tbuckley/cabot-search huggingface dataset:
Vaccination of patients with primary Sjogren's syndrome reveals hyperreactive B cell compartment with a skewed maturation pattern
Authors: S. Brauner, M. Kvarnstom, S. Gorgen, M. Franzen-Malmros, K. A. Brokstad, L. Folkersen, C. Trollmo, L. Klareskog, R. Jonsson, V. Malmstrom, M. Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Multiple immune disturbances underlying disease development and progression have been implicated in primary Sjögren9s syndrome (pSS), especially defects in the B cell compartment. In this study we used vaccination as a tool to analyse defects in immune regulation in vivo in individuals with pSS, and specifically to characterise B cell development and responses. <h3>Methods</h3> Fourteen SSA positive women with pSS and 18 gender and age matched healthy controls were vaccinated against H1N1 influenza with a priming dose and booster 3 weeks apart. Blood samples were obtained before injections and after 1 and 3 weeks. Total Ig-levels and vaccine specific responses were analysed by ELISPOT, ELISA and hemagglutination tests. Lymphocyte phenotypes were characterised by flow cytometry and clinical routine laboratory tests were performed. Serum cytokine levels and microarray-based RNA expression analysis was performed, as well as genotyping for selected markers. Clinical parameters and potential adverse reactions were monitored with a clinical questionnaire. <h3>Results</h3> All subjects developed protective immunity to H1N1 influenza upon vaccination with a similar adverse effect profile. However, when dissecting the vaccine specific response patients developed significantly higher titers of IgG vaccine specific antibodies and significantly lower IgM titers. Interestingly, the IgG antibodies were of higher avidity, indicating that this was a specific response. In addition, hypergammaglobulinemia was induced in the patients and anti-SSA/Ro52 titers were transiently elevated. No significant phenotypic differences were observed in the lymphocyte compartment at the start of the study, but already 1 week after the first vaccination pSS patients had significantly fewer CD19 class switched B cells and more immature B cells in circulation. This skewed pattern of B cell maturation remained throughout the study. Paradoxically, plasmablasts appeared at a significantly higher level in patients after immunisation. In accordance, significantly higher levels of several pro-inflammatory cytokines (IL-6, IL-10, IL-12p40 and TNFα), as well as the B cell promoting cytokines IL-7 and BAFF were induced upon vaccination in the patients. Microarray analysis revealed an interferon-signature in the patients. <h3>Conclusions</h3> Patients with Sjögren9s syndrome respond to vaccination with protective immunity. However, the induced IgG vaccine-specific antibodies are of significantly higher titers and of stronger avidity than in healthy controls, occuring in parallel with a skewed B cell maturation and induction of a pro-inflammatory cytokine response. This may reflect the mechanisms allowing high titers of autoantibodies to develop in pSS patients.
Predicting Nutrient Deficiency by Formula
Authors: Victor Herbert
Journal: New England Journal of Medicine (1971)

Almost a decade ago, it was noted, in the issue of Archives of Internal Medicine honoring Maxwell Finland, that the minimal adult requirement for folic acid to sustain normality was in the range of 50 μg daily.1 It was stated that, "Dividing the 4 1/2 months required for a healthy normal adult male to develop megaloblastic anemia on a diet containing approximately 5 μg of folate per day into the figure of 7.5 mg (Ed. note: based on the middle class New England adult male "average" tissue folate store of 7.5 ± 2.5 mg) one arrives at a rough . . .
Time to legalise assisted dying?: RCGP is not neutral: it opposes a change in legislation
Authors: Mayur K Lakhani
Journal: BMJ (2005)

EDITOR—Delamothe states that the Royal College of General Practitioners (RCGP) has a neutral stance on the issue of assisted dying.1 This is no longer correct.

