tbuckley/cabot-search huggingface dataset:
Targeting of Interferon-Beta to Produce a Specific, Multi-Mechanistic Oncolytic Vaccinia Virus
Authors: David H Kirn, Yaohe Wang, Fabrice Le Boeuf, John Bell, Steve H Thorne
Journal: PLoS Medicine (2007)

Background Oncolytic viruses hold much promise for clinical treatment of many cancers, but a lack of systemic delivery and insufficient tumor cell killing have limited their usefulness. We have previously demonstrated that vaccinia virus strains are capable of systemic delivery to tumors in mouse models, but infection of normal tissues remains an issue. We hypothesized that interferon-beta (IFN-β) expression from an oncolytic vaccinia strain incapable of responding to this cytokine would have dual benefits as a cancer therapeutic: increased anticancer effects and enhanced virus inactivation in normal tissues. We report the construction and preclinical testing of this virus. Methods and Findings In vitro screening of viral strains by cytotoxicity and replication assay was coupled to cellular characterization by phospho-flow cytometry in order to select a novel oncolytic vaccinia virus. This virus was then examined in vivo in mouse models by non-invasive imaging techniques. A vaccinia B18R deletion mutant was selected as the backbone for IFN-β expression, because the B18R gene product neutralizes secreted type-I IFNs. The oncolytic B18R deletion mutant demonstrated IFN-dependent cancer selectivity and efficacy in vitro, and tumor targeting and efficacy in mouse models in vivo. Both tumor cells and tumor-associated vascular endothelial cells were targeted. Complete tumor responses in preclinical models were accompanied by immune-mediated protection against tumor rechallenge. Cancer selectivity was also demonstrated in primary human tumor explant tissues and adjacent normal tissues. The IFN-β gene was then cloned into the thymidine kinase (TK) region of this virus to create JX-795 (TK−/B18R−/IFN-β+). JX-795 had superior tumor selectivity and systemic intravenous efficacy when compared with the TK−/B18R− control or wild-type vaccinia in preclinical models. Conclusions By combining IFN-dependent cancer selectivity with IFN-β expression to optimize both anticancer effects and normal tissue antiviral effects, we were able to achieve, to our knowledge for the first time, tumor-specific replication, IFN-β gene expression, and efficacy following systemic delivery in preclinical models.
Presymptomatic Diagnosis of Delayed-Onset Disease With Linked DNA Markers
Authors: Jason Brandt
Journal: JAMA (1989)

Clinical medicine in the 21st century is almost certain to include wide-scale use of molecular genetic diagnostic tests. In September 1986, The Johns Hopkins University School of Medicine initiated a voluntary program of presymptomatic genetic testing for Huntington's disease for persons at 50% risk. DNA analyses using the D4S10 (G8), D4S43, and D4S95 locus probes have been performed for 55 people. Twelve of the tests have yielded positive results, 30 were negative, and 13 were uninformative. Initial reactions ranged from joy and relief to disappointment, sadness, and demoralization. Thus far, there have been no severe depressive reactions. Although the sample size is small, our data suggest that people who receive genetic test results cope well, at least over the short term, when the testing is performed in a clinical context that includes education, pretest counseling, psychological support, and regular follow-up. (<i>JAMA</i>. 1989;261:3108-3114)
PWE-116 Can the new ESPGHAN diagnostic guidelines for coeliac disease be applied to adults?
Authors: L L Wong, R Sood, G Robins
Journal: Gut (2012)

