tbuckley/cabot-search huggingface dataset:
Deletion of the<i>PER3</i>Gene on Chromosome 1p36 in Recurrent ER-Positive Breast Cancer
Authors: Joan Climent, Jesus Perez-Losada, David A. Quigley, Il-Jin Kim, Reyno Delrosario, Kuang-Yu Jen, Ana Bosch, Ana Lluch, Jian-Hua Mao, Allan Balmain
Journal: Journal of Clinical Oncology (2010)

Purpose To investigate the role of the PER3 circadian rhythm gene, located within the commonly deleted region of chromosome 1p36, in human breast cancer development. Patients and Methods The frequency of genetic alterations at 1p36 and PER3 gene copy number status were analyzed in 180 lymph node–negative breast cancers from patients who had received treatment with chemotherapy and/or tamoxifen. The expression levels of PER3 were also analyzed using published microarray profiles from &gt; 400 breast cancer samples. Finally, the effect of loss of Per3 on tumor susceptibility was tested using two mouse models of breast cancer. Results Deletion of PER3 is directly related to tumor recurrence in patients with estrogen receptor (ER) – positive breast cancers treated with tamoxifen. Low expression of PER3 mRNA is associated with poor prognosis, particularly in a subset of tumors that are ER positive, and either luminal A or ERBB2-positive tumors. Mice deficient in Per3 showed increased susceptibility to breast cancer induced by carcinogen treatment or by overexpression of Erbb2. Conclusion Disruption of PER3 function may serve as an indicator of probability of tumor recurrence in patients with ER-positive tumors. Further investigations of this pathway may reveal links between deregulation of sleep homeostasis and breast tumorigenesis.
Parental choice on normalising cosmetic genital surgery
Authors: Lih-Mei Liao, Dan Wood, Sarah M Creighton
Journal: BMJ (2015)

<b>Dr Jessica Eccles</b> trained in medicine at University of Cambridge and University of Oxford, completing a BA in The History and Philosophy of Science, sparking a keen interest in philosophy of mind and brain-body interactions. Since graduation from medical school has pursued a combined academic clinical path at Brighton and Sussex Medical School. As an MRC Clinical Research Training Fellow she recently completed her PhD in the relationship between joint hypermobility, autonomic dysfunction and psychiatric symptoms and is now an NIHR Clinical Lecturer. She is currently working on an Academy of Medical Sciences grant to explore neural connectivity in hypermobility using leading edge Human Connectome Project techniques and has recently been awarded a MQ Arthritis Research UK Fellows Award to conduct a randomised clinical trial of a new targeted treatment for anxiety in hypermobility. Dr Eccles has also been awarded a grant from Dysautonomia International and will be working with Profs Critchley, Cercignani, Rowe, Murphy and Drs Nagai, Asslanni, Iodice and Giovanni to explore multi-modal correlates of ‘brain fog’ in Postural Tachycardia Syndrome. Dr Eccles is working with Profs Davies, Harrison, Cercignani, Critchley and Dr Tarzi to explore brain- body interactions in Fibromyalgia and ME/CFS. This involves autonomics, inflammatory and cytokine markers, brain imaging and genomics. This work is funded by Versus Arthritis and Action for ME Alongside clinical academic colleagues at BSMS, Prof Harrison and Dr Colasanti. Joint hypermobility is a common, yet poorly recognised variant of connective tissue affecting up to 20% of the population. Hypermobility is a cardinal feature of Hyermobility Spectrum Disorder (HSD) and hypermobile Ehlers Danlos Syndrome (hEDS), inherited disorders of connective tissue. Individuals with joint hypermobility are over represented in panic, anxiety and neurodevelopmental populations and are prone to dysautonomia, typically postural tachycardia syndrome (PoTS), in which there is a phenomenological overlap with anxiety disorder. Interestingly differences in brain structure and function have been described in hypermobility in regions associated with emotional processing, including amygdala and insula. Individuals with joint hypermobility are more likely to experience severe chronic widespread pain, and many have co-morbid rheumatic conditions. A data-driven theoretical model linking joint hypermobility to psychiatric disorder is proposed, characterised by aberrant autonomic control and central representation, grounded in current theoretical models that seek to frame emotion as interoceptive inference, using leading-edge predictive coding approaches. Ultimately this approach has considerable relevance to personalised psychiatric medicine in this disorder and greater understanding of brain-body mechanisms underpinning neuropsychiatric states.
PMO-239 Inflammatory bowel disease and pregnancy: lack of knowledge is associated with negative patient views
Authors: C Selinger, J McLaughlin, J Eaden, R Leong, S Lal
Journal: Gut (2012)

