tbuckley/cabot-search huggingface dataset:
The contribution of sulphate reducing bacteria and 5-aminosalicylic acid to faecal sulphide in patients with ulcerative colitis
Authors: M C L Pitcher
Journal: Gut (2000)

<h3>BACKGROUND</h3> Butyrate oxidation within the colonocyte is selectively inhibited by hydrogen sulphide, reproducing the metabolic lesion observed in active ulcerative colitis. <h3>AIMS</h3> To study generation of hydrogen sulphide by sulphate reducing bacteria (SRB) and the effects of 5-aminosalicylic acid (5-ASA) in patients with ulcerative colitis in order to identify a role of this noxious agent in pathogenesis. <h3>PATIENTS</h3> Fresh faeces were obtained from 37 patients with ulcerative colitis (23 with active disease) and 16 healthy controls. <h3>METHODS</h3> SRB were enumerated from fresh faecal slurries and measurements made of sulphate reducing activity, and sulphate and hydrogen sulphide concentrations. The effect of 5-ASA on hydrogen sulphide production was studied in vitro. <h3>RESULTS</h3> All controls and patients with active ulcerative colitis carried SRB and total viable counts were significantly related to the clinical severity grade. SRB were of two distinct types: rapidly growing strains (desulfovibrios) which showed high sulphate reduction rates, present in 30% of patients with ulcerative colitis and 44% of controls; and slow growing strains which had little activity. In vitro, 5-ASA inhibited sulphide production in a dose dependent manner; in patients with ulcerative colitis not on these drugs faecal sulphide was significantly higher than in controls (0.55 versus 0.25 mM, p=0.027). <h3>CONCLUSIONS</h3> Counts and carriage rates of SRB in faeces of patients with ulcerative colitis are not significantly different from those in controls. SRB metabolism is not uniform between strains and alternative sources of hydrogen sulphide production exist in the colonic lumen which may be similarly inhibited by 5-ASA. The evidence for hydrogen sulphide as a metabolic toxin in ulcerative colitis remains circumstantial.
De Novo Synthesis of Myocardial Adenine Nucleotides in the Rat
Authors: HEINZ-GERD ZIMMER, Christian Trendelenburg, Helmut Kammermeier, Eckehart Gerlach
Journal: Circulation Research (1973)

De novo synthesis of adenine nucleotides was measured in rat hearts in situ and in isolated perfused rat hearts under normal conditions and during recovery from asphyxia or ischemia. Using l- 14 C-glycine as the precursor substrate, rates of de novo synthesis were determined from the total radioactivity of adenine nucleotides and from the mean specific activity of intracellular glycine. The rate of de novo synthesis of adenine nucleotides was 8.4±1.42 nmoles/g hour -1 in the heart in situ and 1.3±0.12 nmoles/g hour -1 in the isolated perfused heart. De novo synthesis of adenine nucleotides increased almost 100% in the heart in situ and about 580% in the isolated perfused heart during the first hour of recovery from asphyxia or ischemia. This acceleration is regarded as an adaptive process contributing to the postanoxic restoration of normal adenine nucleotide levels. Possible biochemical mechanisms that might be involved in the stimulation of the de novo pathway are a release of feedback inhibition of 5-phosphoribosyl-1-pyrophosphate amidotransferase, an enhanced synthesis of 5-phosphoribosyl-1-pyrophosphate, and an alternate way of 5-phosphoribosyl-amine formation.
Analysis of the host pharmacogenetic background for prediction of outcome and toxicity in diffuse large B-cell lymphoma treated with R-CHOP21
Authors: D Rossi, S Rasi, S Franceschetti, D Capello, A Castelli, L De Paoli, A Ramponi, A Chiappella, E M Pogliani, U Vitolo, I Kwee, F Bertoni, A Conconi, G Gaidano
Journal: Leukemia (2009)
A developmental model of number representation
Authors: Karin Kucian, Liane Kaufmann
Journal: Behavioral and Brain Sciences (2009)