<h3>Introduction</h3> In adults, duodenal biopsy is mandatory for diagnosis of coeliac disease. This is usually preceded by serological tests for coeliac specific antibodies—anti-tissue transglutaminase (tTG) and endomysial antibodies (EMA). However, the recent guidelines produced by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)<sup>1</sup> in 2010 recommend that histological assessment (duodenal biopsy) might be omitted in cases of anti-tTG more than 10 times the upper limit of normal which have been verified by endomysial positivity, a typical history for coeliac disease and HLA DQ2 or DQ8 positivity. Our aim was to analyse our adult population of patients with possible diagnosis of coeliac disease to ascertain the proportion of patients with anti-tTG levels more than 10 times the upper limit of normal. <h3>Methods</h3> Retrospective collection of data were obtained from the electronic clinical patient database from 2008 to 2011 at York Hospital. Inclusion criteria were all patients with positive anti-tTG and available duodenal histology results while on normal diet. York Hospital uses the Orgentec Anti-tTG IgA kit. <h3>Results</h3> 113 (70%) of the 161 patients were female. The median age was 49 years (Range 16–89 years). 52 patients (32%) had anti-tTG levels greater than 10 times the upper limit of normal (ie, with a value ≥100 u/ml). All 52 had positive EMA. 51/52 had typical symptoms (chronic diarrhoea, weight loss, fatigue, anaemia) while one patient had leg weakness and a positive family history for coeliac disease. All 52 patients had biopsies consistent with coeliac disease. One patient had HLA DQ2/DQ8 status checked, which was positive. The test was done due to equivocal IgA levels, weakly positive anti-tTG and Marsh I findings. <h3>Conclusion</h3> In our local adult population of patients with known positive anti-tTG and duodenal histology, about a third of the patients had anti-tTG levels greater than 10 times the upper limit of normal. This group had biopsies consistent with coeliac disease. Therefore, the ESPGHAN diagnostic guideline recommending the omission of duodenal biopsies in patients with anti-tTG levels greater than 10 times the upper limit of normal may be applicable for a significant proportion of the adult population (other similar studies<sup>2 3</sup> have found rates of 45–58%). <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <i>ESPGHAN Guidelines Diagnosis Coeliac Disease Children/Adolescents</i>. 2010. http://www.celiac-disease-consortium.nl/attachments/080_Mearin%20ESPGHAN%20CD%20WG%20voor%20CDC%20november%202010.pdf 2. <b>Mubarak A</b>, Wolters VM, Gerritsen SA, <i>et al.</i> A biopsy is not always necessary to diagnose celiac disease. J Pediatr Gastroenterol Nutr 2011;<b>52</b>:554–7. 3. <b>Hill PG</b>, Holmes GK. Coeliac disease: a biopsy is not always necessary for diagnosis. <i>Aliment Pharmaco Ther</i> 2008; <b>27</b>:572–7.
The role of glucose transporters in the distribution of p-aminophenyl-α-d-mannopyranoside modified liposomes within mice brain
Authors: Dan Du, Naidan Chang, Shouli Sun, Minghui Li, Hui Yu, Meifang Liu, Xiaoying Liu, Guangtian Wang, Haichun Li, Xunpei Liu, Shilong Geng, Qun Wang, Haisheng Peng
Journal: Journal of Controlled Release (2014)
TCT-900 High-degree Atrioventricular Block and Need for Permanent Pacemaker Implantation after Transcatheter and Surgical Aortic Valve Replacement
Authors: Irene Franzoni, Azeem Latib, Marco Mussardo, Massimo Slavich, Francesco Sacco, Andrea Radinovic, Ahmed Rezq, Filippo Figini, Alaide Chieffo, Matteo Montorfano, Gill Louise Buchanan, Letizia Bertoldi, Chiara Bernelli, Sandeep Basavarajaiah, Tasuku Hasegawa, Francesco Maisano, Antonio Colombo
Journal: Journal of the American College of Cardiology (2012)
Physical Activity in Women
Authors: I-Min Lee
Journal: JAMA (2003)

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
SC-23 * THE ROLE OF SINGLE AMINO ACID POLYMORPHISMS IN GLIOMA STEM CELL PHENOTYPES
Authors: C. L. Nilsson, A. Vegvari, E. Mostovenko, C. F. Lichti, D. Fenyo, K. Ruggles, E. P. Sulman
Journal: Neuro-Oncology (2014)

