tbuckley/cabot-search huggingface dataset:
Abstract 4322: The landscape of mitochondrial DNA mutations in human cancer
Authors: Young Seok Ju, Ludmil Alexandrov, Moritz Gerstung, Inigo Martincorena, Mike Stratton, Peter J. Campbell
Journal: Cancer Research (2014)

Abstract Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of human cancers. Although mitochondria in cancer cells have important roles in energy metabolism and survival, the origins and impact of somatic mutations in mitochondrial DNA (mtDNA) are unclear. Here, we provide a comprehensive analysis of somatic alterations in cancer mitochondria from 1,675 genome sequences across 31 tumor types. We identified 1,907 somatic substitutions which were mainly C:G&amp;gt;T:A and T:A&amp;gt;C:G. These mutations exhibited dramatic replicative strand bias, being almost all C&amp;gt;T and A&amp;gt;G on the mitochondrial heavy strand. This strand-asymmetric mitochondrial mutational signature is different from those found in nuclear cancer genomes but is similar to processes shaping human mtDNA sequence over evolutionary time. The number of mtDNA mutations showed considerable heterogeneity across tumor types, being significantly higher in tumors from gastrointestinal and hepatobiliary systems. With respect to selection, observed missense mutations were nearly neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation showed evidence of negative selection and were more frequently heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria, and is fundamentally linked to mtDNA replication. Citation Format: Young Seok Ju, Ludmil Alexandrov, Moritz Gerstung, Inigo Martincorena, ICGC Breast Cancer Group; ICGC Chronic Myeloid Disorders Group; ICGC Prostate Cancer Group, Mike Stratton, Peter J. Campbell. The landscape of mitochondrial DNA mutations in human cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4322. doi:10.1158/1538-7445.AM2014-4322
Nitric oxide metabolite flux during exercise in pulmonary arterial hypertension
Authors: William Oldham, Allison Janocha, Paul Pappagianopoulos, Serpil Erzurum, Aaron Waxman, Gregory Lewis, David Systrom
Journal: European Respiratory Journal (2011)

Introduction:  Exercise-induced pulmonary arterial hypertension (PAH) is a clinically important stage in the spectrum of PAH. The pathophysiology of abnormal pulmonary vascular responses to exercise is poorly characterized. Endogenous nitric oxide (NO) is an important mediator of vasodilation and accumulating data suggests impaired NO signaling PAH.   Aims:  The objective was to test the hypothesis that changes in stable NO metabolites (NOx) in blood during exercise in patients with resting or exercise-induced PAH would differ from NOx in individuals with normal exercise pulmonary arterial pressures. Patients were selected from a population referred to the MGH Cardiopulmonary Exercise Lab for invasive incremental cardiopulmonary exercise testing with pulmonary and radial artery catheters. Simultaneous samples of arterial (a) and mixed venous (mv) blood at rest, peak exercise, and one hour post-exercise were obtained from 10 patients with PAH (VO2max  30 mmHg, and PVR >80 dyne s cm -5 ) and 10 controls (VO2max and Qtmax both >80% predicted). These were analyzed for [NOx] using chemiluminescence. Data are median [interquartile ranges]. Comparisons used the Mann-Whitney test.   Results:  NOx mv  increased from rest to exercise in controls (45%, [4, 77], p=0.02), but not in PAH (0%, [-27, 15], p=0.97).  NOx a  increased in both groups (11% [-2, 26]  v  7% [-7, 40], p=0.80). NOx flux [Qtmax × (mv – a [NOx])] in controls was greater than PAH (370% [-100, 4869]  v  -96% [-460, 6], p=0.04).  There were no differences in [NOx] during recovery.   Conclusions:  Normal pulmonary vasodilation and recruitment during exercise may be dependent on NOx bioavailability in mixed venous blood.
Abdominal Aortic Calcification Detected With routine Vertebral Fracture Assessment: A Strong Predictor of Cardiovascular Events
Authors: Reza Golestani, Riemer H. Slart, Clark J. Zeebregts, Rudi A. Dierckx, Henrikus H. Boersma, Hans L. Hillege, Rene A. Tio
Journal: Circulation (2009)
Pegylated Interferon vs Standard Interferon for Chronic Hepatitis C
Authors: Daniel L Menkes
Journal: JAMA (2005)

