tbuckley/cabot-search huggingface dataset:
Targeting the Immunoregulator SRA/CD204 Potentiates Specific Dendritic Cell Vaccine-Induced T-cell Response and Antitumor Immunity
Authors: Huanfa Yi, Chunqing Guo, Xiaofei Yu, Ping Gao, Jie Qian, Daming Zuo, Masoud H. Manjili, Paul B. Fisher, John R. Subjeck, Xiang-Yang Wang
Journal: Cancer Research (2011)

Although dendritic cell (DC) vaccines offer promise as cancer immunotherapy, further improvements are needed to amplify their clinical therapeutic efficacy. The pattern recognition scavenger receptor SRA/CD204 attenuates the ability of DCs to activate CD8(+) T-cell responses. Therefore, we examined the impact of SRA/CD204 on antitumor responses generated by DC vaccines and we also evaluated the feasibility of enhancing DC vaccine potency by SRA/CD204 blockade. DCs from SRA/CD204-deficient mice were more immunogenic in generating antitumor responses to B16 melanoma, compared with DCs from wild-type mice. Similarly, siRNA-mediated knockdown of SRA/CD204 by lentiviral vectors improved the ability of wild-type DCs to stimulate the expansion and activation of CD8(+) T cells specific for idealized or established melanoma antigens in mice. Using SRA/CD204-silenced DCs to generate antigen-targeted vaccines, we documented a marked increase in the level of antitumor immunity achieved against established B16 tumors and metastases. This increase was associated with enhanced activation of antigen specific CTLs, greater tumor infiltration by CD8(+) T cells and NK cells, and increased intratumoral ratios of both CD4(+) and CD8(+) T-effector cells to CD4(+)CD25(+) T-regulatory cells. Our studies establish that downregulating SRA/CD204 strongly enhances DC-mediated antitumor immunity. In addition, they provide a rationale to enhance DC vaccine potency through SRA/CD204-targeting approaches that can improve clinical outcomes in cancer treatment.
Sequential Changes in Autonomic Regulation of Cardiac Myocytes after <i>In Vivo</i> Endotoxin Injection in Rat
Authors: NAJAH ABI-GERGES, BENOIT TAVERNIER, ALEXANDRE MEBAZAA, VALÉRIE FAIVRE, XAVIER PAQUERON, DIDIER PAYEN, RODOLPHE FISCHMEISTER, PIERRE-FRANÇOIS MÉRY
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We report that in vivo injection of endotoxin (EDTX, 6 mg · kg− 1) induces cardiovascular alterations in rats that closely mimic the clinical situation, as assessed by in vivo hemodynamic measurements in anesthetized and conscious, chronically instrumented animals. The patch-clamp technique was used to characterize the L-type calcium current (ICa) and its autonomic regulation in isolated cardiac myocytes. The density of ICa progressively decreased at 12 and 36 h after EDTX injection. However, the dihydropyridine ( ± )Bay K 8644 (100 nM) enhanced ICa to levels similar to those in control and EDTX-treated myocytes. In addition, the net stimulatory effect of a β -adrenergic agonist (isoproterenol) on ICa was increased 12 h after EDTX injection. This change in the β -adrenergic effect declined 24 h later. The potentiation in the β -adrenergic stimulation of ICa was mimicked by L858051 (10 μ M), a direct activator of adenylyl cyclase, but not by IBMX (200 μ M), a phosphodiesterase inhibitor. Besides, the antiadrenergic effect of acetylcholine on ICa was unchanged 12 h after EDTX injection, but increased 36 h after EDTX injection. These results support the hypothesis that time-dependent changes in the adenylyl cyclase pathway in cardiac myocytes may contribute, via the autonomic regulation of ICa, to the severity of myocardial dysfunction during sepsis.
THE SKIN REACTIONS PRODUCED BY ALTERNATIONS OF HEAT AND X-RAY AT VARIOUS TIME INTERVALS
Authors: James A. Hawkins
Journal: The Journal of Experimental Medicine (1931)

