tbuckley/cabot-search huggingface dataset:
Abstract 5294: Sequestration of Prosurvival Akt Pathway by Reductive Stress Underlies hR120GCryAB Protein Aggregation Cardiomyopathy in Mice
Authors: Rajasekaran Namakkal Soorappan, Huali Zhang, Shannon Odelberg, Ivor J Benjamni
Journal: Circulation (2008)

Recent genetic studies of protein aggregation R120GCryAB cardiomyopathy in mice have implicated a novel ‘toxic’ gain-of-function mechanism linked to increased G6PD activity and levels of reduced glutathione (GSH), termed ‘reductive stress.’ Because the intercrosses between hR120GCryAB High Tg and G6PD-deficient (20% normal activity) rescues the phenotype, we hypothesized that the pathogenesis of hR120GCryAB cardiomyopathy are causally linked to redox sensitive signaling transduction pathways controlling cardiac hypertrophy and failure. We examined the temporo-spatial effects on activation of the major stress-dependent survival pathways. Human R120GCryAB expression in mice induces modest activation of total and phosphospecific p38 and ERK1/2 kinases but significantly increases phospho-specific JNK1/2 in vivo. Both total and phosphospecific AKT1/2 expression were similarly increased in hR120GCryAB and hR120GCryAB/G6PDmut in vivo. In contrast, immunohistochemical analysis indicated cytosolic Akt expression co-localized with in large protein aggregates, whereas G6PD deficiency completely prevented protein aggregation, indicating hR120GCryAB-induced reductive stress governs conformational states of PI3-kinase/AKT signaling in compartment-specific manner. Consistent with this notion, the cytosolic abundance of forkhead FOXO3a, a phosphorylation-dependent downstream target of nuclear AKT1/2 signaling, was decreased significantly in R120GCryAB High Tg heart homogenates and reciprocally increased in hR120GCryAB/G6PDmut in vivo. To investigate the critical roles of AktCys60 and AktCys77 residues, which form disulfide bond pairing under oxidized conditions, we next performed site-directed mutagenesis and demonstrated that redox-insensitive Akt mutants (AktC60A and AktC77A, respectively) were exclusively localized in the nucleus when expressed transiently in H9c2 myocytes. Redox-dependent mechanisms play a key role in the cardiotoxicity associated with hR120GCryAB-induced reductive stress. Furthermore, G6PD inhibition is a novel therapeutic strategy for mitigating cardiac hypertrophy and heart failure in hR120GCryAB cardiomyopathy.
Abstract 2156: In-Stent Restenosis after Sirolimus-Eluting Stent Implantation is Related to Coronary Stent Fracture
Authors: SY Lee, MH Kim, CM Ahn, JS Kim, DH Choi, YS Jang, NS Chung, PK Min, YW Yoon, BK Hong
Journal: Circulation (2007)

Background and objectives : It has been reported in few studies about relationship between sirolimus-eluting stent (SES) fracture and in-stent restenosis (ISR). Therefore, authors investigated clinical characteristics of the SES fracture and the association with ISR. Subjects and Methods : From December 2003 to February 2006, implantation and follow-up coronary angiography(CAG) for 796 sirolimus-eluting stents were carried out in Severance hospital. We reviewed clinical, procedural and structural factors which might affect SES fracture and ISR. Results : Twenty four fractures after 796 SES implantation were identified by follow-up coronary angiography, sixteen cases in the left anterior descending artery and eight in the right coronary artery. The median time interval from stent implantation to follow up CAG was 9.0 months [range: 2 ~ 30 months]. No statistical difference was found in stent diameter (fracture group 3.06 ± 0.32 mm vs non-fracture group 3.08 ± 0.31 mm, P=0.778). Length of fractured stents was longer than non-fractured stents (30.29 ± 4.16 mm vs 24.51 ± 6.18 mm, P&lt;0.001). The binary ISR rate in the stent fracture group was higher compared to non-fracture group (50% vs 4.4%, p &lt; 0.001). Predictors for ISR estimated by multivariate analysis were stent fracture (OR=33.6, p &lt; 0.001), stent diameter less than 3.0 mm (OR=2.84, p =0.015) and stent length over 28 mm (OR = 3.10, p = 0.023). Among twelve cases which had both binary restenosis and stent fracture, eight cases were treated by balloon angioplasty or additional stent implantation considering the condition of patients. Conclusion : Stent fracture may be one of the crucial mechanisms of ISR after implantation of SES. However, further studies in larger scale are required to define the incidence, predisposing factors, and clinical outcomes of SES fracture.
Trichinellosis acquired in Nunavut, Canada in September 2009: meat from grizzly bear suspected
Authors: S Houzé, T Ancelle, R Matra, C Boceno, Y Carlier, A  A Gajadhar, J Dupouy-Camet
Journal: Eurosurveillance (2009)