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 2728: Nonadherence to Prescribed Medications Mediates the Link between Anxiety and Event-Free Survival in Patients with Heart Failure
Authors: Marla J De Jong, Debra K Moser, Misook L Chung, Jia-Rong Wu
Journal: Circulation (2008)

Anxiety has been linked to adverse outcomes for patients with cardiac disease but the mechanism for this relationship is unknown. Nonadherence to prescribed medications is common in heart disease, particularly heart failure (HF), and may mediate the relationship between anxiety and outcomes. To determine if nonadherence to prescribed medications mediates any relationship between anxiety and clinical outcomes in patients with HF. Patients (N=147; age 61±11 yrs, 44% female, 59% NYHA class III/IV) with chronic HF were followed 389±324 days for clinical events (composite of death, emergency department visit, or hospitalization). Patients completed the anxiety subscale of the Brief Symptom Inventory at baseline. Objective evidence of medication adherence was measured with the Medication Event Monitoring System. Survival and regression analyses were used to test whether medication nonadherence mediated any association between anxiety and outcomes. Patients with highest anxiety had shorter event-free survival than patients with lower anxiety (Fig. ). After adjusting for age, gender, and NYHA class in Cox regression, high anxiety predicted (OR 2.4; p=.001) clinical events. Anxiety predicted medication doses taken (p=.01) and days correct doses taken (p=.008). Medication doses taken (p=.01) and days dose taken (p=.008) also predicted clinical outcomes. Medication nonadherence mediated the relationship between high anxiety and worse outcomes. This is the first study to show that medication nonadherence links anxiety and clinical outcomes. Interventions that decrease anxiety may improve both medication adherence and outcomes.
AEROSOLISED PENTAMIDINE AS SOLE THERAPY FOR PNEUMOCYSTIS CARINII PNEUMONIA IN PATIENTS WITH ACQUIRED IMMUNODEFICIENCY SYNDROME
Authors: A. Bruce Montgomery, JohnM. Luce, Joan Turner, EmilT. Lin, RobertJ. Debs, KevinJ. Corkery, ElisaN. Brunette, PhilipC. Hopewell
Journal: The Lancet (1987)
Abstract 432: BIN3 is a novel 8p21 tumor suppressor gene that regulates the attachment checkpoint in epithelial cells
Authors: Netonia Marshall, Felix Sanchez, David Llobet, Ruth Rodriguez Barrueco, Veronica Castro, Dylan Kotlia, Maira Pires, Patricia Villagrasa, Preeti Putcha, Ramon Parsons, Dana Pe'er, Jose Silva
Journal: Cancer Research (2014)

Abstract An important characteristic of multicellular organisms is the control that the tissue architecture exerts on the fate of individual cells. Epithelial cells sense their location through interactions with the extracellular matrix (ECM) and remove themselves by programmed cell death (anoikis) when those interactions are disturbed. Importantly, anoikis is a line of defense that has to be circumvented by cancerous epithelial cells to be able to leave their home environment and establish long distance metastases. Here, by combining a genome-wide RNAi screen and a novel algorithm to study copy number alterations (ISAR-DEL), we identify the Bridging Integrator-3 (BIN3) as a novel 8p21 tumor suppressor gene whose inactivation promotes escape from anoikis in epithelial cancers. Mechanistically, we link the tumor suppression function of BIN3 to its ability to relocate to the cell membrane after cell detachment and to induce a proapoptotic cascade. This death signaling is mediated by CDC42 activation of the P38-α stress pathway and the consequent accumulation of the apoptotic facilitator BimEL. Our results identify BIN3 as a novel epithelial tumor suppressor gene, provide novel insights on the mechanisms of attachment tumor suppressor checkpoint and highlight the importance of anoikis escape in driving cell transformation and metastasis in human cancer. Note: This abstract was not presented at the meeting. Citation Format: Netonia Marshall, Felix Sanchez, David Llobet, Ruth Rodriguez Barrueco, Veronica Castro, Dylan Kotlia, Maira Pires, Patricia Villagrasa, Preeti Putcha, Ramon Parsons, Dana Pe'er, Jose Silva. BIN3 is a novel 8p21 tumor suppressor gene that regulates the attachment checkpoint in epithelial cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 432. doi:10.1158/1538-7445.AM2014-432
Limitations of standardized skin surface biopsy in measurement of the density of Demodex folliculorum. A case report
Authors: None Forton, None Song
Journal: British Journal of Dermatology (1998)