Abstract We delineate a developmental model of number representations. Notably, developmental dyscalculia (DD) is rarely associated with an all-or-none deficit in numerosity processing as would be expected if assuming abstract number representations. Finally, we suggest that the “generalist genes” view might be a plausible – though thus far speculative – explanatory framework for our model of how number representations develop.
Prognostic factors for a subsequent basal cell carcinoma: implications for follow-up
Authors: C.A. van Iersel, H.V.N. van de Velden, C.D.J. Kusters, P.H.M. Spauwen, W.A.M. Blokx, L.A.L.M. Kiemeney, M.J.P. Gerritsen
Journal: British Journal of Dermatology (2005)

Conflict of interest: None declared. Sir, Patients with a basal cell carcinoma (BCC) are prone to develop more BCCs. Prognostic factors for a second BCC may be important for follow‐up practices but valid prognostic studies are unavailable. Previous studies have short follow‐up,1–3 failed to perform 'time‐to‐failure' analyses,1, 2, 4, 5 combined patient groups with primary and recurrent BCCs6 or first and second or higher BCCs,3, 6–8 or did not perform a multivariable analysis.9 We investigated the risk and prognostic factors for a subsequent BCC after the first primary BCC. We retrospectively reviewed patient charts and blindly reviewed histology slides of 237 patients who had a conventional excision of their first primary BCC of the skin at the Departments of Dermatology or Plastic Surgery at the Radboud University Nijmegen Medical Centre, the Netherlands, between 1993 and 1998. Patients are routinely followed for 5 years. Patients with a follow‐up of less than 5 years were contacted by telephone and asked if they had had a skin examination by a physician or had currently any signs of recurrent BCC [a BCC diagnosis following the first (solitary or multiple) BCC(s) and occurring in the scar area of the previously excised primary BCC] or subsequent BCC [a BCC diagnosis following the first (solitary or multiple) BCC(s) and occurring at another body site]. In case of doubt, patients were invited to the outpatient clinic. We determined the 5‐year risk of a subsequent BCC or recurrence with Kaplan–Meier time‐to‐failure analyses. To avoid double counting, the 5‐year risk for subgroups of four patient‐related and seven tumour‐related factors was determined in the patient group with only one BCC at diagnosis, and compared with log‐rank statistics. Follow‐up was censored at date of last contact with the patient. With Cox multivariable analyses we estimated the independent prognostic value of several factors.
Determinants of New-Onset Diabetes Among 19,257 Hypertensive Patients Randomized in the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm and the Relative Influence of Antihypertensive Medication
Authors: Ajay K. Gupta, Bjorn Dahlof, Joanna Dobson, Peter S. Sever, Hans Wedel, N.R. Poulter
Journal: Diabetes Care (2008)

The purpose of this study was to determine the baseline predictors of new-onset diabetes (NOD) in hypertensive patients and to develop a risk score to identify those at high risk of NOD.Among 19,257 hypertensive patients in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) who were randomly assigned to receive one of two antihypertensive regimens (atenolol +/- thiazide or amlodipine +/- perindopril), 14,120 were at risk of developing diabetes at baseline. Of these, 1,366 (9.7%) subsequently developed NOD during median follow-up of 5.5 years. A multivariate Cox model was developed to identify the independent predictors of NOD and individual risk scores.NOD was significantly associated with an increase in baseline fasting plasma glucose (FPG), BMI, serum triglycerides, and systolic blood pressure. In contrast, amlodipine +/- perindopril in comparison with atenolol +/- thiazide treatment (hazard ratio 0.66 [95% CI 0.59-0.74]), high HDL cholesterol, alcohol use, and age >55 years were found to be significantly protective factors. FPG was the most powerful predictor with risk increasing by 5.8 times (95% CI 5.23-6.43) for each millimole per liter rise >5 mmol/l. The risk of NOD increased steadily with increasing quartile of risk score, with a 19-fold increase (95% CI 14.3-25.4) among those in the highest compared with those in the lowest quartile. The model showed excellent internal validity and discriminative ability.Baseline FPG >5 mmol/l, BMI, and use of an atenolol +/- diuretic regimen were among the major determinants of NOD in hypertensive patients. The model developed from these data allows accurate prediction of NOD among hypertensive subjects.
Marketing of Personalized Cancer Care on the Web: An Analysis of Internet Websites
Authors: Stacy W. Gray, Angel Cronin, Elizabeth Bair, Neal Lindeman, Vish Viswanath, Katherine A. Janeway
Journal: JNCI Journal of the National Cancer Institute (2015)