At a meeting of the college council in June 2005 it was decided, by a …
Interarticular Dislocation of the Patella
Authors: Cornelius N. Stover
Journal: JAMA (1967)

DISLOCATION of the patella into the interarticular space is apparently rare, but as so often the case, optimum treatment depends upon one's awareness of this injury. Brady and Russell,<sup>1</sup>in a recent review of the literature, were able to collect 25 cases. To this group they added one of their own, and concluded that closed manipulation was rarely, if ever, successful. They advised prompt open reduction. The following case report supports this contention. <h3>Report of a Case</h3> A 12-year-old white boy was struck by a car while riding his bicycle on the evening of Aug 30, 1963. He sustained injury to his left shoulder and his right knee. He was taken to a nearby hospital where roentgenographic examination revealed an undisplaced fracture of the surgical neck of the right humerus and an interarticular dislocation of the right knee (Figure). These x-ray films showed the patella rotated 90° about its
Radiation as the Cause of Lung Cancer among Uranium Miners
Authors: Joseph K. Wagoner, Victor E. Archer, Frank E. Lundin, Duncan A. Holaday, J. William Lloyd
Journal: New England Journal of Medicine (1965)

THE identification of etiologic agents in chronic-disease epidemiology depends on sound study design, rigorous analytical methods and definitive criteria for evaluation. Unfortunately, the implementation of these principles has been all too infrequent in the field of occupational carcinogenesis. It is not surprising, therefore, that occupational studies on the same suspect carcinogen have often resulted in conflicting conclusions.A case in point is the lack of unanimity concerning the role of airborne radiation as an occupational carcinogen in man. This controversy dates from 1879, when Härting and Hesse1 first made note of the strikingly high percentage of deaths from pulmonary neoplasia . . .
Doctor is struck off for failing to disclose manslaughter conviction in Spain
Authors: C. Dyer
Journal: BMJ (2012)

A doctor who was convicted of manslaughter in Spain for ending the life of a terminally ill patient but who concealed that he was under investigation for the crime when he came to the United Kingdom to work has been ordered to be struck off the UK medical register.

Marcos Hourmann, originally from Argentina, was backed by the son and daughter of 82 year old Carmen Cortiella, who had advanced colon cancer, diabetes, and hypertension and had had a heart attack, but he was convicted of her manslaughter in Spain in 2009.

A General Medical Council fitness to practise panel has ordered him to be struck off …
Multiscale modeling of brain dynamics depends upon approximations at each scale
Authors: J. J. Wright, D. T. J. Liley
Journal: Behavioral and Brain Sciences (1996)

Abstract We outline fresh findings that show that our macroscopic electrocorticographic (ECoG) simulations can account for synchronous multiunit pulse oscillations at separate, simultaneously activated cortical sites and the associated gamma-band ECoG activity. We clarify our views on the approximations of dynamic class applicable to neural events at macroscopic and microscopic scales, and the analogies drawn to classes of ANN behaviour. We accept the need to introduce memory processes and detailed anatomical and physiological information into any future developments of our simulations. On the issue of intrinsic cortical stability and the role of extrinsic fibre systems in maintaining stability, we argue that this position is not in extreme contradiction to those of our commentators, and that the mechanisms implicit in our simulations' properties imply rich computational possibilities. We discuss some of the reasons for and against the existence of significant global resonances in the brain and explain why such behaviour appears absent in our simulations. Last, we discuss other phenomena, such as rhythmic driving of the cortex, which have not yet been introduced into our models, and indicate lines for future development of the simulations.
A comparative evaluation of poly-l-lysine-palmitic acid and Lipofectamine ™ 2000 for plasmid delivery to bone marrow stromal cells
Authors: Başak Açan Clements, Vanessa Incani, Cezary Kucharski, Afsaneh Lavasanifar, Bruce Ritchie, Hasan Uludağ
Journal: Biomaterials (2007)
Abstract 2408: Selective delivery of NY-ESO-1 antigen protein by cholesteryl pullulan (CHP) to CD8α+ dendritic cells in the draining lymph node for cross-presentation
Authors: Naozumi Harada, Daisuke Muraoka, Kazuo Tajima, Hiroshi Shiku
Journal: Cancer Research (2010)