Recurrence of primary GBM is nearly inevitable and recurrent tumors are often more aggressive than the primary tumor. State-of-the-art sequencing and analysis methods have been applied to many tumor types, including GBM. While a large number of studies of genetic mutations and proteomic expression in GBM have been published, none have comprehensively examined the gene and protein expression of protein variants. This is due, in part, to the challenge in obtaining fresh material from patient specimens to study. Our panel of glioma stem cell lines (GSCs) have undergone comprehensive, quantitative analysis of their gene activity and proteomes. Proteins that normally have cell-protective properties, but harbor amino acid substitutions induced by single nucleotide polymorphisms (nsSNPs), may be transformed into proteins that promote genetic instability, dysregulate epigenetic control, and increase tumor invasivity. Those protein variants are not detected with conventional proteomic methods. To understand the role of protein-level expressed nsSNPs, which lead to single amino acid polymorphisms (SAAPs), in tumor invasivity and the resistance of GSCs to standard-of-care treatments, we established a novel, orthogonal bioinformatic approach to identify expressed protein SAAPs, a targeted proteomic analytical platform that enables the quantitation of SAAPs, and a phosphoproteomic approach to decipher GSC responses to pharmacological treatments. Using our novel analytical tools to study GSCs, we have already defined a set of eighteen protein SAAPs expressed in one or more cell lines that are implicated in the functional categories of DNA repair, transcriptional regulator, or protein kinase. We correlated the expression of protein variants with GSC phenotype, and defined patterns in intracellular signaling in GSCs in response to temozolomide (TMZ) and radiation treatments. The underlying molecular patterns are expected to help define the inadequate responses of GSCs to TMZ and radiation.
Transdiagnostic Factors and Mediation of the Relationship Between Perceived Racial Discrimination and Mental Disorders
Authors: Craig Rodriguez-Seijas, Malki Stohl, Deborah S. Hasin, Nicholas R. Eaton
Journal: JAMA Psychiatry (2015)

Multivariable comorbidity research indicates that many common mental disorders are manifestations of 2 latent transdiagnostic factors, internalizing and externalizing. Environmental stressors are known to increase the risk for experiencing particular mental disorders, but their relationships with transdiagnostic disorder constructs are unknown. The present study investigated one such stressor, perceived racial discrimination, which is robustly associated with a variety of mental disorders.To examine the direct and indirect associations between perceived racial discrimination and common forms of psychopathology.Quantitative analysis of 12 common diagnoses that were previously assessed in a nationally representative sample (N = 5191) of African American and Afro-Caribbean adults in the United States, taken from the National Survey of American Life, and used to test the possibility that transdiagnostic factors mediate the effects of discrimination on disorders. The data were obtained from February 2001 to March 2003. Latent variable measurement models, including factor analysis, and indirect effect models were used in the study.Mental health diagnoses from reliable and valid structured interviews and perceived race-based discrimination.While perceived discrimination was positively associated with all examined forms of psychopathology and substance use disorders, latent variable indirect effects modeling revealed that almost all of these associations were significantly mediated by the transdiagnostic factors. For social anxiety disorder and attention-deficit/hyperactivity disorder, complete mediation was found.The pathways linking perceived discrimination to psychiatric disorders were not direct but indirect (via transdiagnostic factors). Therefore, perceived discrimination may be associated with risk for myriad psychiatric disorders due to its association with transdiagnostic factors.
Antimetastatic Effects of Blocking PD-1 and the Adenosine A2A Receptor
Authors: Deepak Mittal, Arabella Young, Kimberley Stannard, Michelle Yong, Michele W.L. Teng, Bertrand Allard, John Stagg, Mark J. Smyth
Journal: Cancer Research (2014)

