). The percentages of infection relapse or superinfection did not differ significantly between the two patient groups. In conclusion, after controlling for clinical and physiologic heterogeneity between groups, methicillin resistance did not significantly affect 28-day mortality of patients with Staphylococcus aureus VAP receiving appropriate antibiotics.
Activity and Risk of Coronary Heart Disease-Reply
Authors: Arthur S. Leon
Journal: JAMA (1988)

<h3>In Reply.</h3> —I agree that increased left ventricular mass in the presence of a compromised coronary artery supply may be detrimental. However, in experimental animals, increased left ventricular mass associated with exercise training is preceded and compensated for by increases in the cross-sectional area of the main coronary arteries, the coronary collateral blood supply, and the myocardial capillary density.<sup>1-3</sup>In monkeys, vascular adaptations to training seem to compensate for severe coronary atherosclerosis induced by diet.<sup>4</sup> In our Multiple Risk Factor Intervention Trial population, the physical fitness level of men in the most active tertile was only average for their age group, and those in the least active tertile were a little below average based on the results of treadmill exercise tests. In addition, only 4.7% of the study population reported an hour or more a week of heavy physical exertion, the threshold believed necessary to increase the cardiorespiratory
"MADURA FOOT" IN EGYPT.
Authors: ABDEL MONEM EL-MOFTY, I. O. ISKANDER, MOHAMED NADA, S. M. ZAKI
Journal: British Journal of Dermatology (1965)

Journal Article “MADURA FOOT” IN EGYPT. Get access ABDEL MONEM EL‐MOFTY, ABDEL MONEM EL‐MOFTY Professor of Dermatology Search for other works by this author on: Oxford Academic Google Scholar I. O. ISKANDER, M.D., I. O. ISKANDER, M.D. Professor of Dermatology Search for other works by this author on: Oxford Academic Google Scholar MOHAMED NADA, D.V.D., D.M., MOHAMED NADA, D.V.D., D.M. Consultant Dermatologist, Public Health Hospital Search for other works by this author on: Oxford Academic Google Scholar S. M. ZAKI, PH.D. S. M. ZAKI, PH.D. Microbiology, Faculty of Medicine, Cairo University Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 77, Issue 7, 1 July 1965, Pages 365–372, https://doi.org/10.1111/j.1365-2133.1965.tb14662.x Published: 01 July 1965
Effect of Neurolytic Celiac Plexus Block on Pain Relief, Quality of Life, and Survival in Patients With Unresectable Pancreatic Cancer
Authors: Gilbert Y. Wong, Darrell R. Schroeder, Paul E. Carns, Jack L. Wilson, David P. Martin, Michelle O. Kinney, Carlos B. Mantilla, David O. Warner
Journal: JAMA (2004)

Pancreatic cancer is an aggressive tumor associated with high mortality. Optimal pain control may improve quality of life (QOL) for these patients.To test the hypothesis that neurolytic celiac plexus block (NCPB) vs opioids alone improves pain relief, QOL, and survival in patients with unresectable pancreatic cancer.Double-blind, randomized clinical trial conducted at Mayo Clinic, Rochester, Minn. Enrolled (October 1997 and January 2001) were 100 eligible patients with unresectable pancreatic cancer experiencing pain. Patients were followed up for at least 1 year or until death.Patients were randomly assigned to receive either NCPB or systemic analgesic therapy alone with a sham injection. All patients could receive additional opioids managed by a clinician blinded to the treatment assignment.Pain intensity (0-10 numerical rating scale), QOL, opioid consumption and related adverse effects, and survival time were assessed weekly by a blinded observer.Mean (SD) baseline pain was 4.4 (1.7) for NCPB vs 4.1 (1.8) for opioids alone. The first week after randomization, pain intensity and QOL scores were improved (pain intensity, P< or =.01 for both groups; QOL, P<.001 for both groups), with a larger decrease in pain for the NCPB group (P =.005). From repeated measures analysis, pain was also lower for NCPB over time (P =.01). However, opioid consumption (P =.93), frequency of opioid adverse effects (all P>.10), and QOL (P =.46) were not significantly different between groups. In the first 6 weeks, fewer NCPB patients reported moderate or severe pain (pain intensity rating of > or =5/10) vs opioid-only patients (14% vs 40%, P =.005). At 1 year, 16% of NCPB patients and 6% of opioid-only patients were alive. However, survival did not differ significantly between groups (P =.26, proportional hazards regression).Although NCPB improves pain relief in patients with pancreatic cancer vs optimized systemic analgesic therapy alone, it does not affect QOL or survival.
England to launch special flu service next week to take pressure off primary care
Authors: Z. Kmietowicz
Journal: BMJ (2009)

The Department of Health for England has brought forward by three months its plans for a national pandemic flu service to relieve pressure on GPs and other NHS service providers as the number of cases of influenzaA/H1N1 and consultations continue to rise rapidly. The service, which will launch towards the end of the week, means that people will be able to get a prescription for antiviral drugs through a special telephone and internet service rather than by visiting or telephoning their GP.

England’s chief medical officer, Liam Donaldson, announced on 16 July that 26 people had died in England from swine flu, with another three deaths in Scotland, …