Standardized skin surface biopsy (SSSB) is an appropriate method for measuring the density of Demodex folliculorum (Dd). Nevertheless, the observation of a clinical case demonstrates that, contrary to what was presumed before, a single SSSB can fail to collect the complete biotope of the mite. This could give rise to false negative results regarding the measurement of Dd.
Exome sequencing of multiple metastases from a lethal prostate cancer reveals BRCA1 deficiency and additional somatic alterations which suggest alternate therapeutic options
Authors: Michael L. Nickerson, Kate McGee Im, Michael Dean, G. Steven Bova
Journal: Clinical Cancer Research (2010)

Abstract Exome libraries were prepared from five metastatic tumors and healthy tissue from an Ashkenazi Jewish man who died from metastatic prostate cancer. A total of 6.77 × 109 bases were sequenced using a 454 FLX. Germline alteration and somatic loss of heterozygosity of the BRCA1 tumor suppressor gene were observed. Novel, somatic variants in the catalytic domain of two kinases and alteration of two oncogenes were also potential drivers of this cancer. We identified an insertion in the TMPRSS2 gene in addition to fusion with ERG. Alteration of several signaling pathways was predicted as a result of a surprising combination of germline and somatic alterations. Clonal as well as subclonal variants were identified that allow a ‘natural history’ of this individual's cancer to be described. Several alterations, including BRCA1 loss, suggest therapeutic options that may have been effective in this patient. This talk is also presented as Poster B17.
91. Universal Purification of AAV Serotypes 1-5 Modified To Contain a Heparin Binding Epitope
Authors: Susan M. Faust, Dawn E. Bowles, Scott E. Cunningham, Joseph E. Rabinowitz, R. Jude Samulski
Journal: Molecular Therapy (2004)

To directly evaluate the utility of distinct serotypes of adeno-associated virus (AAV) for gene therapy applications, it will be necessary to purify each in a similar manner. The methodology to obtain highly purified rAAV2 for use in clinical trials has been established using heparin column affinity binding in conjunction with iodixanol gradients. With the exception of AAV3, the other serotypes of AAV do not bind heparin. Recently the amino acids responsible for the ability of AAV2 to bind to heparin were identified (Kern et al 2003, J Virol 77:11072–81) and tested in the context of rAAV5 (Opie et al 2003, J Virol 77:6995–7006). To assess whether all serotypes could be modified to bind heparin, the AAV2 amino acids R585 R588 and A590 were substituted into the homologous positions in serotypes 1, 3, 4, and 5 to generate the pxr1RRA, pxr3RRA, pxr4RRA, and pxr5RRA plasmids. These helper vectors were then used to produce recombinant eGFP virus which were initially purified by either cesium chloride or iodixanol gradients followed by dialysis.
Spatial and Nonspatial Influences on the TQ-ST Segment Deflection of Ischemia
Authors: Roger P. Holland, Harold Brooks, Barbara Lidl
Journal: Journal of Clinical Investigation (1977)