Internet marketing may accelerate the use of care based on genomic or tumor-derived data. However, online marketing may be detrimental if it endorses products of unproven benefit. We conducted an analysis of Internet websites to identify personalized cancer medicine (PCM) products and claims. A Delphi Panel categorized PCM as standard or nonstandard based on evidence of clinical utility. Fifty-five websites, sponsored by commercial entities, academic institutions, physicians, research institutes, and organizations, that marketed PCM included somatic (58%) and germline (20%) analysis, interpretive services (15%), and physicians/institutions offering personalized care (44%). Of 32 sites offering somatic analysis, 56% included specific test information (range 1-152 tests). All statistical tests were two-sided, and comparisons of website content were conducted using McNemar's test. More websites contained information about the benefits than limitations of PCM (85% vs 27%, P < .001). Websites specifying somatic analysis were statistically significantly more likely to market one or more nonstandard tests as compared with standard tests (88% vs 44%, P = .04).
Synergistic Effect of Oncogenic <i>RET</i> and Loss of <i>p18</i> on Medullary Thyroid Carcinoma Development
Authors: Wendy van Veelen, Carola J.R. van Gasteren, Dennis S. Acton, David S. Franklin, Ruud Berger, Cornelis J.M. Lips, Jo W.M. Höppener
Journal: Cancer Research (2008)

Abstract Activating mutations in the RET proto-oncogene are associated with both familial and sporadic medullary thyroid carcinoma (MTC) development; however, the genetic mechanisms underlying MTC tumorigenesis remain largely unknown. Recently, we have identified somatic inactivating mutations in the cell cycle inhibitor gene P18 in human MTC, which coincided with activating RET mutations, suggesting a role for loss of P18 in combination with oncogenic RET in the multistep process of MTC development. Therefore, we crossed transgenic mice expressing oncogenic RET (RET2B) with mice lacking p18 (and p27, another cell cycle inhibitor) and monitored MTC development. RET2B;p18+/− mice and RET2B;p18−/− mice developed MTC with a highly increased incidence compared with their corresponding single mutant littermates. In addition, expression of oncogenic RET causes an earlier age of onset and larger MTCs in p18−/−;p27+/− mice. In a subset of MTCs of RET2B;p18+/−(;p27+/−) mice, p18Ink4c expression was completely lost. This loss of p18Ink4c expression correlated with higher proliferation rates as well as with larger MTCs, indicating that loss of p18 in combination with oncogenic RET not only increases the risk for MTC development but also enhances MTC progression. Our data strongly indicate that oncogenic RET and loss of p18 cooperate in the multistep tumorigenesis of MTC. [Cancer Res 2008;68(5):1329–37]
Exploring the Benefits and Limits of Highly Active Antiretroviral Therapy
Authors: Richard D'Aquila
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Expression of Uncoupling Protein-2 in Human Colon Cancer
Authors: Masayoshi Horimoto, Murray B. Resnick, Tamako A. Konkin, Justin Routhier, Jack R. Wands, György Baffy
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Cancer cell survival depends on adaptive mechanisms that include modulation of oxidative stress. One such mechanism may be via up-regulation of uncoupling protein-2 (UCP2), a mitochondrial inner membrane anion carrier recently found to provide cytoprotection in nontumor cells by acting as a sensor and negative regulator of reactive oxygen species production. We hypothesized that UCP2 expression may be increased in colon cancer as part of tumor adaptation. Experimental Design: UCP2 expression was characterized by real-time polymerase chain reaction and Western blotting using paired human colon adenocarcinoma and peritumoral specimens. Oxidant production was characterized by tissue malondialdehyde levels. Tissue microarrays constructed of 107 colon adenocarcinomas as well as representative specimens of hyperplastic polyps and tubular adenomas were used for UCP2 immunohistochemistry. Results: UCP2 mRNA and protein levels were 3- to 4-fold higher in adenocarcinomas, and UCP2 mRNA levels showed significant correlation with increased tumor tissue malondialdehyde contents. Immunohistochemistry on tissue microarrays showed positive staining for UCP2 in most adenocarcinomas (86.0%); positive staining for UCP2 was seen less often in tubular adenomas (58.8%) and rarely seen in hyperplastic polyps (11.1%). Conclusions: UCP2 expression is increased in most human colon cancers, and the level of expression appears to correlate with the degree of neoplastic changes. These findings may foster the idea that UCP2 is part of a novel adaptive response by which oxidative stress is modulated in colon cancer.
Targeting ETV1 in Gastrointestinal Stromal Tumors: Tripping the Circuit Breaker in GIST?
Authors: Anette Duensing
Journal: Cancer Discovery (2015)

