tbuckley/cabot-search huggingface dataset:
Metallothionien 3 expression is frequently down-regulated in oesophageal squamous cell carcinoma by DNA methylation
Authors: Eric Smith, Paul A Drew, Zi-Qing Tian, Neville J De Young, Jun-Feng Liu, George C Mayne, Andrew R Ruszkiewicz, David I Watson, Glyn G Jamieson
Journal: Molecular Cancer (2005)

Abstract Background Metallothionein 3 (MT3) inhibits growth in a variety of cell types. We measured MT3 gene expression by RT-PCR, and DNA methylation in the MT3 promoter by combined bisulphite restriction analysis, in four oesophageal cancer cell lines and the resected oesophagus from 64 patients with oesophageal squamous cell carcinoma (SCC). Results MT3 expression was not detected in one of the four oesophageal cell lines. The MT3 promoter was methylated in all of the oesophageal cell lines, but the degree of methylation was greater in the non-expressing cell line. After treatment with 5-aza-2'-deoxycytidine there was a reduction in the degree of methylation, and an increase in MT3 expression, in each of the cell lines (p &lt; 0.01). Methylation was detected in 52% (33 of 64) of primary SCC and 3% (2 of 62) of histologically normal resection margins. MT3 expression was measured in 29 tumours, 17 of which had methylation of MT3 . The expression of MT3 was significantly less in the methylated tumours compared to either the unmethylated tumours (p = 0.03), or the matched margin (p = 0.0005). There was not a significant difference in MT3 expression between the tumour and the margin from patients with unmethylated tumour. No correlations were observed between methylation of MT3 and survival time, patient age, gender, smoking or drinking history, tumour stage, volume, or lymph node involvement. Conclusion We conclude that MT3 ex pression is frequently down-regulated in oesophageal SCC, by DNA methylation, but that this is not a prognostic indicator.
Tolerance of a cow's milk-based hydrolyzed formula in patients with eosinophilic esophagitis triggered by milk
Authors: A. J. Lucendo, Á. Arias, J. González-Cervera, T. Mota-Huertas, J. L. Yagüe-Compadre
Journal: Allergy (2013)

Cow's milk protein, a major food trigger for EoE in both children and adults, should be continuously avoided once identified as such. This study evaluates tolerance of a cow's milk-based extensively hydrolyzed formula (eHF) with regard to disease remission maintenance in adult patients with milk-triggered EoE.Seventeen adult patients in whom cow's milk was consecutively demonstrated to trigger EoE after an empiric six-food elimination diet-based study protocol and who subsequently maintained disease remission were prospectively recruited. They were given 400 ml of a cow's milk-based eHF daily for 8 weeks. Intraepithelial peak eosinophil and blood eosinophil counts, esophageal-related symptoms, serum total and specific IgE to major milk proteins, and eosinophil cationic protein were monitored before and after eHF intake.Thirteen male and four female patients aged 17-56 completed the study protocol. 15 patients (88.24%) achieved and maintained EoE remission, while an infiltration of ≥15 eosinophils/hpf reappeared in the remaining two patients. No differences in age, gender, symptoms, and endoscopic appearance at baseline conditions or personal/family allergic background were observed between those patients who tolerated the eHF and those who did not. Symptom scores did not significantly change after eHF intake and were significantly lower than those documented at baseline conditions or after cow's milk challenge. No differences were documented in blood eosinophil counts or serum markers after eHF intake.Most adult patients with EoE triggered by cow's milk tolerate a cow's milk-based eHF, thus providing them with a safe, economical alternative to cow's milk.
Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study
Authors: R Schellenberg
Journal: BMJ (2001)

