tbuckley/cabot-search huggingface dataset:
Northwick Park infection Consultation Service Part II. Contribution of the service to patient management: An analysis of results between September 1987 and July 1990
Authors: E.G.L. Wilkins, M.M. Hickey, S. Khoo, A.D. Hale, S. Umasankar, P. Thomas, N. Bhatti, J. Dave, D. Seal, E. Larson, R. Wall, Hillas Smith
Journal: Journal of Infection (1991)
Prognostic Impact of ΔTAp73 Isoform Levels and Their Target Genes in Colon Cancer Patients
Authors: Beatriz Soldevilla, Raquel Díaz, Javier Silva, Yolanda Campos-Martín, Concepción Muñoz, Vanesa García, José M García, Cristina Peña, Mercedes Herrera, Marta Rodriguez, Irene Gómez, Nagat Mohamed, Margarita M. Marques, Félix Bonilla, Gemma Domínguez
Journal: Clinical Cancer Research (2011)

Cumulative data support the role of ΔTAp73 variants in tumorigenic processes such as drug resistance. We evaluate the impact of TP73 isoforms and their putative target genes ABCB1, HMGB1, and CASP1 on the survival of colon cancer patients and the correlation between their expressions.We determined in 77 colon cancer patients the expression of ΔEx2p73, ΔEx2/3p73, ΔNp73, TAp73, ABCB1, HMGB1, and CASP1 by quantitative real-time reverse transcriptase-PCR. Tumor characteristics, disease-free survival, and overall survival (OS) were examined in each patient. Functional experiments were carried out to check whether ectopic expression of ΔNp73 modifies the proliferation, drug resistance, migration, and invasion properties of colon tumor cells and the expression of ABCB1, HMGB1, and CASP1.Positive correlations were observed between the expression levels of ΔTAp73 variants and HMGB1. Furthermore, a trend was observed for ABCB1. Overexpression of ΔEx2/3p73 and ΔNp73 isoforms was significantly associated with advanced stages (P = 0.04 and P = 0.03, respectively) and predicted shortened OS (P = 0.04 and P = 0.05, respectively). High levels of ABCB1 and HMGB1 were associated with shorter OS (P = 0.04 and P = 0.05, respectively). Multivariate analysis showed that, in addition to the tumor stage, ABCB1 and HMGB1 had independent relationships with OS (P = 0.008). Ectopic expression of ΔNp73 was associated with an increase in proliferation and drug resistance.The positive correlation between ΔTAp73 variants and HMGB1 and ABCB1 expression supports them as TP73 targets. The fact that upregulation of ΔTAp73 isoforms was associated with shortened OS, increase in proliferation, and drug resistance confirms their oncogenic role and plausible value as prognostic markers. ABCB1 and HMGB1, putative ΔTAp73 target genes, strongly predict OS in an independent manner, making clear the importance of studying downstream TP73 targets that could predict the outcome of colon cancer patients better than ΔTAp73 variants themselves do.
Can You Hear Me Now?
Authors: Rebecca Voelker
Journal: JAMA (2015)

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
Glue ear: the new dyslexia?
Authors: N Black
Journal: BMJ (1985)

Several factors have led to the current epidemic of surgery for glue ear in children, including the widespread introduction of audiometry; greater recognition of the presence of fluid in the middle ear by general practitioners; the availability of more otolaryngologists; and technical advances such as the availability of antibiotics to treat postoperative infections and of flanged tympanostomy tubes (grommets). The need of surgeons to fill the vacuum caused by the decline in the number of adenotonsillectomies, and the fact that a diagnosis of glue ear legitimises the continued use of these operations, may also have contributed to the increase. Finally, glue ear may provide parents with a medical explanation of their children's poor educational performance, as the term dyslexia did in the past. The high social and public costs of this operation demand a reappraisal of its increasing use.
Activator Protein-1 Activity Regulates Epithelial Tumor Cell Identity
Authors: Michael J. Gerdes, Maxim Myakishev, Nicholas A. Frost, Vikas Rishi, Jaideep Moitra, Asha Acharya, Michelle R. Levy, Sang-won Park, Adam Glick, Stuart H. Yuspa, Charles Vinson
Journal: Cancer Research (2006)

Abstract To examine the consequences of inhibiting activator protein-1 (AP-1) transcription factors in skin, transgenic mice were generated, which use the tetracycline system to conditionally express A-FOS, a dominant negative that inhibits AP-1 DNA binding. Older mice develop mild alopecia and hyperplasia of sebaceous glands, particularly around the eyes. When A-FOS was expressed during chemical-induced skin carcinogenesis, mice do not develop characteristic benign and malignant squamous lesions but instead develop benign sebaceous adenomas containing a signature mutation in the H-ras proto-oncogene. Inhibiting AP-1 activity after tumor formation caused squamous tumors to transdifferentiate into sebaceous tumors. Furthermore, reactivating AP-1 in sebaceous tumors results in a reciprocal transdifferentiation into squamous tumors. In both cases of transdifferentiation, individual cells express molecular markers for both cell types, indicating individual tumor cells have the capacity to express multiple lineages. Molecular characterization of cultured keratinocytes and tumor material indicates that AP-1 regulates the balance between the wnt/β-catenin and hedgehog signaling pathways that determine squamous and sebaceous lineages, respectively. Chromatin immunoprecipitation analysis indicates that c-Jun binds several wnt promoters, which are misregulated by A-FOS expression, suggesting that members of the wnt pathway can be a primary targets of AP-1 transcriptional regulation. Thus, AP-1 activity regulates tumor cell lineage and is essential to maintain the squamous tumor cell identity. (Cancer Res 2006; 66(15): 7578-88)
Rapid estimation of myocardial infarct size
Authors: A van der Laarse
Journal: Cardiovascular Research (1999)