Abstract Summary: Activating mutations in the KIT or PDGFRA receptor tyrosine kinase genes are the key oncogenic drivers in the majority of gastrointestinal stromal tumors (GIST), but novel results now show that aberrant kinase signaling is potentiated by a positive feedback circuit that involves the ETS transcription factor ETV1. Targeting ETV1 can disrupt this circuit and represents a promising new therapeutic approach for the treatment of GISTs. Cancer Discov; 5(3); 231–3. ©2015 AACR. See related article by Ran and colleagues, p. 304
Quantitation of cell-free DNA and RNA in plasma during tumor progression in rats
Authors: Dolores C García-Olmo, María G Picazo, Inmaculada Toboso, Ana I Asensio, Damián García-Olmo
Journal: Molecular Cancer (2013)

To clarify the implications of cell-free nucleic acids (cfNA) in the plasma in neoplastic disease, it is necessary to determine the kinetics of their release into the circulation.To quantify non-tumor and tumor DNA and RNA in the plasma of tumor-bearing rats and to correlate such levels with tumor progression, we injected DHD/K12-PROb colon cancer cells subcutaneously into syngenic BD-IX rats. Rats were sacrificed and their plasma was analyzed from the first to the eleventh week after inoculation.The release of large amounts of non-tumor DNA into plasma was related to tumor development from its early stages. Tumor-specific DNA was detected in 33% of tumor-bearing rats, starting from the first week after inoculation and at an increasing frequency thereafter. Animals that were positive for tumor DNA in the plasma had larger tumors than those that were negative (p = 0.0006). However, the appearance of both mutated and non-mutated DNA fluctuated with time and levels of both were scattered among individuals in each group. The release of non-tumor mRNA was unaffected by tumor progression and we did not detect mutated RNA sequences in any animals.The release of normal and tumor cfDNA into plasma appeared to be related to individual-specific factors. The contribution of tumor DNA to the elevated levels of plasma DNA was intermittent. The release of RNA into plasma during cancer progression appeared to be an even more selective and elusive phenomenon than that of DNA.
Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial
Authors: Robert A Hauser, Ann Hsu, Sherron Kell, Alberto J Espay, Kapil Sethi, Mark Stacy, William Ondo, Martin O'Connell, Suneel Gupta
Journal: The Lancet Neurology (2013)
Modification of the cerebrovascular response to noradrenaline by bile duct ligation.
Authors: D S Bloom, B H Eidelman, T A McCalden
Journal: Gut (1975)