Objectives: To compare the efficacy and tolerability of agnus castus fruit ( Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome. Design: Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles. Setting: General medicine community clinics. Participants: 178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days. Interventions: Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles. Main outcome measures: Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms). Results: Improvement in the main variable was greater in the active group compared with placebo group (P<0.001). Analysis of the secondary variables showed significant (P<0.001) superiority of active treatment in each of the three global impression items. Responder rates were 52% and 24% for active and placebo, respectively. Seven women reported mild adverse events (four active; three placebo), none of which caused discontinuation of treatment. Conclusions: Dry extract of agnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome.
Failure of ursodeoxycholic acid to prevent a cholestatic episode in a patient with benign recurrent intrahepatic cholestasis: A study of bile acid metabolism
Authors: Andrea Crosigani, Mauro Podda, Emanuela Bertolini, Pier Maria Battezzati, Massimo Zuin, Kenneth D. R. Setchell
Journal: Hepatology (1991)

Ursodeoxycholic acid was administered to a patient with benign recurrent intrahepatic cholestasis to prevent cholestatic episodes. A detailed study of bile acid metabolism in this patient was carried out in the anicteric and icteric phases before and after ursodeoxycholic acid (750 mg/day) administration. Urinary, biliary and serum bile acids were measured by gas chromatography-mass spectrometry and by high-performance liquid chromatography techniques. During the anicteric phase the daily urinary excretion and serum concentrations of bile acids were within normal ranges, indicating normal hepatic uptake and secretion of bile acids during the cholestasis-free period. Only slight qualitative differences from normal individuals were observed; the relative proportions of deoxycholic acid in the bile and serum were higher, and 12-oxo-lithocholic acid was the predominant urinary bile acid. During the icteric phase a marked increase in the urinary excretion of primary bile acids and C-1, C-2, C-4 and C-6 hydroxylated metabolites was found. Serum bile acid concentrations increased before the rise in bilirubin, suggesting an acute disturbance in bile acid transport at the onset of the cholestatic attack. After ursodeoxycholic acid administration in the anicteric phase, bile became enriched with the exogenous bile acid, but little qualitative change was found in the other metabolites present in the urine, serum or bile during the anicteric or icteric phases. Prolonged administration of ursodeoxycholic acid failed to prevent recurrence of a cholestatic episode, suggesting that in benign recurrent intrahepatic cholestasis, oral ursodeoxycholic acid may be of little benefit in the treatment or prevention of cholestasis despite marked enrichment of the bile acid pool with this hydrophilic bile acid.
Impaired homocysteine transsulfuration is an indicator of alcoholic liver disease
Authors: Valentina Medici, Janet M. Peerson, Sally P. Stabler, Samuel W. French, Jesse F. Gregory, Maria Catrina Virata, Antony Albanese, Christopher L. Bowlus, Sridevi Devaraj, Edward A. Panacek, Nazir Rahim, John R. Richards, Lorenzo Rossaro, Charles H. Halsted
Journal: Journal of Hepatology (2010)
Impact of Disease Risk on Efficacy of Matched Related Bone Marrow Transplantation for Pediatric Acute Myeloid Leukemia: The Children's Oncology Group
Authors: John T. Horan, Todd A. Alonzo, Gary H. Lyman, Robert B. Gerbing, Beverly J. Lange, Yaddanapudi Ravindranath, David Becton, Franklin O. Smith, William G. Woods
Journal: Journal of Clinical Oncology (2008)

There is considerable variation in the use of HLA-matched related bone marrow transplantation (BMT) for the treatment of pediatric patients with newly diagnosed acute myeloid leukemia (AML). Some oncologists have argued that BMT should be offered to most patients in first complete remission (CR). Others have maintained that transplantation in first remission should be reserved for patients with high-risk disease. We performed this study to determine how disease risk influences the efficacy of BMT.We combined data from four cooperative group clinical trials: Pediatric Oncology Group 8821, Children's Cancer Group (CCG) 2891, CCG 2961, and Medical Research Council 10. Using cytogenetics and the percentage of marrow blasts after the first course of chemotherapy, patients were stratified into favorable, intermediate, and poor-risk disease groups. Patients who could not be risk classified were analyzed separately. Outcomes for patients assigned to BMT and for patients assigned to chemotherapy alone were compared.The data set included 1,373 pediatric patients with AML in first CR. In the intermediate-risk group, the estimated disease-free survival at 8 years for patients who did not undergo transplantation was 39% +/- 5% (2 SE), whereas it was 58% +/- 7% for BMT patients. The estimated overall survival for patients who did not undergo transplantation was 51% +/- 5%, whereas it was 62% +/- 7% for BMT patients. Both differences were significant (P < .01). There were no significant differences for survival in the other two risk groups or in the non-risk-stratified patients.Our study indicates that HLA-matched related BMT is an effective treatment for pediatric patients with intermediate-risk AML in first CR.
FOXP3: Of Mice and Men
Authors: Steven F. Ziegler
Journal: Annual Review of Immunology (2005)