Spatial and nonspatial aspects of TQ-ST segment mapping were studied with the solid angle theorem and randomly coded data from 15,000 electrograms of 160 anterior descending artery occlusions each of 100-s duration performed in 18 pigs. Factors analyzed included electrode location, ischemic area and shape, wall thickness, and increases in plasma potassium (K(+)). Change from control in the TQ-ST recorded at 60 s (DeltaTQ-ST) was measured at 22 ischemic (IS) and nonischemic (NIS) epicardial sites overlying right (RV) and left (LV) ventricles. In IS regions, DeltaTQ-ST decreased according to LV > septum > RV and LV base > LV apex. In NIS regions, LV sites had negative (Neg) DeltaTQ-ST which increased as LV IS border was approached. However, RV NIS had positive (Pos) DeltaTQ-ST which again increased as RV IS border was approached. With large artery occlusion IS area increased 123+/-18%, DeltaTQ-ST at IS sites decreased (-38.1+/-3.6%), and sum of DeltaTQ-ST at IS sites increased by only 67.3+/-10.3%. In RV NIS Pos DeltaTQ-ST became Neg. With increased K(+), DeltaTQ-ST decreased proportionately to log K(+) (r = 0.97+/-0.01) at IS and NIS sites on the epicardium and precordium. TQ-ST at 60 s was obliterated when K(+) = 8.7+/-0.2 mM. All findings were significant (P < 0.005) and agreed with the solid angle theorem. Thus, a transmembrane potential difference and current flow at the IS boundary alone are responsible for the TQ-ST. Nonspatial factors affect the magnitude of transmembrane potential difference, while spatial factors alter the position of the boundary to the electrode site.
Evidence of increased DNA methylation of the androgen receptor gene in occipital hair follicles from men with androgenetic alopecia
Authors: J.E. Cobb, N.C. Wong, L.W. Yip, J. Martinick, R. Bosnich, R.D. Sinclair, J.M. Craig, R. Saffery, S.B. Harrap, J.A. Ellis
Journal: British Journal of Dermatology (2011)

Journal Article Evidence of increased DNA methylation of the androgen receptor gene in occipital hair follicles from men with androgenetic alopecia Get access J.E. Cobb, J.E. Cobb Department of Physiology, University of Melbourne, Victoria 3010, Australia Search for other works by this author on: Oxford Academic Google Scholar N.C. Wong, N.C. Wong Developmental Epigenetics, Environmental and Genetic Epidemiology Research, Murdoch Childrens Research Institute, Flemington Road, Parkville, Victoria 3052, Australia Search for other works by this author on: Oxford Academic Google Scholar L.W. Yip, L.W. Yip Department of Dermatology, St Vincent's Hospital, Victoria 3065, Australia Search for other works by this author on: Oxford Academic Google Scholar J. Martinick, J. Martinick New Hair Clinic, 627 Chapel Street, South Yarra, Victoria 3141, Australia Search for other works by this author on: Oxford Academic Google Scholar R. Bosnich, R. Bosnich National Hair Institute, 104 Canterbury Road, Middle Park, Victoria 3206, Australia Search for other works by this author on: Oxford Academic Google Scholar R.D. Sinclair, R.D. Sinclair Department of Dermatology, St Vincent's Hospital, Victoria 3065, Australia Search for other works by this author on: Oxford Academic Google Scholar J.M. Craig, J.M. Craig Developmental Epigenetics, Environmental and Genetic Epidemiology Research, Murdoch Childrens Research Institute, Flemington Road, Parkville, Victoria 3052, Australia Search for other works by this author on: Oxford Academic Google Scholar R. Saffery, R. Saffery Developmental Epigenetics, Environmental and Genetic Epidemiology Research, Murdoch Childrens Research Institute, Flemington Road, Parkville, Victoria 3052, Australia Search for other works by this author on: Oxford Academic Google Scholar S.B. Harrap, S.B. Harrap Department of Physiology, University of Melbourne, Victoria 3010, Australia Search for other works by this author on: Oxford Academic Google Scholar J.A. Ellis J.A. Ellis Department of Physiology, University of Melbourne, Victoria 3010, Australia E‐mail: justine.ellis@mcri.edu.au Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 1, 1 July 2011, Pages 210–213, https://doi.org/10.1111/j.1365-2133.2011.10335.x Published: 01 July 2011
Peptide immunotherapy for allergic diseases
Authors: M. Larché
Journal: Allergy (2007)