Areas on the abdomen of the same guinea pig were exposed to suberythemal doses of soft X-rays, to heat of an intensity below the critical dose for the production of burns, and to both radiations in sequence with various time intervals between the exposures. The only effect of exposure to X-ray or heat alone was a slight scaling of the skin. The areas exposed to heat and X-radiation developed well-marked and persistent burns when the exposure to one agent was made within 3 hours of the other. Scaling of the skin developed when the exposure to one agent was made 1 day after the other. This scaling was more marked and lasted longer than the scaling produced by either agent alone. The results were the same no matter in which sequence the agents were applied.
Clinical Features and Outcome in HIV-Associated Multicentric Castleman's Disease
Authors: Mark Bower, Tom Newsom-Davis, Kikkeri Naresh, Shairoz Merchant, Belinda Lee, Brian Gazzard, Justin Stebbing, Mark Nelson
Journal: Journal of Clinical Oncology (2011)

To describe clinical features, treatment outcomes and relapse rates in HIV-associated multicentric Castleman's disease (MCD) in a sizeable mature cohort.From a prospective database, we identified 61 HIV-seropositive patients with histologically confirmed MCD (median follow-up, 4.2 years). Since 2003, 49 patients with newly diagnosed MCD have been treated with rituximab with (n = 14) or without (n = 35) etoposide.At MCD diagnosis, 55 (90%) of 61 patients met proposed clinical criteria defining an attack. Four patients (7%) had histologic evidence of coexisting lymphoma, and one developed lymphoma 2 years after treatment. The incidence of lymphoma is 28 per 1,000 patient years. With rituximab-based treatment, the overall survival was 94% (95% CI, 87% to 100%) at 2 years and was 90% (95% CI, 81% to 100%) at 5 years compared with 42% (95% CI, 14% to 70%) and 33% (95% CI, 6% to 60%) in 12 patients treated before introduction of rituximab (log-rank P < .001). Four of 49 rituximab-treated patients have died; three died as a result of MCD within 10 days of diagnosis, and one died as a result of lymphoma in remission of MCD. Eight of 46 patients who achieved clinical remission suffered symptomatic, histologically confirmed MCD relapse. The median time to relapse was 2 years, and all have been successfully re-treated and are alive in remission. The 2- and 5-year progression-free survival rates for all 49 patients treated with rituximab-based therapy were 85% (95% CI, 74% to 95%) and 61% (95% CI, 40% to 82%), respectively.HIV-associated MCD is a remitting-relapsing disease. The outlook has improved dramatically in recent years with the introduction of rituximab-based therapy and yields high overall survival rates.
Ramifications of screening for breast cancer: 1 in 4 cancers detected by mammography are pseudocancers
Authors: H Gilbert Welch, Lisa M Schwartz, Steven Woloshin
Journal: BMJ (2006)

Ramifications of screening for breast cancerSee Research p 689 in 4 cancers detected by mammography are pseudocancersEditor-In this issue Zackrisson et al report on follow-up data from the Malmö mammographic screening trial and conclude that the rate of overdiagnosis of breast cancer was 10%. 1 They do not, however, calculate the risk we believe is most relevant to women considering mammography: What is the chance that a screen detected cancer represents overdiagnosis?After 15 years of follow-up, there were 1320 diagnosed in the screened group and 1205 in the control group (table 1).The excess detection of 115 cancers associated with screening led to their conclusion of an overdiagnosis rate of 10% (115/1205).However, because the intervention had stopped 15 years earlier and yet breast cancer cases continue to accumulate in both groups, the approach understates the risk of overdiagnosis.A more relevant denominator is the number of cancers found in the screened group at the end of the trial-741 (table 2).This addresses the question: Were I found to have cancer after being randomised to screening, how likely is it to represent overdiagnosis?As shown in the figure, using this denominator the risk of overdiagnosis is 15% (115/741).However, many of the cancers detected in the screened group are not detected by screening.They are instead clinically detected (either during the interval between screening examinations or among nonattenders).The most relevant denominator is the number of screen detected cancers found at the end of the trial.This addresses the question: Were I found to have cancer by a mammogram, how likely is it to represent overdiagnosis?Although this denominator is not reported by Zackrisson et al, the original BMJ article describing Malmö reported that 64% of the cancers detected in the screened group were detected by screening mammography. 2Thus one can deduce that the number of screen detected cancers at the end of the trial was about 475.As shown in the figure, using this denominator the risk of overdiagnosis is 24% (115/475).
Effect of lipids on growth hormone secretion in humans
Authors: William G. Blackard, Edgar W. Hull, Alfredo Lopez-S
Journal: Journal of Clinical Investigation (1971)