The immune system has evolved mechanisms to recognize and eliminate threats, as well as to protect against self-destruction. Tolerance to self-antigens is generated through two fundamental mechanisms: (a) elimination of self-reactive cells in the thymus during selection and (b) generation of a variety of peripheral regulatory cells to control self-reactive cells that escape the thymus. It is becoming increasing apparent that a population of thymically derived CD4 + regulatory T cells, exemplified by the expression of the IL-2Rα chain, is essential for the maintenance of peripheral tolerance. Recent work has shown that the forkhead family transcription factor Foxp3 is critically important for the development and function of the regulatory T cells. Lack of Foxp3 leads to development of fatal autoimmune lymphoproliferative disease; furthermore, ectopic Foxp3 expression can phenotypically convert effector T cells to regulatory T cells. This review focuses on Foxp3 expression and function and highlights differences between humans and mice regarding Foxp3 regulation.
The Effect of Tobacco Control Measures during a Period of Rising Cardiovascular Disease Risk in India: A Mathematical Model of Myocardial Infarction and Stroke
Authors: Sanjay Basu, Stanton Glantz, Asaf Bitton, Christopher Millett
Journal: PLoS Medicine (2013)

In this paper from Basu and colleagues, a simulation of tobacco control and pharmacological interventions to prevent cardiovascular disease mortality in India predicted that Smokefree laws and increased tobacco taxation are likely to be the most effective measures to avert future cardiovascular deaths in India. Please see later in the article for the Editors' Summary
A genome wide analysis of the response to uncapped telomeres in budding yeast reveals a novel role for the NAD+ biosynthetic gene BNA2 in chromosome end protection
Authors: Amanda Greenall, Guiyuan Lei, Daniel C Swan, Katherine James, Liming Wang, Heiko Peters, Anil Wipat, Darren J Wilkinson, David Lydall
Journal: Genome biology (2008)

Telomeres prevent the ends of eukaryotic chromosomes from being recognized as damaged DNA and protect against cancer and ageing. When telomere structure is perturbed, a co-ordinated series of events promote arrest of the cell cycle so that cells carrying damaged telomeres do not divide. In order to better understand the eukaryotic response to telomere damage, budding yeast strains harboring a temperature sensitive allele of an essential telomere capping gene (cdc13-1) were subjected to a transcriptomic study. The genome-wide response to uncapped telomeres in yeast cdc13-1 strains, which have telomere capping defects at temperatures above approximately 27°C, was determined. Telomere uncapping in cdc13-1 strains is associated with the differential expression of over 600 transcripts. Transcripts affecting responses to DNA damage and diverse environmental stresses were statistically over-represented. BNA2, required for the biosynthesis of NAD+, is highly and significantly up-regulated upon telomere uncapping in cdc13-1 strains. We find that deletion of BNA2 and NPT1, which is also involved in NAD+ synthesis, suppresses the temperature sensitivity of cdc13-1 strains, indicating that NAD+ metabolism may be linked to telomere end protection. Our data support the hypothesis that the response to telomere uncapping is related to, but distinct from, the response to non-telomeric double-strand breaks. The induction of environmental stress responses may be a conserved feature of the eukaryotic response to telomere damage. BNA2, which is involved in NAD+ synthesis, plays previously unidentified roles in the cellular response to telomere uncapping.
Inflammatory Markers and Risk of Type 2 Diabetes
Authors: Xia Wang, Wei Bao, Jun Liu, Ying-Ying OuYang, Di Wang, Shuang Rong, Xiao Xiao, Zhi-Lei Shan, Yan Zhang, Ping Yao, Lie-Gang Liu
Journal: Diabetes Care (2012)

