tbuckley/cabot-search huggingface dataset:
Use of a tissue biomarker panel to predict which men with a rising PSA post-definitive prostate cancer therapy will have systemic progression
Authors: R. B. Jenkins, T. Nakagawa, T. Kollmeyer, B. Morlan, E. Bergstrahl, B. Davis, G. Klee, K. V. Ballman
Journal: Journal of Clinical Oncology (2007)

5017 Background: The majority of men with prostate cancer are diagnosed with cancers with low mortality. Such men are treated with radical prostatectomy, external beam radiotherapy, or brachytherapy and followed by serum PSA evaluations. Some men with a rising PSA therapy will have local recurrence or metastasis, but many will have no other evidence of recurrent disease other than a rising PSA. The PSA doubling time has been used to determine which of these men deserve adjuvant hormonal ablation, radiation therapy, or observation. We hypothesize that additional biomarkers will predict which men with a rising PSA post-definitive therapy would benefit from additional therapy. Methods: We designed a custom array containing 526 RNA targets whose expression has been reported to be altered in association with prostate cancer progression. We included targets from Mayo Clinic prostate cancer research. Together with a second commercial array, 530 genes implicated in prostate cancer progression and 420 other cancer-related genes were evaluated. A case-control design was used to test the association of the expression results with outcome. Cases were men post-radical prostatectomy who developed systemic progression within 5 years after PSA recurrence (N=213). Controls were matched men post-radical prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years (N=213). Results: Of 426 eligible patients, paraffin blocks were available on 418 (98.1%). RNA was prepared from all 418 blocks, and both arrays were both successful on 405 (96.9%) RNAs. Upon univariate analysis, 40 genes were highly significantly over- or under-expressed in the cases versus controls (1x10 -22 &lt; p &lt; 1x10 -7 ). Recursive partitioning (RP) selected 4 genes (TPX2, FAM13C1, TOPO2A and TSP2) that distinguished cases from controls. Random Forest analysis selected 24 genes (including 3 of the RP 4). A multivariable ROC analysis using these 24 genes generated an AUC of 0.80 (95% CI: 0.75–0.84). Conclusions: A specific gene expression pattern was significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence. No significant financial relationships to disclose.
Self-management experiences in adults with mild-moderate psoriasis: an exploratory study and implications for improved support
Authors: S.J. Ersser, F.C. Cowdell, S.M. Latter, E. Healy
Journal: British Journal of Dermatology (2010)

Journal Article Self‐management experiences in adults with mild–moderate psoriasis: an exploratory study and implications for improved support Get access S.J. Ersser, S.J. Ersser Centre for Wellbeing and Quality of Life, Room 110, Royal London House, Bournemouth University, Christchurch Road, Bournemouth BH1 3LT, U.K. Correspondence: Steven J. Ersser. E‐mail: sersser@bournemouth.ac.uk Search for other works by this author on: Oxford Academic Google Scholar F.C. Cowdell, F.C. Cowdell Centre for Wellbeing and Quality of Life, Room 110, Royal London House, Bournemouth University, Christchurch Road, Bournemouth BH1 3LT, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.M. Latter, S.M. Latter School of Health Sciences Search for other works by this author on: Oxford Academic Google Scholar E. Healy E. Healy Department of Dermatopharmacology, University of Southampton, Southampton, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 5, 1 November 2010, Pages 1044–1049, https://doi.org/10.1111/j.1365-2133.2010.09916.x Published: 01 November 2010
Energetic and Functional Abnormalities in Human Heart Failure are Associated with Increased Ventricular and Skeletal Muscle Mitochondrial Uncoupling Protein-3 Levels
Authors: Andrew W Johnson, Cameron Holloway, Lindsay Edwards, Chandi Ratnatunga, Ravi Pillai, Stefan Neubauer, Rhys Evans, Kieran Clarke
Journal: Circulation (2011)

Heart failure patients have decreased cardiac phosphocreatine/ATP (PCr/ATP) ratios and skeletal muscle PCr recovery rates, suggesting mitochondrial dysfunction, but the cause is unknown. Plasma non...
457. Fibronectin Peptide Reduces the Immune Response to Adenovirus and Enhances Transgene Expression
Authors: Dinesh Singh, Suresh K. Mittal
Journal: Molecular Therapy (2004)