To determine the effect of elevations of plasma lipids on growth hormone secretion in humans, paired insulin hypoglycemia tests and paired arginine infusion tests were performed on eight and six normal female volunteers respectively. On 1 of the 2 test days for each growth hormone stimulus, subjects were given 60 g corn oil (Lipomul) 3 hr before testing followed by intravenous heparin (5000 U) at the time of insulin or arginine administration. Lipomul plus heparin administration inhibited both insulin- and arginine-induced plasma HGH elevations with almost complete suppression of the response to arginine. The plasma HGH (human growth hormone) inhibition was associated with elevation in plasma triglycerides and inhibition of plasma FFA (free fatty acid) depression after insulin or arginine. Neither the hypoglycemic response to insulin nor the blood glucose and plasma immunoreactive-insulin responses to arginine were altered by Lipomul plus heparin administration. In four additional subjects in whom Lipomul was given without heparin, the elevated plasma triglyceride values were not associated with suppression of arginine-induced plasma HGH elevations. In the same four subjects, heparin administration without Lipomul neither suppressed arginine-induced plasma HGH elevations nor prevented the depression in plasma FFA after arginine as much as when Lipomul plus heparin had been given. These latter observations suggest that the elevation in plasma FFA was responsible for suppression of growth hormone secretion by Lipomul plus heparin. These studies indicate a possible role of plasma FFA in regulation of growth hormone secretion.
Sirolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas: a Neurofibromatosis Clinical Trials Consortium phase II study
Authors: B. Weiss, B. C. Widemann, P. Wolters, E. Dombi, A. Vinks, A. Cantor, J. Perentesis, E. Schorry, N. Ullrich, D. H. Gutmann, J. Tonsgard, D. Viskochil, B. Korf, R. J. Packer, M. J. Fisher
Journal: Neuro-Oncology (2014)

Plexiform neurofibromas (PNs) are benign peripheral nerve sheath tumors that arise in one-third of individuals with neurofibromatosis type 1 (NF1). They may cause significant disfigurement, compression of vital structures, neurologic dysfunction, and/or pain. Currently, the only effective management strategy is surgical resection. Converging evidence has demonstrated that the NF1 tumor suppressor protein, neurofibromin, negatively regulates activity in the mammalian Target of Rapamycin pathway. We employed a 2-strata clinical trial design. Stratum 1 included subjects with inoperable, NF1-associated progressive PN and sought to determine whether sirolimus safely and tolerably increases time to progression (TTP). Volumetric MRI analysis conducted at regular intervals was used to determine TTP relative to baseline imaging. The estimated median TTP of subjects receiving sirolimus was 15.4 months (95% CI: 14.3–23.7 mo), which was significantly longer than 11.9 months (P < .001), the median TTP of the placebo arm of a previous PN clinical trial with similar eligibility criteria. This study demonstrated that sirolimus prolongs TTP by almost 4 months in patients with NF1-associated progressive PN. Although the improvement in TTP is modest, given the lack of significant or frequent toxicity and the availability of few other treatment options, the use of sirolimus to slow the growth of progressive PN could be considered in select patients.
Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica
Authors: Julian Parkhill, Mohammed Sebaihia, Andrew Preston, Lee D Murphy, Nicholas Thomson, David E Harris, Matthew T G Holden, Carol M Churcher, Stephen D Bentley, Karen L Mungall, Ana M Cerdeño-Tárraga, Louise Temple, Keith James, Barbara Harris, Michael A Quail, Mark Achtman, Rebecca Atkin, Steven Baker, David Basham, Nathalie Bason, Inna Cherevach, Tracey Chillingworth, Matthew Collins, Anne Cronin, Paul Davis, Jonathan Doggett, Theresa Feltwell, Arlette Goble, Nancy Hamlin, Heidi Hauser, Simon Holroyd, Kay Jagels, Sampsa Leather, Sharon Moule, Halina Norberczak, Susan O'Neil, Doug Ormond, Claire Price, Ester Rabbinowitsch, Simon Rutter, Mandy Sanders, David Saunders, Katherine Seeger, Sarah Sharp, Mark Simmonds, Jason Skelton, Robert Squares, Steven Squares, Kim Stevens, Louise Unwin, Sally Whitehead, Bart G Barrell, Duncan J Maskell
Journal: Nature Genetics (2003)
Long-term follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma
Authors: Luisa Giaccone, Barry Storer, Francesca Patriarca, Marcello Rotta, Roberto Sorasio, Bernardino Allione, Fabrizio Carnevale-Schianca, Moreno Festuccia, Lucia Brunello, Paola Omedè, Sara Bringhen, Massimo Aglietta, Alessandro Levis, Nicola Mordini, Andrea Gallamini, Renato Fanin, Massimo Massaia, Antonio Palumbo, Giovannino Ciccone, Rainer Storb, Ted A. Gooley, Mario Boccadoro, Benedetto Bruno
Journal: Blood (2011)
Gene-Lifestyle Interaction and Type 2 Diabetes: The EPIC InterAct Case-Cohort Study
Authors: Claudia Langenberg, Stephen J. Sharp, Paul W. Franks, Robert A. Scott, Panos Deloukas, Nita G. Forouhi, Philippe Froguel, Leif C. Groop, Torben Hansen, Luigi Palla, Oluf Pedersen, Matthias B. Schulze, Maria-Jose Tormo, Eleanor Wheeler, Claudia Agnoli, Larraitz Arriola, Aurelio Barricarte, Heiner Boeing, Geraldine M. Clarke, Françoise Clavel-Chapelon, Eric J. Duell, Guy Fagherazzi, Rudolf Kaaks, Nicola D. Kerrison, Timothy J. Key, Kay Tee Khaw, Janine Kröger, Martin Lajous, Andrew P. Morris, Carmen Navarro, Peter M. Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, J. Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, María-José Sánchez, Nadia Slimani, Annemieke M. W. Spijkerman, Rosario Tumino, Daphne L. van der A, Yvonne T. van der Schouw, Inês Barroso, Mark I. McCarthy, Elio Riboli, Nicholas J. Wareham
Journal: PLoS Medicine (2014)