Five cases of trichinellosis with onset of symptoms in September 2009, were reported in France, and were probably linked to the consumption of meat from a grizzly bear in Cambridge Bay in Nunavut, Canada. Travellers should be aware of the risks of eating raw or rare meat products in arctic regions, particularly game meat such as bear or walrus meat.
Equity in the NHS: Equity in community care
Authors: L Challis, M Henwood
Journal: BMJ (1994)

The implementation of the NHS and Community Care Act 1990 made local authority social services departments responsible for the organisation and funding of support and care in the community. This development took effect at the same time as a blurring of the boundaries between health and social care. One consequence is that the relevance of equity (a guiding principle of the 1946 National Health Service Act, but relatively lacking from the 1948 National Assistance Act, the foundation of many social services) has come to be more keenly appreciated within personal social services. Equity questions arise in community care over the distribution of public resources between different client groups, income groups, generations, and localities. Moreover, no mechanisms exist to monitor the trends that emerge from different ways that people get access to care. Yet there is a risk that substantial divisive consequences may occur, particularly between generations.
Abstract 503: Paracrine Factors from Cardiac Fibroblasts Slow Conduction Velocity and Prolong the Action Potential Duration of Cardiomyocytes
Authors: Dawn Pedrotty, Rebecca Klinger, Nenad Bursac
Journal: Circulation (2007)

By acting as passive current sinks or conduction obstacles, cardiac fibroblasts directly slow conduction and increase electrical anisotropy in fibrotic cardiac tissue, leading to increased arrhythmogenicity. We studied if indirect paracrine action by cardiac fibroblasts can alter electrical properties and related gene expression in cardiomyocytes. Confluent cardiomyocyte cultures were incubated for 24 h in serum-free defined media conditioned 24 h by cardiac fibroblasts. Age-matched unconditioned cultures served as controls. The cell membrane potentials were optically mapped at 504 sites using voltage sensitive dye, Di-4 ANEPPS. Remarkably, a two-fold decrease in conduction velocity and three-fold increase in action potential duration were measured. Observed changes in conditioned cultures were not caused by increased cell apoptosis or fibroblast proliferation. Fresh medium with concentrated fibroblast paracrine factors induced the same effect. Consistent with electrophysiological changes, conditioned cultures had decreased mRNA expression for fast sodium (SCN5A, 3.8 fold), inward rectifier potassium (Kir2.1, 6.6 fold) and transient outward potassium (Kv4.3, below detection limit) channels, but unchanged expression of Connexin 43 and 45. Expressions of myosin heavy chain-beta and alpha were respectively increased 17 fold and decreased 2.2 fold. Importantly, media conditioned by the same number of fibroblasts in the presence of cardiomyocytes had no effect on cardiac electrical properties, suggesting that under normal conditions, cardiomyocytes may secrete protective factors that inhibit the negative paracrine action of cardiac fibroblasts. Isochrone maps and action potential traces of control (A1) and fibroblast conditioned cardiac cultures (A2). Pulse sign (Π) denotes pacing site and circles represent recording sites. Comparative conduction velocity (B1) and action potential duration (B2) values given. The gene expression of the conditioned cardiac cells reported relative to the gene expression of the control cultures (C). In conditioned cultures, expression of Kv4.3 was below the detectable level.
SB939: a potent, orally-active HDAC inhibitor for the treatment of haematologic malignancies and solid tumors
Authors: Kanda Sangthongpitag, Haishan Wang, Walter Stunkel, Zahid Bonday, Khee Chuan Goh, Xukun Wang, Xiaofeng Wu, Changyong Hu, Eric Sun, Michael Entzeroth, Venkatesh Reddy, Evelyn Goh, Pauline Yeo, Chen Chien-Shing, Gedas Greicius, Sven Pettersson, Kantharaj Ethirajulu, Jeanette Wood
Journal: Clinical Cancer Research (2007)