Preexisting immunity against human adenoviruses (HAd) limits the efficiency of transduction of HAd vectors in humans. In addition, development of a vector-specific immune response following the first inoculation with a HAd vector further lowers vector uptake following readministration. We investigated the usefulness of porcine adenovirus serotype 3 (PAd3)-based vectors as a supplement to HAd vectors. Here we demonstrate that preexisting HAd-specific neutralizing antibodies in humans do not cross-neutralize PAd3. In order to generate E1A-deleted PAd3 vectors, an E1-complementing cell line of porcine origin was produced. To compare transduction efficiencies of PAd3 and human adenovirus type 5 (HAd5) vectors, PAd-GFP (E1A-deleted PAd3 vector expressing green fluorescent protein; GFP) and HAd-GFP (E1-deleted HAd5 vector expressing GFP) were generated. PAd-GFP and HAd-GFP transduced human cell lines with comparable efficiencies. Both vectors efficiently transduced murine MT1A2 breast cancer cell line, while PAd-GFP transduced murine NIH-3T3 fibroblast cell line significantly better (P<0.05) than HAd-GFP. These results suggest that PAd3 vector system would be a promising supplement to HAd vectors as a delivery vehicle for recombinant vaccines and gene therapy applications.
Global variation in clinical profile, management, and post‐discharge outcomes among patients hospitalized for worsening chronic heart failure: findings from the <scp>ASTRONAUT</scp> trial
Authors: Stephen J. Greene, Gregg C. Fonarow, Scott D. Solomon, Haris Subacius, Aldo P. Maggioni, Michael Böhm, Eldrin F. Lewis, Faiez Zannad, Mihai Gheorghiade
Journal: European Journal of Heart Failure (2015)
Distinguishing mental illness in primary care
Authors: H. Middleton
Journal: BMJ (2000)

Two studies in the BMJ last year make challenging reading set alongside one another. Kessler et al reported that over half the patients attending general practice surgeries are depressed,1 and the Norwegian naturalistic treatment study of depression in general practice concluded that the best treatment for depression in primary care is a combination of antidepressant medication and counselling.2 Read uncritically, these findings imply that half of all general practice patients should be taking antidepressants and undergoing counselling. Clearly few people would agree with this, but the apparent folly does draw attention to a gap in our understanding of mental ill health in primary care.3

Uncertainties about the best way to provide for such patients, and indeed questions about the propriety of doing so at all within the NHS, have a long history. These uncertainties largely revolve around differences between medical and sociological approaches to psychological distress. The medical approach argues that such distress reflects an underlying illness which merits treatment. The sociological perspective argues that it is the consequence of a failure to respond adaptively to social challenge. The former focuses …
Metformin inhibits TGF-b-induced myofibroblast differentiation through AMPK activation
Authors: Naoki Takasaka, Jun Araya, Yusuke Kurita, Kenji Kobayashi, Saburo Ito, Hiroshi Wakui, Yutaka Yoshii, Shunsuke Minagawa, Jun Kojima, Hiromichi Hara, Takanori Numata, Kenichiro Shimizu, Makoto Kawaishi, Yumi Kaneko, Katsutoshi Nakayama, Kazuyoshi Kuwano
Journal: European Respiratory Journal (2014)