In this study, Wareham and colleagues quantified the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. The authors found that the relative effect of a type 2 diabetes genetic risk score is greater in younger and leaner participants, and the high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention. Please see later in the article for the Editors' Summary
The Adenocarcinoma-Associated Antigen, <i>AGR2</i>, Promotes Tumor Growth, Cell Migration, and Cellular Transformation
Authors: Zheng Wang, Ying Hao, Anson W. Lowe
Journal: Cancer Research (2008)

The AGR2 gene encodes a secretory protein that is highly expressed in adenocarcinomas of the esophagus, pancreas, breast, and prostate. This study explores the effect of AGR2 expression with well-established in vitro and in vivo assays that screen for cellular transformation and tumor growth. AGR2 expression in SEG-1 esophageal adenocarcinoma cells was reduced with RNA interference. Cellular transformation was examined using NIH3T3 cells that express AGR2 after stable transfection. The cell lines were studied in vitro with assays for density-dependent and anchorage-independent growth, and in vivo as tumor xenografts in nude mice. SEG-1 cells with reduced AGR2 expression showed an 82% decrease in anchorage-independent colony growth and a 60% reduction in tumor xenograft size. In vitro assays of AGR2-expressing NIH3T3 cells displayed enhanced foci formation and anchorage-independent growth. In vivo, AGR2-expressing NIH3T3 cells established tumors in nude mice. Thus, AGR2 expression promotes tumor growth in esophageal adenocarcinoma cells and is able to transform NIH3T3 cells. Immunohistochemistry of the normal mouse intestine detected AGR2 expression in proliferating and differentiated intestinal cells of secretory lineage. AGR2 may be important for the growth and development of the intestine as well as esophageal adenocarcinomas.
A CASE OF DERMATITIS HERPETIFORMIS
Authors: J. L. BUNCH
Journal: British Journal of Dermatology (1912)

Journal Article A CASE OF DERMATITIS HERPETIFORMIS Get access J. L. BUNCH, D.Sc., M.D. J. L. BUNCH, D.Sc., M.D. Physician to the Skin‐Department, Queen's Hospital for Children Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 24, Issue 8, 1 August 1912, Pages 311–312, https://doi.org/10.1111/j.1365-2133.1912.tb16738.x Published: 01 August 1912
Circadian rhythms of nocturnal hormones in rheumatoid arthritis: translation from bench to bedside
Authors: M. Cutolo, R. H Straub, F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2008)

Translation from basic research to clinical medicine is complex and needs to be carefully performed. In addition, translational research is needed using human subjects who meet current diagnostic criteria.