C14   Inhibitors of histone deacetylases (HDAC) are emerging as an exciting new class of anti-cancer drugs that arrest tumor growth by modulating the expression of a number of genes involved in cell proliferation, cell cycle progression, cell survival and differentiation.  SB939 is a novel, potent and selective HDAC inhibitor with improved efficacy and tolerability compared to other HDAC inhibitors currently in clinical trials. SB939 inhibits class I and II HDAC enzymes with high selectivity over other zinc binding enzymes. SB939 exerts potent anti-proliferative and apoptosis-inducing effects against a broad range of human tumor cell lines and primary cells from cancer patients, with highest potencies against malignancies of haematological origin. In cancer cell lines, SB939 increases acetylation of histone3 (H3) and tubulin, increases the expression of p21, and reduces phosphorylation of retinoblastoma protein (pRb), resulting in cell cycle arrest and leading to apoptotic cell death. SB939 has excellent pharmacokinetic and pharmacodynamic (PK/PD) properties and tolerability after oral administration in preclinical species. SB939 is a highly soluble and permeable compound and does not undergo active P-glycoprotein transport. It significantly and dose-dependently inhibits tumor growth in mouse models of human haematological and solid tumors. In a nude mice model of colorectal cancer (HCT116), enriched tumor concentrations of SB939 and increased acetylation of histone H3 were observed in tumor tissue for up to 24 h after a once daily oral dose (50-100 mg/kg), confirming long-lasting and potent target inhibition. PK/PD parameters that best described the anti-tumor activity of HDAC inhibitors in the HCT116 tumor model have been identified and will be used to help select the dose of SB939 in Phase I clinical trials.  SB939 is currently in Phase I clinical studies in Singapore and North America after having completed pre-clinical development.
Neurologic Manifestations of General Diseases
Authors: John A. Aita
Journal: JAMA (1964)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Re: Adrian Pilatz, Hamid Hossain, Rolf Kaiser, et al. Acute Epididymitis Revisited: Impact of Molecular Diagnostics on Etiology and Contemporary Guideline Recommendations. Eur Urol 2015;68:428–35
Authors: Takashi Deguchi, Mitsuru Yasuda, Shin Ito
Journal: European Urology (2015)
Assessment of Viet Nam veterans for posttraumatic stress disorder in Veterans Administration disability claims
Authors: Roland M. Atkinson, Robin G. Henderson, Landy F. Sparr, Shirley Deale
Journal: American Journal of Psychiatry (1982)

Since the Veterans Administration (VA) authorized compensation and other benefits for posttraumatic stress disorder, delayed type, in October 1980, the agency has received an increasingly large number of claims--mainly from Viet Nam veterans--for this disorder. An unprecedented challenge of the adequacy of psychiatric disability evaluation in the VA has thus been created. The authors describe efforts in one large program to meet this challenge and review 12 problems in the diagnostic process. Cooperation of all parties in claims transactions, thorough claimant assessment, reliance on DSM-III criteria and methods and consultation with examiners are essential principles for this work.
Abstract 10246: Comparison of Low and High Dose Intracoronary Adenosine and Acetylcholine in Women Undergoing Coronary Reactivity Testing
Authors: Puja K Mehta, John W Petersen, R. David Anderson, Delia Johnson, Chrisandra Shufelt, Bruce Samuels, Saibal Kar, Babak Azarbal, Eileen Handberg, Kamlesh Kothawade, Carl J Pepine, C. Noel Bairey Merz
Journal: Circulation (2011)
Robust expression of CCR3 as a single basophil selection marker in flow cytometry
Authors: O. V. Hausmann, T. Gentinetta, M. Fux, S. Ducrest, W. J. Pichler, C. A. Dahinden
Journal: Allergy (2010)