<h3>Introduction</h3> Enabling women with inflammatory bowel diseases (IBD) to a have successful pregnancy requires complex decisions. This study aimed to assess patients9 views on IBD and pregnancy and to correlate them with knowledge. <h3>Methods</h3> Female IBD patients aged 18–45 years were recruited from Australian gastroenterology clinics and private offices. Data were collected on demographics, disease specifics and previous pregnancies. General attitudes were assessed on fertility, medication use, mode of delivery and pregnancy outcomes. Attitudes regarding their personal situation were assessed in participants who had not given birth since their diagnosis of IBD. Agreement was rated on 5 Point Likert scales and knowledge of pregnancy related issues in IBD was assessed by the recently validated Crohn9s and Colitis Pregnancy Knowledge Score “CCPKnow”. Statistical analysis was performed using Student t test and ANOVA. <h3>Results</h3> Of 145 women (median age 32 years, 70% married) 45% had Crohn9s disease, 45% ulcerative colitis and 10% IBD-unclassified. 49 women had successfully delivered children after their diagnosis of IBD. <i>General attitudes</i>: Only 51% agreed that IBD medication should be continued prior to conception. 68% agreed with the need for medical therapy for flares during pregnancy, but 24% felt it more important to tolerate symptoms rather than to have medicines. 36% of participants believed that any IBD medication is “bad” for unborn children. Patients believed that women with IBD are likely to have a vaginal delivery (87%) or a healthy baby (68%), but 37% expected a difficult pregnancy. 70% thought that women on IBD medication should not breastfeed. <i>Personal attitudes</i>: Of 96 nulliparous women after IBD diagnosis, 46% were worried about infertility, passing IBD to offspring (75%) and 30% considered not having children because of IBD. 90% worried about the effect of IBD on pregnancy and 91% about the effects of pregnancy on IBD. <i>Correlation of attitudes and knowledge</i>: General attitudes that “medication should be stopped prior to conception” (p&lt;0.001), “pregnant women should avoid all IBD drugs” (p&lt;0.001), and “put up with symptoms” (p&lt;0.001) were all associated with significantly lower knowledge. Personal attitudes were not associated with knowledge. <h3>Conclusion</h3> A significant minority of women felt that IBD medication is harmful to unborn children and women should put up with symptoms. Fear of infertility and concerns about inheritance may explain the extremely high rate of women considering not having children because of IBD. Views contrary to medical evidence were associated with significantly lower knowledge; education and personal counselling should be offered to young women with IBD, particularly those with a low CCPKnow score. <h3>Competing interests</h3> None declared.
STUDIES ON THE INHIBITION OF PROTEOLYTIC ENZYMES BY SERUM
Authors: N. Raphael Shulman
Journal: The Journal of Experimental Medicine (1952)

Increases in serum proteolytic inhibition with disease were found to be specific either for plasmin or for trypsin and chymotrypsin. In normal serum, the plasmin inhibitor could be differentiated from the trypsin and chymotrypsin inhibitor by various physical and chemical means. There was no apparent difference between the trypsin inhibitor and the chymotrypsin inhibitor in serum. No qualitative differences were found between the inhibitors of normal sera and the inhibitors of sera showing elevated inhibition.
CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies
Authors: S Ogino
Journal: Gut (2006)

