tbuckley/cabot-search huggingface dataset:
PMO-088 A large proportion of colorectal tumour-infiltrating CD4+ T cells are suppressive irrespective of FOXP3 expression
Authors: M Scurr, A Gallimore, A Godkin
Journal: Gut (2012)

<h3>Introduction</h3> The presence of increased numbers of CD3<sup>+</sup> T cells in colorectal cancer (CRC) correlates with improved prognosis. However, it is difficult to measure anti-tumour responses in tumour-infiltrating lymphocytes (TILs) suggesting these cells are suppressed. Although we have demonstrated CD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells (Tregs) within the tumour and its stroma, the numbers are often low. We sought to identify phenotypic and functional characteristics of CD4<sup>+</sup>Foxp3<sup>−</sup> T cells to determine whether other regulatory populations exist within this environment. <h3>Methods</h3> Tumour samples were obtained from CRC patients with different stages of malignancy. Fixed tumour samples were examined by immunofluoresence for CD3, CD8 and FoxP3. TILs from fresh tumour tissue were stained with a panel of 20 antibodies (including Helios, LAG-3, LAP) and examined by FACS. <h3>Results</h3> Histology revealed tumours to be infiltrated by CD4<sup>+</sup>, CD8<sup>+</sup> and Foxp3<sup>+</sup> positive cells. Despite an increase in CD4<sup>+</sup> and CD8<sup>+</sup> T cells in advanced tumours, there was not always a concomitant increase in Foxp3<sup>+</sup> cells. Flow cytometry revealed the majority of the Treg fraction was Helios<sup>+</sup> (indicating thymically-derived) and expressed higher levels of CTLA-4 and CD39 than Tregs from colon and blood. However, 30% of “conventional” CD4<sup>+</sup>Foxp3<sup>−</sup> T cells express markers associated with Tregs including LAP (latency-associated peptide), LAG-3 and CD25 and were highly suppressive in vitro. <h3>Conclusion</h3> Tumour-infiltrating CD4<sup>+</sup> T cells are heterogeneous. A high percentage of these cells appear to have a regulatory function and include both Foxp3<sup>+</sup> as well as FoxP3<sup>−</sup> T cells. Overcoming the suppressive environment of CRC is a major challenge for boosting anti-tumour immunity. <h3>Competing interests</h3> None declared.
Clinical Management of Total Artificial Heart Drive Systems
Authors: J B Mays, M A Williams, L E Barker, M A Pfeifer, J M Kammerling, S Y Jung, W C DeVries
Journal: JAMA (1988)

THE EVOLUTION of the total artificial heart (TAH) from animal experimentation to clinical research has necessitated major changes in the control of the drive equipment responsible for prosthesis function. Our experience with patients who have been permanent recipients of the heart has contributed to a refinement of the operating protocol and furthered understanding of the hemodynamic response to artificial circulation devices. <h3>PROSTHESIS DESIGN</h3> The basic design of the pneumatic TAH has changed little since early animal experimentation and still incorporates a flexible diaphragm inside a semirigid housing.<sup>1-3</sup>In the Jarvik-7-100 (Symbion, Inc, Salt Lake City) ventricles, which constitute the device under discussion herein, polyurethane polymer (Biomer, Ethicon Inc, Somerville, NJ) is molded with Dacron polyester mesh to form the semirigid housing. Four layers of Biomer each 0.18 mm in thickness constitute the inflatable diaphragm. Graphite powder between the diaphragm layers deters creation of a flexion crease, which could lead
Remarks on Death following Enucleation of the Eye-Ball
Authors: A. H. Griffith
Journal: BMJ (1884)