Basophil activation tests (BAT) rely on different combinations of basophil selection and activation markers. Whereas activation markers, especially CD63, are widely validated, the most suitable and robust marker for basophil selection is still a matter of debate.Comparison of cell surface expression of two commonly used basophil selection markers (IgE, CD123/HLA-DR) with CCR3 in an unselected group of atopic and nonatopic donors in resting and activated basophils.EDTA blood of 94 healthy adults, about half of them atopic by history, was analyzed using two different staining strategies: anti-CD123-PE/anti-HLA-DR-PerCP/anti-lin1-FITC and anti-IgE-FITC/anti-CD3-PerCP/anti-CCR3-PE. Additionally 40 pollen-allergic patients were recruited for the assessment of CCR3 expression after basophil activation.In resting basophils, cell surface expression of the three basophil selection markers was most constant for CCR3. IgE gating strategy showed the highest variation and up to 80% of nonbasophils in the selected gate in certain donors. During basophil activation, a shift of the mean fluorescence intensity for CCR3 toward the lower third of the CCR3-positive population could be demonstrated, but neither were CCR3-positive cells significantly lost for further analysis nor was differentiation between CCR3-positive and CCR3-negative cell populations hampered by this shift.CCR3 is a stable and highly expressed basophil selection marker, independent of the atopic background or basophil activation state and allows an accurate identification of basophils without need of a second marker. The basophil markers CD123/HLA-DR and IgE showed significantly higher interindividual variability in cell surface expression and are therefore less suited as selection markers.
Abstract #2306: Radiosensitizing potential of T lymhocytes: expanded CD4+ and CD8+ T cells display distinct patterns of IFN-gamma expression and radiosensitizing activity
Authors: Mark De Ridder, Heng Jiang, Valeri Verovski, Kalun Law, Christinne Monsaert, Dirk Van den Berge, Dirk Verellen, Guy Storme
Journal: Cancer Research (2009)

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

Purpose: It is well documented that activation, expansion and differentiation of naive T lymphocytes results in the appearance of perforin+/granzyme B+/IFN-gamma+ effectors. This study examined whether expanded T lymphocytes may radiosensitize tumor cells through the release of IFN-gamma, and whether CD4+ and CD8+ T cells display distinct IFN-gamma and radiosensitizing profiles. Methods: Naive T lymphocytes from Balb/c mice were activated with IL12 plus IL18. T-cell expansion was achieved by a 2-day priming with bound anti-CD3 plus soluble anti-CD28 antibodies, further growth in the presence of IL-2 for 7 days, and restimulation through CD3/CD28. CD8+ and CD4+ T cells were selected by immunomagnetic MACS beads and analyzed for intracellular IFN-gamma by FACS, RT-PCR and ELISA. To radiosensitize target EMT-6 tumor cells, subconfluent cultures were incubated with activated T cells or their conditioned medium (CM), irradiated at 5-15 Gy in 1% oxygen, and reseeded for colony formation assay. The expression of inducible nitric oxide synthase (iNOS), a downstream target of IFN-gamma in tumor cells, was analyzed by RT-PCR and production of NO/nitrite. Results: Expanded and restimulated T cells displayed a perforin+/granzyme B+/IFN-gamma+ phenotype, and enhanced the radiosensitivity of hypoxic EMT-6 cells up to 1.8-fold at an effector/target ratio 1:1. Similar effects were induced by purified CD8+ T cells, which produced IFN-gamma at high levels (2.9 ng/103 cells), and expressed 80-90% IFN-gamma+ phenotype. In contrast, CD4+ T cells revealed reduced levels (by 3-5-times) of IFN-gamma expression and secretion, and a 1.4-fold radiosensitization only. Similar radiosensitizing effects could be induced by CM diluted 1:30, and were abrogated by anti-IFN-gamma antibodies and by aminoguanidine, a metabolic inhibitor of iNOS. These results indicate that the observed radiosensitization does not require direct immune-tumor cell interaction, but is linked to the release of IFN-gamma, a potent activator of iNOS in tumor cells. In line, iNOS up-regulation in EMT-6 cells was confirmed at transcriptional and protein levels. Naive T cells secreted marginal levels of IFN-gamma+ and did not affect the radiosensitivity of EMT-6 tumor cells. Following activation with IL12/IL18, naive T cells showed 8-10% IFN-gamma+ phenotype, and were able to radiosensitize EMT-6 cells at an effector/target ratio 10:1, or at a dilution of CM 1:3. Conclusion: The radiosensitizing potential of activated T cells is primarily linked to IFN-gamma+ CD8+ T cells, and is drastically increased along T-cell expansion.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2306.
Biomarkers for Primary Sjögren’s Syndrome
Authors: Weiqian Chen, Heng Cao, Jin Lin, Nancy Olsen, Song Guo Zheng
Journal: Genomics Proteomics & Bioinformatics (2015)