Adenosine targeting is an attractive new approach to cancer treatment, but no clinical study has yet examined adenosine inhibition in oncology despite the safe clinical profile of adenosine A2A receptor inhibitors (A2ARi) in Parkinson disease. Metastasis is the main cause of cancer-related deaths worldwide, and therefore we have studied experimental and spontaneous mouse models of melanoma and breast cancer metastasis to demonstrate the efficacy and mechanism of a combination of A2ARi in combination with anti-PD-1 monoclonal antibody (mAb). This combination significantly reduces metastatic burden and prolongs the life of mice compared with either monotherapy alone. Importantly, the combination was only effective when the tumor expressed high levels of CD73, suggesting a tumor biomarker that at a minimum could be used to stratify patients that might receive this combination. The mechanism of the combination therapy was critically dependent on NK cells and IFNγ, and to a lesser extent, CD8(+) T cells and the effector molecule, perforin. Overall, these results provide a strong rationale to use A2ARi with anti-PD-1 mAb for the treatment of minimal residual and metastatic disease.
Chitosan tubes of varying degrees of acetylation for bridging peripheral nerve defects
Authors: Kirsten Haastert-Talini, Stefano Geuna, Lars B. Dahlin, Cora Meyer, Lena Stenberg, Thomas Freier, Claudia Heimann, Christina Barwig, Luis F.V. Pinto, Stefania Raimondo, Giovanna Gambarotta, Silvina Ribeiro Samy, Nuno Sousa, Antonio J. Salgado, Andreas Ratzka, Sandra Wrobel, Claudia Grothe
Journal: Biomaterials (2013)

Biosynthetic nerve grafts are desired as alternative to autologous nerve grafts in peripheral nerve reconstruction.Artificial nerve conduits still have their limitations and are not widely accepted in the clinical setting.Here we report an analysis of fine-tuned chitosan tubes used to reconstruct 10 mm nerve defects in the adult rat.The chitosan tubes displayed low, medium and high degrees of acetylation (DAI: w2%, DA: w5%, DAIII: w20%) and therefore different degradability and microenvironments for the regenerating nerve tissue.Short and long term investigations were performed demonstrating that the chitosan tubes allowed functional and morphological nerve regeneration similar to autologous nerve grafts.Irrespective of the DA growth factor regulation demonstrated to be the same as in controls.Analyses of stereological parameters as well as the immunological tissue response at the implantation site and in the regenerated nerves, revealed that DAI and DAIII chitosan tubes displayed some limitations in the support of axonal regeneration and a high speed of degradation accompanied with low mechanical stability, respectively.The chitosan tubes combine several pre-requisites for a clinical acceptance and DAII chitosan tubes have to be judged as the most supportive for peripheral nerve regeneration.
The hazards of good memory
Authors: Mukaila Raji
Journal: BMJ (2005)

Forgetting is bad. Remembering is always good. Or so I thought until I met patients with unexpected benefits of memory loss. “It will be a blessing if I lose my mind,” one patient said. “I'll probably be happy not knowing I owe anybody!” Andy Rooney wrote, in his 1982 book, And More by Andy Rooney , “Sadness is one of the principal ingredients of memory, and there's just so much of that [that] anyone wants to bring on himself on purpose by sitting around remembering.” All this raises an important question in my mind. Is forgetfulness nature's way of enforcing forgiveness, the letting go of past wrongs and sorrows, the memory of which can only sadden the ageing mind, with little chance for reconciliation and closure?

In pondering this question I wonder whether the evolutionary reason for the high prevalence of Alzheimer's disease among those aged 80 or …
Is somatostatin a humoral regulator of the endocrine pancreas and gastric acid secretion in man?
Authors: F B Loud, J J Holst, E Egense, B Petersen, J Christiansen
Journal: Gut (1985)

The effect of low dose infusions of somatostatin on meal stimulated gastric acid secretion was studied in eight healthy volunteers by intragastric titration after a peptone test meal with radioimmunoassay control of the plasma concentrations of somatostatin and the pancreatic hormones glucagon and insulin. Infusion of somatostatin in a dose of 100 ng/kg/h, resulting in a plasma concentration of 13.4 +/- 2.1 pmol/l, inhibited acid secretion significantly, and in a dose of 800 ng/kg/h, with corresponding plasma concentration of 66.5 +/- 12.0 pmol/l the acid secretion was virtually abolished. Plasma concentrations of insulin and pancreatic glucagon decreased significantly during infusion of 200 ng/kg/h (24.5 +/- 7.5 pmol/l) and glucose concentrations increased. Serum gastrin was only significantly decreased during the highest dose of somatostatin. The range of plasma somatostatin concentrations obtained with the lower doses correspond to reported physiological variations. The results support the concept that somatostatin participates in the hormonal control of the pancreatic endocrine and the acid secretion.
Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen.
Authors: R T Matheson, D R Miller, M J Lacombe, Y N Han, S Iwanaga, H Kato, K D wuepper
Journal: Journal of Clinical Investigation (1976)