The concept of CpG island methylator phenotype (CIMP) is not universally accepted. Even if specific clinicopathological features have been associated with CIMP, investigators often failed to demonstrate a bimodal distribution of the number of methylated markers, which would suggest CIMP as a distinct subtype of colorectal cancer. Previous studies primarily used methylation specific polymerase chain reaction which might detect biologically insignificant low levels of methylation.To demonstrate a distinct genetic profile of CIMP colorectal cancer using quantitative DNA methylation analysis that can distinguish high from low levels of DNA methylation.We developed quantitative real time polymerase chain reaction (MethyLight) assays and measured DNA methylation (percentage of methylated reference) of five carefully selected loci (promoters of CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 460 colorectal cancers from large prospective cohorts.There was a clear bimodal distribution of 80 microsatellite instability-high (MSI-H) tumours according to the number of methylated promoters, with no tumours showing 3/5 methylated loci. Thus we defined CIMP as having >or=4/5 methylated loci, and 17% (78) of the 460 tumours were classified as CIMP. CIMP was significantly associated with female sex, MSI, BRAF mutations, and wild-type KRAS. Both CIMP MSI-H tumours and CIMP microsatellite stable (MSS) tumours showed much higher frequencies of BRAF mutations (63% and 54%) than non-CIMP counterparts (non-CIMP MSI-H (0%, p<10(-5)) and non-CIMP MSS tumours (6.6%, p<10(-4)), respectively).CIMP is best characterised by quantitative DNA methylation analysis. CIMP is a distinct epigenotype of colorectal cancer and may be less frequent than previously reported.
POORLY CONTROLLED BLOOD PRESSURE IS INDEPENDENTLY ASSOCIATED WITH A 50% HIGHER RISK OF STROKE OR SYSTEMIC EMBOLISM IN PATIENTS WITH ATRIAL FIBRILLATION: RESULTS FROM THE ARISTOTLE TRIAL
Authors: Meena Rao, Sigrun Halvorsen, Daniel Wojdyla, John Alexander, Renato Lopes, Elaine Hylek, Michael Hanna, Maria Bahit, Raffaele De Caterina, Cetin Erol, Shinya Goto, Fernando Lanas, Basil Lewis, Steen Husted, Lars Wallentin, Christopher Granger
Journal: Journal of the American College of Cardiology (2014)
Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin T (the ICTUS trial): a follow-up study
Authors: Alexander Hirsch, Fons Windhausen, Jan GP Tijssen, Freek WA Verheugt, Jan Hein Cornel, Robbert J de Winter
Journal: The Lancet (2007)
Blood Sugar Levels in Patients Treated with Chlorpromazine
Authors: LUIS SCHWARZ, RODRIGO MUNOZ
Journal: American Journal of Psychiatry (1968)

The authors studied 850 patients being treated with chlorpromazine for changes in blood sugar level. While the 22 diabetic patients in the sample did not show significant modifications in their blood sugar levels, five patients developed diabetes after drug treatment. However, the latter had characteristics resembling those of persons in the general population who are prone to develop the disease.
Modified oral food challenge used with sensitization biomarkers provides more real-life clinical thresholds for peanut allergy
Authors: Katharina Blumchen, Alena Beder, John Beschorner, Frank Ahrens, Armin Gruebl, Eckard Hamelmann, Gesine Hansen, Andrea Heinzmann, Katja Nemat, Bodo Niggemann, Ulrich Wahn, Kirsten Beyer
Journal: Journal of Allergy and Clinical Immunology (2014)
Potential antimicrobial agents for the treatment of multidrug-resistant tuberculosis
Authors: Noor Alsaad, Bob Wilffert, Richard van Altena, Wiel C.M. de Lange, Tjip S. van der Werf, Jos G.W. Kosterink, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2013)