Introduction:  Accumulation of profibrotic myofibroblasts is a crucial step for fibrotic remodeling in idiopathic pulmonary fibrosis (IPF), and transforming growth factor (TGF)-bhas a key regulatory role in myofibroblast differentiation. Reactive oxygen species (ROS) has been proposed to be involved in the mechanism for TGF-b-induced myofibroblast differentiation. Metformin is a biguanide antidiabetic medication and its pharmacological action is mediated through the activation of AMPK, which regulates not only energy homeostasis but also stress responses including ROS. Hence, we hypothesized that metformin may modulate TGF-b-induced myofibroblast differentiation through the regulation of ROS production.  Methods:  Using human lung fibroblast (LFB), western blotting (WB) of alpha-smooth muscle actin (SMA) was performed to evaluate TGF-b-induced myofibroblast differentiation in the presence and absence of metformin. AMPK activation was detected by showing phosphorylation via WB. AMPK was inhibited by siRNA-mediated knockdown. CM-H2DCFDA was used to evaluate intracellular ROS production.  Results:  TGF-b induced myofibroblast differentiation, which was clearly inhibited by metformin treatment. AMPK inhibition illustrates that metformin-mediated activation of AMPK was responsible for suppression of TGF-b-induced myofibroblast differentiation. Intriguingly, metformin also suppressed TGF-b-induced NADPH oxidase 4 (NOX4) expression and ROS production via AMPK activation. Conclusion: Metformin suppresses NOX4 expression and ROS production via AMPK activation, resulting in inhibition of TGF-b-induced myofibroblast differentiation. Therefore, metformin may also be used for the treatment of IPF.
Atlas der normalen Histologie und mikroskopischen Anatomie des Menschen
Authors: Ernst von Herrath, Serge Semenovic Abramow
Journal: JAMA (1952)

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 Publications 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
Abstract #LB-147: A crucial role of cancer stem cell for the regulation of immunosuppressive tumor escape via Treg induction
Authors: Kenji Chamoto, Daiko Wakita, Takayuki Ohkuri, Yuji Togashi, Hidemitsu Kitamura, Takashi Nishimura
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

To investigate the differential role of regulatory T cell (Treg; CD4+ Foxp3+ T cell) in immunosuppressive mechanisms mediated by squamous cell carcinoma (SCC) and sarcoma, which were both induced by 3-methylcholantrane (MCA), we analyzed the changes of number of Treg cells 2 weeks after the primary tumor cell line inoculation. The number of Treg was significantly increased in draining lymph node (DLN) of SCC-bearing mice compared with sarcoma-bearing mice. In order to assess the imunosupressive effects of Treg, we depleted Treg by pre-treatment of anti-CD25 mAb and monitored the subsequent tumor growth. Surprisingly, the administration of anti-CD25 mAb did not caused the growth inhibition of SCC, while complete inhibition was induced in sarcoma-bearing mice through activation of host immune responses. As a possible explanation for the refractoriness of SCC, we found that Treg was rapidly restored in mice inoculated with SCC but nor sarcoma after anti-CD25 mAb injection. The rapid recovery of Treg in SCC-bearing mice was explained by the fact that active form of TGF-\#946;, known as a factor to induce Treg, was highly produced by carcinoma compared with sarcoma. Indeed, blocking TGF-\#946; signaling in vivo by administration of anti-TGF-\#946; mAb into Treg depleted-mice caused a significant inhibition of Treg recovery in SCC-inoculated mice and induced a complete rejection of the tumor. We also pursued the characteristics of the major TGF-\#946;-high producing tumor cells among SCC cells, which might play a crucial role in controlling carcinoma-induced immunosuppression via TGF-\#946; dependent Treg accumulation. We focused on a pivotal role of CD133+ cancer stem cell in SCC for the induction of CD4+ CD25+ FOXP3+ Treg cells. Here, we initially demonstrated that CD133+ CMC-1 cancer stem cells, but not CD133- CMC-1 cells are pivotal controller of tumor escape via inducing Treg cells. CD133+ CMC-1 cancer stem cells produce higher levels of TGF-\#946; and promote the accumulation of Treg cell at draining lymph node. Thus, cancer stem cells inhibit antitumor immunity through TGF-\#946;-dependent Treg induction. We are now trying to develop a novel tumor-targeting immunotherapy against cancer stem cells.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-147.
Abstract 15567: Glutamine Regulates Cardiac Stem Cell Metabolism and Competency
Authors: Joshua K Salabei, Pawel K Lorkiewicz, Candice R Holden, Matthew A Harbeson, Qianhong Li, Roberto Bolli, Aruni Bhatnagar, Bradford G Hill
Journal: Circulation (2014)