OBJECTIVE There has been growing evidence that inflammatory markers play a role in the development of type 2 diabetes. We aimed to systematically review prospective studies on the associations of elevated levels of interleukin-6 (IL-6) and C-reactive protein (CRP) with increased risk of type 2 diabetes by conducting a meta-analysis. RESEARCH DESIGN AND METHODS A systematic search of the PubMed, EMBASE, ISI Web of Knowledge, and Cochrane Library databases up until 10 February 2012 was conducted to retrieve prospective studies matched to search terms. We used generalized least-squares trend estimation to assess dose-response relationships. The summary risk estimates were pooled using either fixed-effects or random-effects models to incorporate between-study variation. RESULTS The meta-analysis, including 10 prospective studies, with a total of 19,709 participants and 4,480 cases, detected a significant dose-response association of IL-6 levels with type 2 diabetes risk (relative risk [RR] 1.31 [95% CI 1.17–1.46]). For CRP, the meta-analysis involving 22 cohorts, with a total of 40,735 participants and 5,753 cases, showed that elevated CRP levels were significantly associated with increased risk of type 2 diabetes (1.26 [1.16–1.37]), with the absence of publication bias. Sensitivity and subgroup analyses further supported the associations. CONCLUSIONS This meta-analysis provides further evidence that elevated levels of IL-6 and CRP are significantly associated with increased risk of type 2 diabetes.
Risk of second primary malignancies in patients with cutaneous melanoma
Authors: M-H. Schmid-Wendtner, J. Baumert, C-M. Wendtner, G. Plewig, M. Volkenandt
Journal: British Journal of Dermatology (2001)

Journal Article Risk of second primary malignancies in patients with cutaneous melanoma Get access M‐H. Schmid‐Wendtner, M‐H. Schmid‐Wendtner Monika‐H.Schmid‐Wendtner.E‐mail: M.Schmid‐Wendtner@LRZ.uni‐muenchen.de Search for other works by this author on: Oxford Academic Google Scholar J. Baumert, J. Baumert Search for other works by this author on: Oxford Academic Google Scholar C‐M. Wendtner, C‐M. Wendtner Department of Hematology and Oncology, Klinikum Großhadern, Ludwig‐Maximilians‐University, 81377 Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar G. Plewig, G. Plewig Search for other works by this author on: Oxford Academic Google Scholar M. Volkenandt M. Volkenandt Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 145, Issue 6, 1 December 2001, Pages 981–985, https://doi.org/10.1046/j.1365-2133.2001.04507.x Published: 01 December 2001
Synonymous Genetic Variation in Natural Isolates of<i>Escherichia coli</i>Does Not Predict Where Synonymous Substitutions Occur in a Long-Term Experiment
Authors: Rohan Maddamsetti, Philip J. Hatcher, Stéphane Cruveiller, Claudine Médigue, Jeffrey E. Barrick, Richard E. Lenski
Journal: Molecular Biology and Evolution (2015)

Synonymous genetic differences vary by more than 20-fold among genes in natural isolates of Escherichia coli. One hypothesis to explain this heterogeneity is that genes with high levels of synonymous variation mutate at higher rates than genes with low synonymous variation. If so, then one would expect to observe similar mutational patterns in evolution experiments. In fact, however, the pattern of synonymous substitutions in a long-term evolution experiment with E. coli does not support this hypothesis. In particular, the extent of synonymous variation across genes in that experiment does not reflect the variation observed in natural isolates of E. coli. Instead, gene length alone predicts with high accuracy the prevalence of synonymous changes in the experimental populations. We hypothesize that patterns of synonymous variation in natural E. coli populations are instead caused by differences across genomic regions in their effective population size that, in turn, reflect different histories of recombination, horizontal gene transfer, selection, and population structure.
Higher Intron Loss Rate in Arabidopsis thaliana Than A. lyrata Is Consistent with Stronger Selection for a Smaller Genome
Authors: J. A. Fawcett, P. Rouze, Y. Van de Peer
Journal: Molecular Biology and Evolution (2011)