Abstract Exogenous protein antigens per se poorly stimulate CD8+ T cells when used as immunogens. Hence, this could be a major drawback of cancer vaccines with protein antigens. To overcome the problem, we developed cholesteryl pullulan (CHP) as a delivery system for protein antigens. A series of in vitro and in vivo experiments and clinical studies confirmed that a therapeutic cancer vaccine containing the complex of CHP and protein antigen such as NY-ESO-1 or HER2 efficiently stimulated not only CD4+ T cells but also CD8+ T cells. To understand the mechanism underlying such effect of CHP, we investigated the tissue distribution of NY-ESO-1 protein complexed with CHP (CHP-NY-ESO-1) after its subcutaneous injection into mice by tracing the protein using NY-ESO-1-specific sandwich ELISA or FACS analysis with fluorescently labeled protein. By sandwich ELISA, NY-ESO-1 protein was detected only in the skin at the injection site, and its content was significantly higher with CHP-NY-ESO-1 than with NY-ESO-1 alone, indicating that CHP would make NY-ESO-1 protein antigen more persistent in vivo. In FACS analysis, fluorescence-positive cells which incorporated NY-ESO-1 protein were detected only in the draining lymph node among the lymphoid tissues such as draining/non-draining lymph nodes, spleen and peripheral blood mononuclear cells. Interestingly, the percentage of fluorescence-positive cells in the whole lymphocytes of this tissue was much higher with CHP-NY-ESO-1 (6.4%) than with NY-ESO-1 alone (0.9%). The lymphocytes capably incorporated fluorescence were CD11b+ cells and CD11c+ cells that include professional antigen-presenting cells such as macrophages and dendritic cells, respectively. In the mice received CHP-NY-ESO-1, the percentages of fluorescence-positive CD11b+ cells and CD11c+ cells were 53% and 66% at the highest, respectively, while these values in the mice with NY-ESO-1 alone were around 10%. Among the CD11c+ cells, as well as other dendritic cell subsets, the fluorescence was detected in the CD8α+ cells which are known to be capable to efficiently cross-present protein antigens. These results suggest that CHP would be an “immunotransporter” which efficiently delivers protein antigens to the antigen-presenting cells in draining lymph nodes. Hence, CHP may facilitate the presentation of protein antigens to both CD8+ T cells and CD4+ T cells. 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 2408.
Plasma cells require autophagy for sustainable immunoglobulin production
Authors: Niccolò Pengo, Maria Scolari, Laura Oliva, Enrico Milan, Federica Mainoldi, Andrea Raimondi, Claudio Fagioli, Arianna Merlini, Elisabetta Mariani, Elena Pasqualetto, Ugo Orfanelli, Maurilio Ponzoni, Roberto Sitia, Stefano Casola, Simone Cenci
Journal: Nature Immunology (2013)
Abstract 260: CD44 isoform specificity in controlling breast tumor initiating cell properties.
Authors: Rhonda L. Brown, Sali Liu, Lauren M. Reinke, Chonghui Cheng
Journal: Cancer Research (2013)

Abstract Tumor initiating cells (TICs) constitute a small fraction of tumor cells that display stem cell characteristics, including the ability to self-renew and generate heterogeneous tumors. A CD44+/CD24- profile has been widely used to identify TICs in a variety of tumors. However, it has remained unknown whether CD44 is functionally required for TICs and whether a specific CD44 isoform is enriched in TICs. Here, we report that the CD44s isoform is the major splice isoform expressed in a CD44+/CD24- breast stem cell population. Functionally, CD44s is required for expression of a breast stem cell (BSC) gene signature and is essential for mammosphere formation. Modulation of CD44 alternative splicing by the splicing regulator ESRP1 prevents CD44s production and, in turn, inhibits mammosphere formation and expression of the BSC signature. Furthermore, CD44s is required for limiting numbers of TICs to form tumors in an animal model of breast cancer progression. Together, these data illustrate that the CD44s splice isoform is enriched in CD44+/CD24- breast stem cells and serves as an important regulator of stem cell properties. Our results also suggest that CD44s-dependent TIC properties can be controlled at the level of alternative splicing by splicing factors that regulate production of specific CD44 isoforms. Citation Format: Rhonda L. Brown, Sali Liu, Lauren M. Reinke, Chonghui Cheng. CD44 isoform specificity in controlling breast tumor initiating cell properties. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 260. doi:10.1158/1538-7445.AM2013-260 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Role of adenosine in pathogenesis of anginal pain.
Authors: F Crea, G Pupita, A R Galassi, H el-Tamimi, J C Kaski, G Davies, A Maseri
Journal: Circulation (1990)