IN bringing before you the subject' of death following enucleation of the eyeball, I have done so with the 'object of making, known the details of two fatal cases observed at the Manchester Royal Eye [Hospital, and of getting the opinions of the members present in regard to certain points in connection with this subject.CASE i.-The fiTst case was that of an old man, aged 71, under the care of Dr. Glascott, who was admitted for the excision of a rodent ulcer occurring in the lids of the right eye, the globe itself being atrophied.Excision of the globe was performed as a preliminary step on July 28th, 1881.Chloroform was-administered, and there 'was noth- ing of unusual occurrence in the performance'of the operation.He never rallied from the effects of the operation, but died on the' sixth day after exhibiting undoubted symptois of menIngitis, CASE ii.-The second case was that of a woman, aged 48, who %vis admitted under Dr. Mules, with the right eye in a state of panophthalmitis.She was suffering considerably from the pain caused by this
THU0482 Assesment Life Quality of Familial Mediterranean Fever Patients by Short Form–36 and Its Relationship with Disease Parameters
Authors: S. Senel, I. Yalcin, S. Sahin, A. U. Uslu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Familial Mediterranean fever (FMF) is an auto-inflammatory disorder. Long term complications of the disease include decreased quality of life. The measurement of quality of life in the patients with chronic disease has become an important research topic during the last years. <h3>Objectives</h3> In our study, we aimed to evaluate life quality of the FMF patients by SF–36, who are followed in Rheumatology Department of our University Medical Faculty Hospital, and examine its relationship with the disease parameters. <h3>Methods</h3> One hundred voluntary patients (69 female, 31 male) admitted to the rheumatology clinic at Cumhuriyet University Medical School were included in the study. The control group consisted of 100 healthy individuals. All subjects in the study were asked to complete SF–36 questionnaire. Age of onset of FMF, age at diagnosis, age at the beginning of colchicine therapy, number of attacks per month, family history of FMF and dialysis were inquired of patients with FMF. The patients were categorized as compliant or non-compliant based on their colchicine use. The response to colchicine was classified as complete response, partial response or non-response depending on the time between attacks. Disease severity was determined using the FMF severity score. <h3>Results</h3> The mean age of the patient group was 31±12 and that of the control group was 29 ±9. Sixty-nine patients (69%) were female, and 31 patients were male (31%) in both groups. No significant difference in sociodemographic variables were found between two groups (p&gt;0.05). The mean scores of the physical function, physical role function, emotional role function, mental health, and general health parameters of the patients were statistically significantly lower than those of healthy volunteers (p&lt;0.05). The difference in social function and physical fitness between two groups was found to be insignificant (p&gt;0.05). Comparison of quality of life scores of each grup were presented in Table 1. <h3>Conclusions</h3> We have shown that FMF had a negative impact on SF-36. In conclusion, FMF reduces quality of life both in physical and mental dimensions. This should be taken into account when planning treatment. To improve the health-related quality of life of patients with FMF, psychosocial approaches should accompany medical treatment. <h3>Disclosure of Interest</h3> None Declared
Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma
Authors: Brian A. Walker, Eileen M. Boyle, Christopher P. Wardell, Alex Murison, Dil B. Begum, Nasrin M. Dahir, Paula Z. Proszek, David C. Johnson, Martin F. Kaiser, Lorenzo Melchor, Lauren I. Aronson, Matthew Scales, Charlotte Pawlyn, Fabio Mirabella, John R. Jones, Annamaria Brioli, Aneta Mikulasova, David A. Cairns, Walter M. Gregory, Ana Quartilho, Mark T. Drayson, Nigel Russell, Gordon Cook, Graham H. Jackson, Xavier Leleu, Faith E. Davies, Gareth J. Morgan
Journal: Journal of Clinical Oncology (2015)

At the molecular level, myeloma is characterized by copy number abnormalities and recurrent translocations into the immunoglobulin heavy chain locus. Novel methods, such as massively parallel sequencing, have begun to describe the pattern of tumor-acquired mutations, but their clinical relevance has yet to be established.We performed whole-exome sequencing for 463 patients who presented with myeloma and were enrolled onto the National Cancer Research Institute Myeloma XI trial, for whom complete molecular cytogenetic and clinical outcome data were available.We identified 15 significantly mutated genes: IRF4, KRAS, NRAS, MAX, HIST1H1E, RB1, EGR1, TP53, TRAF3, FAM46C, DIS3, BRAF, LTB, CYLD, and FGFR3. The mutational spectrum is dominated by mutations in the RAS (43%) and nuclear factor-κB (17%) pathways, but although they are prognostically neutral, they could be targeted therapeutically. Mutations in CCND1 and DNA repair pathway alterations (TP53, ATM, ATR, and ZNFHX4 mutations) are associated with a negative impact on survival. In contrast, those in IRF4 and EGR1 are associated with a favorable overall survival. We combined these novel mutation risk factors with the recurrent molecular adverse features and international staging system to generate an international staging system mutation score that can identify a high-risk population of patients who experience relapse and die prematurely.We have refined our understanding of genetic events in myeloma and identified clinically relevant mutations that may be used to better stratify patients at presentation.
A strategy to reduce illicit drug use is effective in elite Australian football
Authors: Peter R Harcourt, Harry Unglik, Jill L Cook
Journal: British Journal of Sports Medicine (2012)