Abstract Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease with exocrine gland dysfunction and multi-organ involvement. Recent progress in understanding the pathogenesis of pSS offers an opportunity to find new biomarkers for the diagnosis and assessment of disease activity. Screening noninvasive biomarkers from the saliva and tears has significant potential. The need for specific and sensitive biomarker candidates in pSS is significant. This review aims to summarize recent advances in the identification of biomarkers of Sjögren syndrome, trying to identify reliable, sensitive, and specific biomarkers that can be used to guide treatment decisions.
Immunogenicity of reduced dose priming schedules of serogroup C meningococcal conjugate vaccine followed by booster at 12 months in infants
Authors: David Pace, Ameneh Khatami, Jennifer McKenna, Danielle Campbell, Simon Attard-Montalto, Jacqueline Birks, Merryn Voysey, Catherine White, Adam H R Finn, Emma Macloed, Saul N Faust, Alison Louise Kent, Paul T Heath, Ray Borrow, Matthew D Snape, Andrew J Pollard
Journal: BMJ (2015)
Author's Reply: Treatment of Pain
Authors: K. M. Foley
Journal: CA A Cancer Journal for Clinicians (1987)

has misunderstood the purpose of my article, which was to discuss the treatment of cancer pain before, during, and following the use of anticancer modal ities.There is no question that radiation oncologists play a major role in the man agement of cancer pain, and there is de tailed literature to support this statement.However, I would argue that there are in sufficient published data to suggest that ra diation therapy can successfully manage 80 percent of pain problems.For example, bone metastases, visceral pain, and tumor infiltration of nerves represent the most common causes of tumor-related pain syn dromes.Pain relief from radiation therapy for bone metastases for lung, kidney, and colon cancers and melanoma occurs in 30 to 50 percent of cases, and our own studies of brachial and lumbosacral plexus tumor response to radiation therapy is 15 to 45 percent, depending on the tumor type.Epidemiologic studies reveal that one third of cancer patients undergoing active therapy have pain and that two thirds of patients with far advanced disease have pain.The percentages Dr. Hittle presents are im portant information, and I urge him to pub lish these data to provide for a full discus sion of the issue.
Medicinal Chemistry of Fluorinated Cyclic and Acyclic Nucleoside Phosphonates
Authors: Ondřej Baszczyňski, Zlatko Janeba
Journal: Medicinal Research Reviews (2013)

Abstract The fluorine atom plays an important role in medicinal chemistry because fluorine substitution has a strong impact on the physical, chemical, and biological properties of bioactive compounds. Such fluorine modifications have also been extensively studied among the pharmaceutically important class of nucleoside phosphonates, nucleotide analogues in which the phosphate group is replaced by the enzymatically and chemically stable phosphonate moiety. The fluorinated nucleoside phosphonates abound with antiviral, antiparasitic, and anticancer properties because they are able to act as inhibitors of important enzymes of nucleoside/nucleotide metabolism. In this paper, we review the biological properties of cyclic and acyclic nucleoside phosphonates modified by the attachment of one or more fluorine atoms to various parts of the molecule, namely to nucleobases, alkylphosphonate groups, cyclic or acyclic linkers, or to prodrug moieties.
Selective Persistence of Distinct Stem/B Leukaemic Stem Cells In Childhood Acute Lymphoblastic Leukaemia In Clinical Remission.
Authors: Christoph Lutz, Petter Woll, Anders Castor, Helen Ferry, Christina Jensen, Joanne Green, Helene Dreau, Michael Lutteropp, Anna Schuh, Georgina Hall, Chris Mitchell, Jan Zuna, Veronica Buckle, Sten Eirik W Jacobsen, Tariq Enver
Journal: Blood (2010)
Molecular monitoring of complete cytogenetic responders following treatment with imatinib (STI571, Gleevec) for CML: A report from the UKSTI571 study group.
Authors: Liang Feng, M. W. Drummond, J. Byrne, P. C. A. Shepherd, J. F. Apperley, S. G. O'Brien, C. F. Craddock, R. E. Clark, F. Cervantes, A. L. Lennard, T. L. Holyoake, R. M. Szydlo, J. M. Goldman, J. S. Kaeda
Journal: Blood (2002)