Recently, circadian rhythm science has pointed the way to rational intervention on nocturnal hormone production to modulate the immune/inflammatory reactions in patients suffering from rheumatoid arthritis (RA).1 2 These approaches have been introduced into practice with increasing degrees of interest.3

We will discuss two recent examples of therapeutically modulating melatonin (MLT) and cortisol as nocturnal hormones implicated in RA clinical circadian rhythms.

It has been known for many decades that disease symptoms in RA follow obvious circadian rhythms, with an increase of activity in the early morning hours, abatement during the day, and a smaller new increase in the early evening (fig 1A).3 4



Figure 1 Circadian rhythm of symptoms and interleukin (IL)-6. A. The graph depicts the circadian rhythm of joint stiffness, pain and functional disability. B. The circadian rhythm of IL6 secretion in healthy subjects (black line) and patients with rheumatoid arthritis (red line). The data are given as percentages of the 24-h mean value of the respective variable.

A number of papers have reported a temporal relationship between elevated levels of pro-inflammatory cytokines and symptoms of RA, such as morning stiffness. 4–9 Several of these cytokines are highly elevated in patients with active RA in the early hours of the day but after noon they are almost non-existent. Their release pattern and serum concentrations, respectively—possibly triggered by MLT and other hormones or a subordinate neuroendocrine centre in the hypothalamus4—follow a strict 24-h daily cycle (fig 1B).

The closest similarity with the daily pattern of RA symptoms, such as morning stiffness, joint pain and functional disability, seems to exist for interleukin (IL)-6.

Pro-inflammatory hormones start to rise before the onset of RA symptoms and before endogenous cortisol in these patients is activated to counteract the inflammatory cascade of disease symptoms. It should be also noted that rhythmic fluctuations of the nocturnal secretion and the peripheral metabolism of endogenous cortisol, as well as changes in the activation of …
Relation between foot arch index and ankle strength in elite gymnasts: a preliminary study
Authors: S T Aydog, L Özçakar, O Tetik, H A Demirel, Z Hasçelik, M N Doral
Journal: British Journal of Sports Medicine (2005)

Background: Gymnasts usually start intensive training from early childhood. The impact of such strenuous training on the musculoskeletal system is not clear. Objectives: To evaluate the relation between muscle strength of the ankle joint and foot structure in gymnasts. Methods: The study population comprised 20 high level male gymnasts and 17 non-athletic healthy male controls. Arch indices were measured using a podoscope. Ankle plantar/dorsiflexion and eversion/inversion strengths were measured using a Biodex 3 dynamometer within the protocol of concentric/concentric five repetitions at 30°/s velocity. Results: The mean arch index of the right and left foot of the gymnasts and the controls were respectively: 31.4 (29.1), 34.01 (34.65); 60.01 (30.3), 63.75 (32.27). Both the arch indices and the ankle dorsiflexion strengths were lower in the gymnasts. Although no correlation was found between strength and arch index in the control group, a significant correlation was observed between eversion strengths and arch indices of the gymnasts ( r = 0.41, p = 0.02). Conclusions: Whether or not the findings indicate sport specific adaptation or less training of the ankle dorsiflexors, prospective data are required to elucidate the tendency for pes cavus in gymnasts, for whom stabilisation of the foot is a priority.
FROM MEASURING TO IMPROVING PUBLIC HEALTH PRACTICE
Authors: Bernard J. Turnock, Arden S. Handler
Journal: Annual Review of Public Health (1997)

▪ Abstract Efforts to measure public health practice have taken on various forms and focused on different aspects of the system of public health practice over the past century. Before 1990, measurement was primarily based on a series of self-assessment instruments initiated under the auspices of the Committee on Administrative Practice of the American Public Health Association. These instruments emphasized measurement of immediate results of local public health services although they also provided information on local resources and capacity to perform. Following the Institute of Medicine's report in 1988, efforts began to focus on performance related to public health's core functions. These more recent assessments suggest that the system of public health practice must be improved to achieve the targets of effectiveness established for the year 2000. Ultimately, a comprehensive national surveillance system for public health practice will need to both measure and examine the relationships among inputs (resources, capacity, etc), core function–related processes, outputs (services) as well as outcomes.