Treatment of multidrug-resistant (MDR) tuberculosis (TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration than for drug-susceptible TB patients. In order to speed up novel treatment for MDR-TB, we suggest considering expanding the indications of already available drugs. Six drugs with antimicrobial activity (phenothiazine, metronidazole, doxycycline, disulfiram, tigecycline and co-trimoxazole) are not listed in the World Health Organization guidelines on MDR-TB treatment but could be potential candidates for evaluation against Mycobacterium tuberculosis. A systematic review was conducted to evaluate antituberculous activity of these drugs against M. tuberculosis. We searched PubMed, Google Scholar and Embase for English articles published up to December 31, 2012. We reviewed in vitro, in vivo and clinical antituberculous activity of these drugs in addition to pharmacokinetics and side-effects. Of the drugs effective against actively replicating M. tuberculosis, co-trimoxazole seems to be the most promising, because of its consistent pharmacokinetic profile, easy penetration into tissue and safety profile. For the dormant state of TB, thioridazine may play a potential role as an adjuvant for treatment of MDR-TB. A strategy consisting of pharmacokinetic/pharmacodynamic studies, dose finding and phase III studies is needed to explore the role of these drugs in MDR-TB treatment.
Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells
Authors: Tatyana Grinenko, Kathrin Arndt, Melanie Portz, Nicole Mende, Marko Günther, Kadriye Nehir Cosgun, Dimitra Alexopoulou, Naharajan Lakshmanaperumal, Ian Henry, Andreas Dahl, Claudia Waskow
Journal: The Journal of Experimental Medicine (2014)

Long-term hematopoietic stem cells (HSCs [LT-HSCs]) are well known to display unpredictable differences in their clonal expansion capacities after transplantation. Here, by analyzing the cellular output after transplantation of stem cells differing in surface expression levels of the Kit receptor, we show that LT-HSCs can be systematically subdivided into two subtypes with distinct reconstitution behavior. LT-HSCs expressing intermediate levels of Kit receptor (Kit(int)) are quiescent in situ but proliferate extensively after transplantation and therefore repopulate large parts of the recipient's hematopoietic system. In contrast, metabolically active Kit(hi) LT-HSCs display more limited expansion capacities and show reduced but robust levels of repopulation after transfer. Transplantation into secondary and tertiary recipient mice show maintenance of efficient repopulation capacities of Kit(int) but not of Kit(hi) LT-HSCs. Initiation of differentiation is marked by the transit from Kit(int) to Kit(hi) HSCs, both of which precede any other known stem cell population.
Management of medical confidentiality in English professional football clubs: some ethical problems and issues
Authors: I Waddington, M Roderick
Journal: British Journal of Sports Medicine (2002)

Objective: To examine the ways in which confidential matters are dealt with in the context of the relationship between the club doctor (or physiotherapist) and the player as patient in English professional football clubs. Methods: Semistructured tape recorded interviews with 12 club doctors, 10 club physiotherapists, and 27 current and former players. A questionnaire was also sent to 90 club doctors; 58 were returned. Results: There is among club doctors and physiotherapists no commonly held code of ethics governing how much and what kind of information about players may properly be passed on to managers; associated with this, there is considerable variation from one club to another in terms of the amount and kind of information passed on to managers. In some clubs, medical staff attempt to operate more or less on the basis of the rules governing confidentiality that apply in general practice, but in other clubs, medical staff are more ready to pass on personal information about players. In some situations, this raises serious ethical questions. Conclusions: Guidelines dealing with confidentiality in practitioner-patient relationships in medical practice have long been available and have recently been restated, specifically in relation to the practice of sports medicine, by the British Olympic Association, the British Medical Association, and the Football Association. This is a welcome first step. However, if the guidelines are to have an impact on practice, detailed consideration needs to be given to ensuring their effective implementation; if this is to be achieved, consideration also needs to be given to identifying those aspects of the culture and organisation of professional football clubs that may hinder the full and effective implementation of those guidelines.
Mechanistic Influences for Mutation Induction Curves after Exposure to DNA-Reactive Carcinogens
Authors: Shareen H. Doak, Gareth J.S. Jenkins, George E. Johnson, Emma Quick, Elizabeth M. Parry, James M. Parry
Journal: Cancer Research (2007)