Objective:  Cardiac stem cells (CSCs) increase myocardial function in the damaged heart; however, the mechanisms that contribute to their reparative qualities remain poorly understood. Because intermediary metabolism likely integrates characteristics involved in CSC competency, we examined CSC metabolism in the undifferentiated and early differentiated cell states.   Methods and Results:  CSCs (c-kit+/lin-) isolated from mouse heart were positive for mesenchymal stem cell antigens (e.g., CD24/CD29/CD90.2/CD105) and relatively devoid of markers of differentiated cardiovascular cells. Early differentiation of CSCs increased the expression of smooth muscle, endothelial, and/or cardiomyocyte markers up to 60-fold, and increased expression of paracrine factors such as adiponectin (p   Conclusions:  CSCs have mesenchymal stem cell characteristics and rely primarily upon glutamine to meet metabolic demands. Differentiation increases the expression of not only markers of cardiovascular cells, but also that of paracrine factors and the glutamine transporter. Interventions that increase glutamine uptake may improve CSC therapeutic efficacy by enhancing CSC metabolism and proliferation.
Abstract 13846: The Relationship of Platelet Function Measurements with Bleeding Outcomes During Long-term Treatment with Dual Antiplatelet Therapy in Medically Managed NSTE-ACS Patients
Authors: Jan H Cornel, E. M Ohman, Benjamin Neely, Joseph A Jakubowski, Deepak L Bhatt, Harvey D White, Diego Ardissino, Keith A Fox, Dorairaj Prabhakaran, Paul W Armstrong, David Erlinge, Paul A Gurbel, Matthew T Roe
Journal: Circulation (2014)

Introduction: The relationship of low “on-treatment” platelet reactivity to longitudinal risks of major bleeding following acute coronary syndromes (ACS) has not been clearly delineated. Methods: We analyzed 2428 patients with non-ST-elevation ACS (NSTE ACS) from the TRILOGY ACS trial who were managed without revascularization and had platelet reactivity measurements (P2Y12 reaction units [PRUs]) collected in a platelet function substudy. Patients received aspirin + prasugrel (10 mg/d; 5 mg/d for those ≥75 y or &lt;75 y and &lt;60 kg) or clopidogrel (75 mg/d). Non-CABG severe/moderate GUSTO bleeding and non-CABG TIMI major/minor bleeding were ascertained through 30 months. Contal’s method was used to investigate whether a PRU cut point could distinguish high vs low bleeding risk. Multivariable Cox proportional hazard models were used to evaluate the association between PRU and time to first bleed. Results: Through 30 months, there were 27 GUSTO severe/moderate bleeds and 37 TIMI major/minor bleeds, with gastrointestinal bleeding the most common. Baseline characteristics were stratified by tertiles of PRU values at 5 d, and significant differences were seen across tertiles (Table). Unadjusted bleeding rates appeared highest among those in the lowest PRU tertile but no reliable PRU cut point was found that significantly distinguished bleeding risk. Unadjusted analyses showed continuous measures of PRUs were not associated with GUSTO (HR=1.00, 95% CI: 0.96-1.04) or TIMI bleeding (HR=1.03, 95% CI: 0.99-1.06). This relationship did not change after multivariable adjustment. Conclusions: Among NSTE-ACS patients managed without revascularization and receiving dual antiplatelet therapy, PRU values were not significantly associated with long-term bleeding risk. The relatively small number of bleeding events accrued limited study power, but these results suggest that low “on-treatment” platelet reactivity does not independently predict post-ACS bleeding risk.
Hepatitis B Vaccination for Newborns—Reply
Authors: Ronda J. Oram
Journal: JAMA (2001)

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 Publications 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
Radio: 28 Minutes to Save the NHS
Authors: N. Steel
Journal: BMJ (2002)

BBC Radio 4, Wednesdays at 11 pm, 6 to 27 February 2002

The quality of health care is causing a major crisis throughout the Western world. In the United Kingdom we love to bash the NHS, but have little to compare it with, in the way that Americans can compare managed care with fee-for-service. They moan about the evils of managed care, but are gradually realising, in the words of quality expert Bob Brook from US think tank RAND, that “managed care is not the problem, quality is.”