The intravenous infusion of adenosine provokes anginalike chest pain. To establish its origin, an intracoronary infusion of increasing adenosine concentrations was given in 22 patients with stable angina pectoris. During adenosine infusion, 20 patients had chest pain without electrocardiographic signs of ischemia. They all reported that the chest pain was similar to their usual anginal pain. In 10 of the 22 patients adenosine was also infused into the right atrium, but it never produced symptoms at the doses that had provoked chest pain during intracoronary infusion. In seven other patients, the intracoronary adenosine infusion was repeated after intravenous administration of aminophylline, an antagonist of adenosine P1-receptors. Aminophylline decreased the severity of adenosine-induced chest pain (assessed with a visual analog scale) from 42 +/- 22 to 23 +/- 17 mm (p less than 0.002). In the remaining five of the 22 patients, monitoring of blood oxygen saturation in the coronary sinus during intracoronary adenosine administration showed that maximum coronary vasodilation was achieved at doses lower than those responsible for chest pain. A single-blind, placebo-controlled, randomized trial of the effect of aminophylline on exercise-induced chest pain was also performed in 20 other patients with stable angina. Aminophylline, compared with placebo, decreased the severity of chest pain at peak exercise from 67 +/- 21 to 51 +/- 23 mm (p less than 0.02), despite the achievement of a similar degree of ST-segment depression. Finally, the effect of intravenous adenosine was compared in 10 patients with predominantly painful myocardial ischemia and in 10 patients with predominantly silent ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Health effects of acid aerosols on North American children: pulmonary function.
Authors: M Raizenne, L M Neas, A I Damokosh, D W Dockery, J D Spengler, P Koutrakis, J H Ware, F E Speizer
Journal: Environmental Health Perspectives (1996)

We examined the health effects of exposure to acidic air pollution among children living in 24 communities in the United States and Canada. Parents of children between the ages of 8 and 12 completed a self-administered questionnaire and provided consent for their child to perform a standardized forced expiratory maneuver at school in 22 of these communities. Air quality and meteorology were measured in each community for the year preceding the pulmonary function tests. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1.0) measurements of 10,251 white children were examined in a two-stage regression analysis that adjusted for age, sex, height, weight, and sex-height interaction. In this study, a 52 nmol/m3 difference in annual mean particle strong acidity was associated with a 3.5% (95% CI, 2.0-4.9) decrement in adjusted FVC and a 3.1% (95% CI, 1.6-4.6) decrement in adjusted FEV1.0. The FVC decrement was larger, although not significantly different, for children who were lifelong residents of their communities (4.1%, 95% CI, 2.5-5.8). The relative odds for low lung function (that is, measured FVC less than or equal to 85% of predicted), was 2.5 (95% CI, 1.8-3.6) across the range of particle strong acidity exposures. These data suggest that long-term exposure to ambient particle strong acidity may have a deleterious effect on lung growth, development, and function.
Incidence of Anticonvulsant Osteomalacia and Effect of Vitamin D: Controlled Therapeutic Trial
Authors: C. Christiansen, P. Rodbro, M. Lund
Journal: BMJ (1973)