Abstract A mechanistic understanding of carcinogenic genotoxicity is necessary to determine consequences of chemical exposure on human populations and improve health risk assessments. Currently, linear dose-responses are assumed for DNA reactive compounds, ignoring cytoprotective processes that may limit permanent damage. To investigate the biological significance of low-dose exposures, human lymphoblastoid cells were treated with alkylating agents that have different mechanisms of action and DNA targets: methylmethane sulfonate (MMS), methylnitrosourea (MNU), ethylmethane sulfonate (EMS), and ethylnitrosourea (ENU). Chromosomal damage and point mutations were quantified with the micronucleus and hypoxanthine phosphoribosyltransferase forward mutation assays. MNU and ENU showed linear dose-responses, whereas MMS and EMS had nonlinear curves containing a range of nonmutagenic low doses. The lowest observed effect level for induction of chromosomal aberrations was 0.85 μg/mL MMS and 1.40 μg/mL EMS; point mutations required 1.25 μg/mL MMS and 1.40 μg/mL EMS before a mutagenic effect was detected. This nonlinearity could be due to homeostatic maintenance by DNA repair, which is efficient at low doses of compounds that primarily alkylate N7-G and rarely attack O atoms. A pragmatic threshold for carcinogenicity may therefore exist for such genotoxins. [Cancer Res 2007;67(8):3904–11]
Potential role of miR-9 and miR-223 in recurrent ovarian cancer
Authors: Alexandros Laios, Sharon O'Toole, Richard Flavin, Cara Martin, Lynne Kelly, Martina Ring, Stephen P Finn, Ciara Barrett, Massimo Loda, Noreen Gleeson, Tom D'Arcy, Eamonn McGuinness, Orla Sheils, Brian Sheppard, John O' Leary
Journal: Molecular Cancer (2008)

MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease.Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6) in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18) and FFPE serous ovarian tumours (n = 22). Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry.We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer.
Effect of Rising Chemotherapy Costs on the Cost Savings of Colorectal Cancer Screening
Authors: Iris Lansdorp-Vogelaar, Marjolein van Ballegooijen, Ann G. Zauber, J. Dik F. Habbema, Ernst J. Kuipers
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundAlthough colorectal cancer screening is cost-effective, it requires a considerable net investment by governments or insurance companies. If screening was cost saving, governments and insurance companies might be more inclined to invest in colorectal cancer screening programs. We examined whether colorectal cancer screening would become cost saving with the widespread use of the newer, more expensive chemotherapies.
Effects of thyroid disease on glucose oxidative metabolism in man. A compartmental model analysis
Authors: David M. Shames, Mones Berman, Stanton Segal
Journal: Journal of Clinical Investigation (1971)

Glucose oxidation to CO(2) in man at the fasted, steady state has been investigated in normal, hypothyroid, patients by monitoring the specific activity of plasma glucose and expired CO(2) after intravenous injection of glucose-1-(14)C, glucose-6-(14)C, and sodium bicarbonate-(24)C in tracer amounts. Making certain stoichiometric assumptions about the oxidation of the C-1 and C-6 carbons of glucose to CO(2), the data are incorporated into a multicompartmental model describing the kinetics of plasma glucose, plasma bicarbonate, and the conversion of glucose to CO(2) by the hexose monophosphate pathway and all other series and parallel pathways which oxidize glucose carbon to CO(2) (EMP-TCA). This formulation separates the distribution kinetics of glucose and bicarbonate from the kinetics of glucose oxidation to CO(2). It allows the calculation of a minimal fraction (varphi(t)) of glucose irreversibly oxidized to CO(2) which is based entirely on the duration of the experimental data. This calculation is independent of the extrapolative implications of the model beyond the experimental interval and of the particular model chosen to fit the data. All modeling and data fitting were performed on a digital computer with the SAAM program. Based on a 300 min experiment the analysis suggests that in hypothyroidism there is a decrease in the rate of glucose metabolized irreversibly (rhoG). There is also a decrease in the minimal fraction (varphi(300)) which is completely oxidized to CO(2) by way of the EMP-TCA. rhoG and varphi(300) are 0.56 and 0.42 mmole/min respectively as compared to 0.89 and 0.50 mmole/min respectively in normals. However, the fraction of the C-1 of glucose metabolized irreversibly which undergoes oxidation to CO(2) by the hexose monophosphate pathway (Psi) is not different from normal (0.07 and 0.07 respectively). The hyperthyroid studies suggest that rhoG and varphi(300) are within the normal range (1.01 and 0.46 mmoles/min respectively as compared to 0.89 and 0.50 mmole/min respectively in normals). However, Psi is decreased to less than half the normal value (0.03 as compared to 0.07 in normals).