The World Anti-Doping Agency (WADA) prescribes that drug testing is conducted in sports competitions to detect drug use in athletes. This testing includes performance-enhancing drugs as well as illicit substances such as marijuana, amphetamines and cocaine. Illicit drugs are tested for on match days but not on non-match days. Some athletes are known to use illicit substances for recreational purposes, away from competition times and this poses a serious health and welfare issue not addressed by the usual sport drug testing regimes. This paper reports the results of the first 7 years of an illicit drug-testing programme that included non-match day testing in the elite Australian Football competition, the Australian Football League (AFL).Players in the AFL were tested for illicit drugs both in-competition and out-of-competition. Players were selected for illicit substance tests either randomly or targeted based on previous test history or time since previous test. The number of tests conducted was increased each year from 2005 to 2011 and testing was focused on high-risk times during non-competition periods.There were no positive match day tests. There was a significant reduction in positive tests (19-6) for illicit drugs during non-competition periods over the 7 years (p<0.0001). The reduction in positive tests may be related to player education, the greater number of tests conducted and the harm minimisation approach of the illicit drug policy.An illicit drugs programme using a harm minimisation strategy can work effectively alongside a sport's WADA compliant Anti-Doping Code.
Human and murine pituitary expression of leukemia inhibitory factor. Novel intrapituitary regulation of adrenocorticotropin hormone synthesis and secretion.
Authors: S Akita, J Webster, S G Ren, H Takino, J Said, O Zand, S Melmed
Journal: Journal of Clinical Investigation (1995)

Leukemia inhibitory factor (LIF) gene expression was detected in human fetal pituitary tissue by expression of LIF mRNA transcripts, protein immunocytochemistry, and immunoelectron microscopy. Fetal LIF immunoreactivity colocalized with 30% of ACTH-expressing cells, approximately 20% of somatotrophs, and approximately 15% of non-hormone-expressing cells. LIF was also strongly expressed in normal adult pituitary and in four growth hormone-producing and two ACTH-producing adenomas, but not in eight nonfunctioning pituitary tumors. Culture of fetal cells expressing surface LIF-binding sites demonstrated predominance of in vitro ACTH secretion as compared with other pituitary hormones. In AtT-20 murine cells, LIF (ED50 10 pM) stimulated basal proopiomelanocortin mRNA levels by 40% and corticotropin-releasing hormone-induced ACTH secretion (two- to threefold), as did oncostatin M (ED50 30 pM), a related peptide. ACTH responses were not further enhanced by both cytokines together, which is consistent with their shared receptor. Anti-LIF antiserum neutralized basal and LIF-induced ACTH secretion, suggesting autocrine regulation of ACTH by LIF. The results show that human pituitary cells express the LIF gene and LIF-binding sites, predominantly in corticotrophs. Pituitary LIF expression and LIF regulation of proopiomelanocortin and ACTH reflect an intrapituitary role for LIF in modulating early embryonic determination of specific human pituitary cells and as a paracrine or autocrine regulator of mature ACTH.
Problem of pressure on emergency services won't be solved overnight, government warns
Authors: A. O'Dowd
Journal: BMJ (2013)

Growing pressure on accident and emergency departments in hospitals in England could last for the foreseeable future, government officials have admitted to MPs, and there are no overnight solutions.

Health officials and the health minister Earl Howe appeared before the parliamentary health select committee on 25 June as part of its inquiry into emergency services and emergency care.

A review of urgent and emergency care review was announced in January,1 led by Bruce Keogh, medical director of NHS England, and an evidence base for that review was published last week.

MPs asked about the ongoing review of emergency services and whether naming a broad range of 12 priorities for commissioners in …
Increases in CSF levels of interleukin-2 in schizophrenia: effects of recurrence of psychosis and medication status
Authors: C G McAllister, D P van Kammen, T J Rehn, A L Miller, J Gurklis, M E Kelley, J Yao, J L Peters
Journal: American Journal of Psychiatry (1995)