The bone mineral content (B.M.C.) in both forearms (related to total body calcium) was measured by photon absorptiometry for a controlled therapeutic trial in a representative sample of epileptic outpatients, comprising 226 patients treated with one or two major anticonvulsant drugs (phenytoin, phenobarbitone, primidone). Initially the mean B.M.C. value for all epileptic patients was 87% of normal. During treatment with 2,000 international units of vitamin D<sub>2</sub> daily for three months an average B.M.C. increase of 4% was found, whereas the B.M.C. values remained unchanged in the placebo group and in the control groups. The incidence of hypocalcaemia and raised serum alkaline phosphatase was 12% and 43% respectively. The biochemical indices of osteomalacia were related to B.M.C. These results indicate that epileptic patients should be closely supervised for the occurrence of anticonvulsant osteomalacia, and, possibly, receive prophylactic treatment with vitamin D.
Matthias Rath drops libel action against Guardian
Authors: S. Boseley
Journal: BMJ (2008)

Matthias Rath, a doctor who promoted nutritional supplements to people with HIV in South Africa and argued that antiretroviral drugs were harmful, has dropped a year long libel case against the Guardian newspaper and been ordered to pay costs.

Dr Rath, a German born doctor who once worked in California on the possible therapeutic effects of micronutrients with the Nobel prize winner Linus Pauling and claimed to be his nominated successor, sued the newspaper over three articles written by Ben Goldacre in his column Bad Science.

In articles published in January and February last year, Dr Goldacre described Dr Rath (not the only promoter of unproved nutritional therapies in a South Africa where the government …
Infectious Hepatitis
Authors: Robert Ward, Saul Krugman, Joan P. Giles, A. Milton Jacobs, Oscar Bodansky
Journal: New England Journal of Medicine (1958)

THE control of viral hepatitis in both military and civilian populations presents one of the foremost problems in preventive medicine. The adaptation of the etiologic agent or agents to a laboratory animal or to tissue culture and the development of a specific immunologic test would provide tools to speed the solution of the problem. Neither tool is available at present. Man still remains the only established susceptible host. The clinical diagnosis of viral hepatitis is aided by certain practical tests of liver function. These tests are not specific, and possibly are of little value in revealing subclinical cases, which may . . .
Dermoscopic Evaluation of Nodular Melanoma
Authors: Scott W Menzies, Fergal J Moloney, Karen Byth, Michelle Avramidis, Giuseppe Argenziano, Iris Zalaudek, Ralph P Braun, Josep Malvehy, Susana Puig, Harold S Rabinovitz, Margaret Oliviero, Horacio Cabo, Riccardo Bono, Maria A Pizzichetta, Magdalena Claeson, Daniel C Gaffney, H Peter Soyer, Ignazio Stanganelli, Richard A Scolyer, Pascale Guitera, John Kelly, Olivia McCurdy, Alex Llambrich, Ashfaq A Marghoob, Pedro Zaballos, Herbert M Kirchesch, Domenico Piccolo, Jonathan Bowling, Luc Thomas, Karin Terstappen, Masaru Tanaka, Giovanni Pellacani, Gianluca Pagnanelli, Giovanni Ghigliotti, Blanca Carlos Ortega, Greg Crafter, Ana María Perusquía Ortiz, Isabelle Tromme, Isil Kilinc Karaarslan, Fezal Ozdemir, Anthony Tam, Christian Landi, Peter Norton, Nida Kaçar, Lidia Rudnicka, Monika Slowinska, Olga Simionescu, Alessandro Di Stefani, Elliot Coates, Juergen Kreusch
Journal: JAMA Dermatology (2013)

Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical.To determine the dermoscopy features of NM.Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes.Predominantly hospital-based clinics from 5 continents.Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma.Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM.When a progressively growing, symmetrically patterned melanocytic nodule is identified, NM needs to be excluded.
Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila
Authors: Brenda Cohen, Arash Bashirullah, Lina Dagnino, Christine Campbell, William W. Fisher, Ching Ching Leow, Elisabeth Whiting, David Ryan, Dawn Zinyk, Gabrielle Boulianne, Chi-chung Hui, Brenda Gallic, Robert A. Phillips, Howard D. Lipshitz, Sean E. Egan
Journal: Nature Genetics (1997)