Specific allergen immunotherapy has been widely practised for almost 100 years. Whilst this approach is disease‐modifying and efficacious, the use of whole allergen preparations is associated with an unacceptably high prevalence of allergic adverse events during treatment. Many approaches to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity are under development. One such approach is the use of short synthetic peptides which represent major T‐cell epitopes of the allergen. Major potential advantages of this approach include markedly reduced capacity to cross‐link immunoglobulin‐E and activate mast cells and basophils, and ease of manufacture and standardization. Promising results in preclinical studies have led to the translation of this approach to clinical studies in humans. Peptide immunotherapy is currently under development for allergic and autoimmune diseases.
Abstract 931: Role of IKKα in K-ras-driven lung carcinogenesis
Authors: Na-Young Song, Jami Willette-Brown, Mahesh Dalta, Yinling Hu
Journal: Cancer Research (2014)

Abstract IKKα, one of subunits of the IKK complex, is required for the epidermal homeostasis. We previously demonstrated that keratin 5-specific deletion of IKKα induces spontaneous skin squamous cell carcinomas (SCCs) in mice. Interestingly, IKKα kinase dead knockin (IKKαK44A/K44A, KA) mice spontaneously develop lung SCCs which is associated with increased inflammation and IKKα reduction. Thus, IKKα downregulation is crucial for the SCC formation in skin and lung. Here, we attempted to verify whether IKKα inactivation plays a role in the development of lung adenocarcinomas (ADCs) as well. We have crossed between KA mice and K-rasG12D oncogenic mutant (Kras) mice. Then, these IKKαK44A/K44A;K-rasG12D (KA;Kras) mice were intratracheally treated with adenovirus carrying the cre recombinase gene to activate K-ras oncogene. At 4.5 months after intratracheal injection, the lung weight was significantly increased in KA;Kras compared to Kras mice. Moreover, the lungs of KA;Kras mice showed increased bronchial epithelial cells and Ki67-positive cells in the bronchial regions. At 7 months after treatment, lung tumors in KA;Kras mice were larger compared to tumors in Kras mice. Finally, KA;Kras mice had shorter life span due to breathing problems. KA;Kras mice started to die at around 20 weeks after injection, while KR mice started to die from around 30 weeks. To confirm whether IKKα reduction promotes K-ras-driven lung carcinogenesis, we generated IKKαf/f (FF) mice crossed with Kras (FF;Kras) mice. Similar to KA;Kras, FF;Kras mice showed significant increase of lung weight, hyperproliferative bronchial abnormalities, Ki-67-positive cells in the bronchial regions and the number of large tumors at 4 months following treatment compared with Kras only group. Taken together, these data suggest that IKKα downregulation promotes K-ras-driven lung tumorigenesis and plays an important role in lung ADCs as well as in SCCs. The underlying molecular mechanism needs to be further investigated. Citation Format: Na-Young Song, Jami Willette-Brown, Mahesh Dalta, Yinling Hu. Role of IKKα in K-ras-driven lung carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 931. doi:10.1158/1538-7445.AM2014-931
Peripartum Cardiomyopathy
Authors: Jayasree Pillarisetti, Ashok Kondur, Anas Alani, Madhu Reddy, Madhuri Reddy, James Vacek, Carl P Weiner, Edward Ellerbeck, Theodore Schreiber, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2014)
Use of Antibiotics and Risk of Cancer
Authors: Neil H Shear, Donald A Redelmeier, Jeffrey P Callen
Journal: JAMA (2004)

To the Editor: Dr Velicer and colleagues reported an association between use of antibiotics and increased risk of breast cancer. We have several concerns about the design of this study. First, because the authors did not obtain data about other prescription medications, they could not establish that the effect was specifically due to antibiotics. Second, although the regression analyses were adjusted for age and duration of insurance enrollment, the authors apparently did not adjust for other documented confounders, such as body mass index, family history of breast cancer, and age at menarche. Third, other confounding factors that might be correlated with both the need for antibiotics and the risk of breast cancer were not analyzed (eg, smoke exposure, weight fluctuations, and use of ethanol). Finally, the results are inconsistent with data from animal studies that show no relationship between extended antibiotic exposure and breast cancer. Until these issues are addressed we believe that the judicious use of antibiotics is still safe in appropriate patients regardless of the patient’s individual risk of breast cancer.