The effects of intracarotid infusions of noradrenaline on the cerebral vasculature were studied in seven baboons with bile duct ligation. Infusion of 8 mug and 16 mug/min of noradrenaline resulted in a significant decrease in cerebral blood flow in the jaundiced animals. In normal baboons, these doses produced cerebrovascular dilatation. These results indicate that there is an increased cerebrovascular sensitivity to noradrenaline in the obstructive jaundice which follows bile duct ligation. It is postulated that noradrenaline smooth muscle uptake mechanisms are disturbed allowing a greater concentration of the amine at the receptor sites.
Rhinitis and onset of asthma: a longitudinal population-based study
Authors: Rafea Shaaban, Mahmoud Zureik, David Soussan, Catherine Neukirch, Joachim Heinrich, Jordi Sunyer, Matthias Wjst, Isa Cerveri, Isabelle Pin, Jean Bousquet, Deborah Jarvis, Peter G Burney, Françoise Neukirch, Bénédicte Leynaert
Journal: The Lancet (2008)
Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas
Authors: M. Peyre, S. Cartalat-Carel, D. Meyronet, D. Ricard, A. Jouvet, J. Pallud, K. Mokhtari, J. Guyotat, E. Jouanneau, M.-P. Sunyach, D. Frappaz, J. Honnorat, F. Ducray
Journal: Neuro-Oncology (2010)

Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated.
Genetic risk factors for anterior cruciate ligament ruptures:<i>COL1A1</i>gene variant
Authors: M Posthumus, A V September, M Keegan, D O’Cuinneagain, W Van der Merwe, M P Schwellnus, M Collins
Journal: British Journal of Sports Medicine (2009)

Anterior cruciate ligament (ACL) ruptures are considered the most severe injury sustained in sports. Although various intrinsic and extrinsic risk factors have been identified, the exact aetiology of the injury is not yet fully understood. Recently, the gene encoding for the alpha1 chain of type I collagen (COL1A1) has been shown to be associated with cruciate ligament ruptures and shoulder dislocations.To determine whether the functional Sp1 binding site polymorphism within intron 1 of the COL1A1 gene is associated specifically with ACL ruptures in an independent population.117 Caucasian participants with surgically diagnosed ACL ruptures, and 130 Caucasian physically active controls without any history of previous ligament or tendon injuries were recruited for this case-control genetic association study. All participants were genotyped for the COL1A1 Sp1 binding site polymorphism (G/T; rs1800012).The rare TT genotype was significantly (p = 0.031, OR = 0.08, 95% CI <0.01 to 1.46) under-represented in the ACL group (0 out of 117, 0%), compared with the controls (6 out of 130, 4.6%).The TT genotype of the COL1A1 Sp1 binding site polymorphism was significantly under-represented in South African participants with ACL ruptures. We propose that this sequence variant be the first specific genetic element to be included in multifactorial models developed to understand the aetiology and risk factors for ACL rupture.
Myeloid cell expression of the RNA-binding protein HuR protects mice from pathologic inflammation and colorectal carcinogenesis
Authors: Anthie Yiakouvaki, Marios Dimitriou, Ioannis Karakasiliotis, Christina Eftychi, Stamatis Theocharis, Dimitris L. Kontoyiannis
Journal: Journal of Clinical Investigation (2011)

The innate immune response involves a variety of inflammatory reactions that can result in inflammatory disease and cancer if they are not resolved and instead are allowed to persist. The effective activation and resolution of innate immune responses relies on the production and posttranscriptional regulation of mRNAs encoding inflammatory effector proteins. The RNA-binding protein HuR binds to and regulates such mRNAs, but its exact role in inflammation remains unclear. Here we show that HuR maintains inflammatory homeostasis by controlling macrophage plasticity and migration. Mice lacking HuR in myeloid-lineage cells, which include many of the cells of the innate immune system, displayed enhanced sensitivity to endotoxemia, rapid progression of chemical-induced colitis, and severe susceptibility to colitis-associated cancer. The myeloid cell-specific HuR-deficient mice had an exacerbated inflammatory cytokine profile and showed enhanced CCR2-mediated macrophage chemotaxis. At the molecular level, activated macrophages from these mice showed enhancements in the use of inflammatory mRNAs (including Tnf, Tgfb, Il10, Ccr2, and Ccl2) due to a lack of inhibitory effects on their inducible translation and/or stability. Conversely, myeloid overexpression of HuR induced posttranscriptional silencing, reduced inflammatory profiles, and protected mice from colitis and cancer. Our results highlight the role of HuR as a homeostatic coordinator of mRNAs that encode molecules that guide innate inflammatory effects and demonstrate the potential of harnessing the effects of HuR for clinical benefit against pathologic inflammation and cancer.