Flaujeac trait is the functional deficiency of a plasma protein of the intrinsic coagulation, kinin-forming, and plasma fibrinolytic pathways. The Flaujeac factor in man has been isolated and tentatively identified as a kininogen of high molecular weight (HMW). Highly purified bovine HMW-kininogen, but not bovine low molecular weight kininogen, repaired Flaujeac factor deficiency. The two subspecies of this molecule, HMW-kininogen a and HMW-kininogen b, also corrected Flaujeac factor deficiency. When bovine HMW-kininogen was incubated with bovine plasma kallikrein, kinin-free HMW-kininogen, bradykinin, and a glycopeptide fragment (peptide 1-2; 12,584 daltons) were rapidly released. None of these fragmentation products corrected Flaujeac factor deficiency alone or in mixtures. The function of HMW-kininogen appeared to depend upon the structural integrity of the native molecule. When injected in concentrations of 2 pmol-8 nmol/0.1 ml, peptide 1-2 caused increased vascular permeability in rabbits, rats, or guinea pigs. The enhanced permeability was maximal within 1-2 min and terminated in 5-10 min, differing from that of bradykinin or histamine. Injected together in equimolar amounts, peptide 1-2 and bradykinin produced a synergistic permeability response which was immediate in onset as well as prolonged in duration. Peptide 1-2 is a rapidly acting, highly basic glyco-peptide which mediates increased vascular permeability in a complementary and synergistic manner with bradykinin.
ED-30 * MULTI-CENTER RETROSPECTIVE COHORT STUDY OF ADULT INTRACRANIAL EPENDYMOMA: BRAIN TUMOR REGISTRY OF JAPAN 2001-2004
Authors: S. Tanaka, A. Mukasa, Y. Uematsu, J. Fukai, N. Saito
Journal: Neuro-Oncology (2014)

OBJECTIVE: Intracranial ependymoma is a rare brain tumor in adults. The standard treatments comprise of aggressive resection and radiotherapy, although only a few contemporary studies have evaluated their prognostic values. The objective of this study is to analyze clinical data from Brain Tumor Registry of Japan for assessing prognostic factors in adult intracranial ependymoma. MATERIALS AND METHODS: Seventy-six adult patients of intracranial ependymoma treated at 31 hospitals between 2001 and 2004 were included in the study. Subependymoma was excluded. Clinical data collected prospectively were retrospectively analyzed. RESULTS: The median age was 45 years (range,18-85), and the median KPS score was 80 (range,40-90). Infratentorial and multiple tumors were noted in 40 and 4 cases, respectively. Forty-five cases were classified as WHO grade 2 and 29 cases as grade 3. Grade 3 tumors were significantly associated with low KPS score, supratentorial tumor, large tumor diameter, and seizure onset compared to grade 2 tumors. All the grade 3 tumors except one were treated with radiotherapy and/or chemotherapy, while only 18 were treated with radiotherapy among 45 grade 2 tumors. With a median follow-up of 40 months, 5-year overall survival (OS) was 98% for grade 2 and 46% for grade 3; the median OS was not reached for grade 2 and 44 months for grade 3. Five-year progression-free survival (PFS) was 85% for grade 2 and 33% for grade 3; the median PFS was not reached for grade 2 and 21 months for grade 3. Multivariate analyses revealed that WHO grade (P = 0.009), complete resection (P = 0.002), and KPS score (P = 0.02) were associated with OS and that WHO grade (P = 0.02) and complete resection (P = 0.003) with PFS. CONCLUSION: WHO grade 3 ependymoma more often presents as a supratentorial mass provoking seizure than grade 2. WHO grade and complete resection were independent prognostic factors in adult intracranial ependymoma.