In …
274. Combination of a Second Generation Genetically Modified Herpes Simplex Virus 1 (HSV 1) with Paclitaxel in the Treatment of Breast Cancer In Vitro
Authors: Catherine M. Tone, Dawn M. Cardoza, Robert H. Carpenter, Ruxandra Draghia-Akli
Journal: Molecular Therapy (2004)

Top of pageAbstract
Geriatric and cancer-afflicted patients often experience decreased quality of life with cachexia, anemia, anorexia, and decreased activity level. We have studied the possibility that a myogenic plasmid that expresses growth hormone releasing hormone (GHRH) can prevent and/or treat these conditions. We administered plasmid to 17 geriatric and 5 cancer-afflicted companion dogs with an average age of 10.5 ± 1.0 and 11.3 ± 0.6 years at enrollment, respectively. Effects of the treatment were documented for at least 180 days post-treatment, with 10 animals followed for more than 1 year post treatment, on average 444 ± 40 days. Treated dogs showed increased IGF-I levels, and increases in scores for weight, activity level, exercise tolerance and appetite. No adverse effects associated with the GHRH plasmid treatment were found. Most importantly, the overall assessment of the quality of life of the treated animals increased. Hematological parameters such as red blood cell count, hematocrit, and hemoglobin concentrations were improved and maintained within their normal ranges. We conclude that intramuscular injection of a GHRH-expressing plasmid is both safe and capable of improving the quality of life in animals for an extended period of time in the context of aging and disease. The observed anabolic and hematological responses to a single dose of this plasmid treatment may also be beneficial in geriatric patients or patients with cancer-associated anemia and/or cachexia Figure 1.
Abstract 893: Metabolomic profiling of APCΔ14/+ mice maintained on a methyl donor deficient diet reveals alterations to methionine and fatty acid metabolism associated with cancer protection
Authors: Matthew P. Hanley, Daniel W. Rosenberg
Journal: Cancer Research (2015)

Abstract Our laboratory has previously demonstrated that administration of a diet deficient in methyl donor nutrients (folic acid, methionine, choline and vitamin B12) reduces tumor multiplicity by greater than 95% in ApcMin/+ mice. However, the mechanism by which this dramatic cancer protection is afforded is unknown. To begin to identify the metabolic consequences of methyl donor deficiency, we have conducted an LC/MS-based metabolic profiling analysis of colonic mucosa collected from ApcΔ14/+ mice fed a methyl donor deficient (MDD) diet for 17 weeks. Methyl donor deficiency causes significant alterations to a number of key metabolic pathways, including those involved in the methionine cycle, fatty acid oxidation, and tryptophan catabolism. We observed significant reductions in methionine (65% reduction, p&amp;lt;0.001) and betaine (70% reduction, p&amp;lt;0.001), accompanied by large increases in homocysteine (88.6-fold increase, p&amp;lt;0.001) and S-adenosylmethionine (17.2-fold increase, p&amp;lt;0.001), confirming that dietary methyl donor deficiency alters one-carbon metabolites in the colon. MDD mice were found to have reduced levels of acyl-carnitines and free carnitine (58% reduction, p&amp;lt;0.001). Additionally, we detected a reduction in the critical metabolic component, acetyl CoA, suggesting decreased transport of fatty acids into the mitochondria for use in fatty acid oxidation (FAO). Finally, we observed changes in the mucosal levels of tryptophan (32% reduction, p = 0.02), kynurenine (2.8-fold increase, p = 0.008) and indolepropionate (5.1-fold increase, p = 0.005), that were retained for seven weeks beyond active methyl donor deficiency. Taken together, these findings suggest that dietary methyl donor deficiency significantly disrupts the methionine cycle, inhibits fatty acid transport and oxidation, and may induce long-term changes to tryptophan metabolism. This study has improved our understanding of the molecular mechanisms underlying the cancer protection conveyed by dietary methyl donor deficiency and has identified metabolic pathways that are candidate targets for chemopreventive intervention. Citation Format: Matthew P. Hanley, Daniel W. Rosenberg. Metabolomic profiling of APCΔ14/+ mice maintained on a methyl donor deficient diet reveals alterations to methionine and fatty acid metabolism associated with cancer protection. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 893. doi:10.1158/1538-7445.AM2015-893