Interleukin-2, traditionally viewed as solely involved in immunological events, has recently been shown to exert profound effects on the development and regulation of the central nervous system. This study examined the relationships between interleukin-2 in the CSF and plasma of schizophrenic patients and clinical measures, including relapse and medication status. Plasma and CSF interleukin-1 alpha levels were also measured to ascertain the specificity of changes in cytokine levels.Seventy-nine physically healthy male patients with schizophrenia (DSM-III-R) received diagnostic evaluation and behavioral ratings. Haloperidol treatment was withdrawn for up to 6 weeks and patients were evaluated for symptom recurrence. CSF and plasma were obtained by established procedures before haloperidol withdrawal (N = 79) and after (N = 64).CSF levels of interleukin-1 alpha decreased significantly after haloperidol withdrawal but showed no relation to clinical status. In contrast, levels of CSF interleukin-2 were associated with recurrence of psychotic symptoms. Relapse-prone patients, examined both while medicated and after drug withdrawal, had significantly higher levels of CSF interleukin-2 than patients who did not relapse. CSF interleukin-2 level during haloperidol treatment was a significant predictor of worsening in psychosis.Levels of interleukin-2, a molecule that plays both neurodevelopmental and neuroregulatory roles, may have a role in relapse in schizophrenia. Levels of CSF interleukin-2 appear to be affected by relapse mechanisms, while peripheral blood levels are not. These changes are specific to interleukin-2, since levels of interleukin-1 alpha were affected by medication withdrawal but not by change in clinical state.
Reversion of CTL escape–variant immunodeficiency viruses in vivo
Authors: Thomas C Friedrich, Elizabeth J Dodds, Levi J Yant, Lara Vojnov, Richard Rudersdorf, Candice Cullen, David T Evans, Ronald C Desrosiers, Bianca R Mothé, John Sidney, Alessandro Sette, Kevin Kunstman, Steven Wolinsky, Michael Piatak, Jeffrey Lifson, Austin L Hughes, Nancy Wilson, David H O'Connor, David I Watkins
Journal: Nature Medicine (2004)
Ulcerative colitis complicated by Budd-Chiari syndrome.
Authors: I M Chesner, S Muller, J Newman
Journal: Gut (1986)

We present two cases of ulcerative colitis associated with a chronic pattern of hepatic vein thrombosis (Budd-Chiari syndrome). Progression of the hepatic disorder appeared to be unrelated to the activity of the colitis. Liver function tests were normal until a late stage in the disease except for a high serum alkaline phosphate and a low serum albumin. This combination of abnormalities together with ascites merit further investigation and should raise the suspicion of hepatic vein thrombosis complicating ulcerative colitis.
Effects of the New Dual PPARα/δ Agonist GFT505 on Lipid and Glucose Homeostasis in Abdominally Obese Patients With Combined Dyslipidemia or Impaired Glucose Metabolism
Authors: Bertrand Cariou, Yassine Zaïr, Bart Staels, Eric Bruckert
Journal: Diabetes Care (2011)

OBJECTIVE We evaluated the metabolic effects and tolerability of GFT505, a novel dual peroxisome proliferator–activated receptor α/δ agonist, in abdominally obese patients with either combined dyslipidemia or prediabetes. RESEARCH DESIGN AND METHODS The S1 study was conducted in 94 patients with combined dyslipidemia while the S2 study was conducted in 47 patients with prediabetes. Participants were randomly assigned in a double-blind manner to GFT505 at 80 mg/day or placebo for 28 (S1) or 35 (S2) days. Primary efficacy end points were changes from baseline at week 4 in both fasting plasma triglycerides and HDL cholesterol in the S1 group and 2-h glucose upon oral glucose tolerance test in the S2 group. RESULTS In comparison with placebo, GFT505 significantly reduced fasting plasma triglycerides (S1: least squares means −16.7% [95% one-sided CI −∞ to −5.3], P = 0.005; S2: −24.8% [−∞ to −10.5], P = 0.0003) and increased HDL cholesterol (S1: 7.8% [3.0 to ∞], P = 0.004; S2: 9.3% [1.7 to ∞], P = 0.009) in both studies, whereas LDL cholesterol only decreased in S2 (−11.0% [ −∞ to −3.5], P = 0.002). In S2, GFT505 did not reduce 2-h glucose (−0.52 mmol/L [−∞ to 0.61], P = 0.18) but led to a significant decrease of homeostasis model assessment of insulin resistance (−31.4% [−∞ to 12.5], P = 0.001), fasting plasma glucose (−0.37 mmol/L [−∞ to −0.10], P = 0.01) and fructosamine (−3.6% [−∞ to −0.20], P = 0.02). GFT505 also reduced γ glutamyl transferase levels in both studies (S1: −19.9% [−∞ to −12.8], P &amp;lt; 0.0001; S2: −15.1% [−∞ to −1.1], P = 0.004). No specific adverse safety signals were reported during the studies. CONCLUSIONS GFT505 may be considered a new drug candidate for the treatment of lipid and glucose disorders associated with the metabolic syndrome.
Scores for Post–Myocardial Infarction Risk Stratification in the Community
Authors: Mandeep Singh, Guy S. Reeder, Steven J. Jacobsen, Susan Weston, Jill Killian, Véronique L. Roger
Journal: Circulation (2002)