The number of introns varies considerably among different organisms. This can be explained by the differences in the rates of intron gain and loss. Two factors that are likely to influence these rates are selection for or against introns and the mutation rate that generates the novel intron or the intronless copy. Although it has been speculated that stronger selection for a compact genome might result in a higher rate of intron loss and a lower rate of intron gain, clear evidence is lacking, and the role of selection in determining these rates has not been established. Here, we studied the gain and loss of introns in the two closely related species Arabidopsis thaliana and A. lyrata as it was recently shown that A. thaliana has been undergoing a faster genome reduction driven by selection. We found that A. thaliana has lost six times more introns than A. lyrata since the divergence of the two species but gained very few introns. We suggest that stronger selection for genome reduction probably resulted in the much higher intron loss rate in A. thaliana, although further analysis is required as we could not find evidence that the loss rate increased in A. thaliana as opposed to having decreased in A. lyrata compared with the rate in the common ancestor. We also examined the pattern of the intron gains and losses to better understand the mechanisms by which they occur. Microsimilarity was detected between the splice sites of several gained and lost introns, suggesting that nonhomologous end joining repair of double-strand breaks might be a common pathway not only for intron gain but also for intron loss.
P272 A 7 year retrospective evaluation of initiation of long term non-invasive ventilatory support for motor neurone disease
Authors: J. Palmer, P. Hughes
Journal: Thorax (2011)

In 2010 NICE (1) published it9s guideline for the use of non-invasive ventilation in the management of motor neurone disease (MND). We have offered long-term non-invasive ventilation (NIV) in this patient group for7 years. We have evaluated concordance data for all patients set-up during this time. <h3>Methodology</h3> Data were obtained by retrospective case-note review of all patients set-up on NIV for MND between April 2004 and March 2011inclusive. <h3>Results</h3> 42 patients were set-up over 7 years. Mean length of time from diagnosis to ventilation was 13.9 months, with three patients being set-up on diagnosis and a further three before diagnosis. 69% (n=29) were set-up at home, the remainder in hospital. 71% (n=30) of those set up were eventually concordant, 19% (n=8) did not tolerate NIV, while 10% (n=4) died during initiation. Those set-up in hospital had a tendency to be more concordant with ventilation than those set-up at home (76% vs 69%). This group also became concordant more rapidly (4.4 days vs 14.2 days). Those with both symptomatic and physiological indications for ventilation appeared to tolerate it extremely well with 84% (n=24) becoming concordant. There was a failure rate of 75% of those with physiological indications only. Of those with symptoms only and no apparent abnormal physiological markers 80% (n=4) complied with treatment. Symptomatically daytime somnolence was the most commonly reported symptom, with 81% (n=34) of patients being sleepy by day. Nocturia was the least commonly reported at 11%. In terms of mortality, mean survival from initiation to death was 10.2 months (range 0.67–84). In total three patients progressed from NIV to tracheostomy ventilation, one of these survived a further 5 years. <h3>Conclusion</h3> Those with MND have a tendency to have better concordance with NIV if started in hospital rather than at home; concordance also appears to be more rapid in this group. As expected, given the nature of this treatment those without symptoms tend not to tolerate NIV.
TGF-β is a critical mediator of acute lung injury
Authors: Jean-Francois Pittet, Mark J.D. Griffiths, Tom Geiser, Naftali Kaminski, Stephen L. Dalton, Xiaozhu Huang, Lou Anne S. Brown, Phillip J. Gotwals, Victor E. Koteliansky, Michael A. Matthay, Dean Sheppard
Journal: Journal of Clinical Investigation (2001)

We have shown that the integrin αvβ6 activates latent TGF-β in the lungs and skin. We show here that mice lacking this integrin are completely protected from pulmonary edema in a model of bleomycin-induced acute lung injury (ALI). Pharmacologic inhibition of TGF-β also protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin. TGF-β directly increased alveolar epithelial permeability in vitro by a mechanism that involved depletion of intracellular glutathione. These data suggest that integrin-mediated local activation of TGF-β is critical to the development of pulmonary edema in ALI and that blocking TGF-β or its activation could be effective treatments for this currently untreatable disorder.