Several scores, most of which were derived from clinical trials, have been proposed for stratifying risk after myocardial infarctions (MIs). Little is known about their generalizability to the community, their respective advantages, and whether the ejection fraction (EF) adds prognostic information to the scores. The purpose of this study is to evaluate the Thrombolysis in Myocardial Infarction (TIMI) and Predicting Risk of Death in Cardiac Disease Tool (PREDICT) scores in a geographically defined MI cohort and determine the incremental value of EF for risk stratification.MIs occurring in Olmsted County were validated with the use of standardized criteria and stratified with the ECG into ST-segment elevation (STEMI) and non-ST-segment elevation (NSTEMI) MI. Logistic regression examined the discriminant accuracy of the TIMI and PREDICT scores to predict death and recurrent MI and assessed the incremental value of the EF. After 6.3+/-4.7 years, survival was similar for the 562 STEMIs and 717 NSTEMIs. The discriminant accuracy of the TIMI score was good in STEMI but only fair in NSTEMI. Across time and end points, irrespective of reperfusion therapy, the discriminant accuracy of the PREDICT score was consistently superior to that of the TIMI scores, largely because PREDICT includes comorbidity; EF provided incremental information over that provided by the scores and comorbidity.In the community, comorbidity and EF convey important prognostic information and should be included in approaches for stratifying risk after MI.
Human CD4+ T Lymphocytes Recognize a Vascular Endothelial Growth Factor Receptor-2–Derived Epitope in Association with HLA-DR
Authors: Yuansheng Sun, Mingxia Song, Elke Jäger, Christina Schwer, Stefan Stevanovic, Sven Flindt, Julia Karbach, Xuan D. Nguyen, Dirk Schadendorf, Klaus Cichutek
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Given the multiple escape mechanisms of tumor cells, immunotherapy targeting tumor-dependent stroma may be an effective cancer treatment strategy. Animal models indicate that inducing immunity to tumor endothelia engenders potent antitumor effects without significant pathology. Recently, the first human tumor endothelial antigen vascular endothelial growth factor receptor-2 (VEGFR-2) recognized by HLA class I–restricted CD8+ T cells has been characterized. In this study, we sought to investigate specific recognition of this molecule by human CD4+ T cells. Experimental Design: To identify HLA-DR–restricted antigenic peptides on VEGFR-2 recognized by CD4+ T cells of healthy donors and cancer patients. Results: Nine candidate VEGFR-2 peptides with high binding probability to six common HLA-DRB1 alleles were synthesized using the SYFPEITHI algorithm. One 15-mer peptide (EKRFVPDGNRISWDS), mapping to the 167-181 region of VEGFR-2, stimulated CD4+ T cells in association with several HLA-DR alleles, including DR4 and DR7. Importantly, the epitope could be naturally processed and presented both by HLA-DR–matched antigen-expressing proliferating endothelial cells and by dendritic cells loaded with the native antigen. Furthermore, circulating VEGFR-2–specific CD4+ T cells were detected in 4 of 10 healthy donors and 12 of 40 cancer patients even after single-round peptide stimulation in short-term culture. Patient's T cells could recognize antigen-expressing proliferating endothelial cells in a HLA-DR–restricted fashion. Conclusion: These findings indicate an important role for the 167-181 region of VEGFR-2 in the stimulation of CD4+ T cell responses to VEGFR-2 protein, and may be instrumental both for the development and monitoring of upcoming antitumor vessel vaccines against different cancers based on VEGFR-2 immunogens.
Bionanotechnology based on silica nanoparticles
Authors: Weihong Tan, Kemin Wang, Xiaoxiao He, Xiaojun Julia Zhao, Timothy Drake, Lin Wang, Rahul P. Bagwe
Journal: Medicinal Research Reviews (2004)

We have developed uniform core/shell nanoparticles, consisting of a silica layer coating and pigments or magnetite core, using a water-in-oil microemulsion method. The nanoparticles are highly luminescent and photostable with the size ranging from 5 nm to 400 nm. Bioconjugation of these silica nanoparticles adds unique biofunctions with various molecules such as enzymes, antibodies, and DNA molecules. Significant advantages have been shown in using bioconjugated nanoparticles for biosensing and bioimaging, such as cell staining, DNA detection and separation, rapid single bacterium detection, and biotechnological application in DNA protection.