See article by de Groot et al. [9] (pages 315–324) in this issue. 

Although the use of biochemical markers of acute myocardial infarction started in 1954 [1], their value in estimating myocardial infarct size was demonstrated roughly 20 years later. The groups of Hermens and colleagues [2] and Sobel and colleagues [3] independently reported methods to calculate infarct size on the basis of serial serum enzyme activities, such as creatine kinase (CK) and α-hydroxybutyrate dehydrogenase (αHBDH). The methods employed were based on the same principle: an input of marker ( e.g. an enzyme) from the infarcted myocardium into the circulation is calculated by correction of the enzyme's activity- vs -time curve for the output (clearance) of that marker from the circulation. To that purpose Sobel and colleagues used the late linear decline of CK's logarithmic activity- vs -time curve [3]. Hermens and colleagues stressed the fact that the use of slowly cleared enzymes, such as αHBDH, greatly diminished the influence of error in estimated clearance rates [4]. However, for slowly …
A tissue-specific transcriptional enhancer is found in the body of the HLA-DR alpha gene.
Authors: Y Wang, A S Larsen, B M Peterlin
Journal: The Journal of Experimental Medicine (1987)

We mapped cis-acting regulatory elements in the HLA-DR alpha gene, which encodes the monomorphic subunit of the HLA-DR heterodimer. Genomic fragments of HLA-DR alpha were placed 5' or 3' to the chloramphenicol acetyltransferase reporter gene, the transcription of which was initiated from the Herpes simplex thymidine kinase promoter. In transient expression assays, fragments from the body of the HLA-DR alpha gene were able to increase chloramphenicol acetyltransferase activity in a position-, orientation-, and promoter-independent yet tissue-specific fashion. These HLA-DR alpha cis-acting regulatory elements contain previously identified DNase I-hypersensitive sites and DNA sequences homologous to those found in other eukaryotic transcriptional enhancers.
In Utero Gene Therapy Rescues Vision in a Murine Model of Congenital Blindness
Authors: Nadine S Dejneka, Enrico M Surace, Tomas S Aleman, Artur V Cideciyan, Arkady Lyubarsky, Andrey Savchenko, T.Michael Redmond, Waixing Tang, Zhangyong Wei, Tonia S Rex, Ernest Glover, Albert M Maguire, Edward N Pugh, Samuel G Jacobson, Jean Bennett
Journal: Molecular Therapy (2004)

The congenital retinal blindness known as Leber congenital amaurosis (LCA) can be caused by mutations in the RPE65 gene. RPE65 plays a critical role in the visual cycle that produces the photosensitive pigment rhodopsin. Recent evidence from human studies of LCA indicates that earlier rather than later intervention may be more likely to restore vision. We determined the impact of in utero delivery of the human RPE65 cDNA to retinal pigment epithelium cells in a murine model of LCA, the Rpe65−/− mouse, using a serotype 2 adeno-associated virus packaged within an AAV1 capsid (AAV2/1). Delivery of AAV2/1-CMV-hRPE65 to fetuses (embryonic day 14) resulted in efficient transduction of retinal pigment epithelium, restoration of visual function, and measurable rhodopsin. The results demonstrate AAV-mediated correction of the deficit and suggest that in utero retinal gene delivery may be a useful approach for treating a variety of blinding congenital retinal diseases.
The German cystic fibrosis quality assurance project: clinical features in children and adults
Authors: B. Wiedemann, G. Steinkamp, B. Sens, M. Stern
Journal: European Respiratory Journal (2001)

Cystic fibrosis (CF) is a complex disease which requires interdisciplinary care in specialized CF centres. In Germany, 97 paediatric and adult outpatient clinics agreed to report clinical data of their patients to a newly established registry, the Cystic Fibrosis Quality Assurance (CFQA) project. This article characterizes the design of the CFQA and the health status of the patients enrolled by the end of 1997. Data from 4,306 patients reported to the CFQA project were analysed. Nutritional status and lung function of the patients were examined as well as the use of specific therapeutic interventions. Mean age of all 4,182 patients alive by the end of 1997 was 15.7 yrs (maximum, 58 yrs), and 35.8% of patients were &gt;18.0 yrs of age. One-third of the CF population were treated in the nine largest centres (each caring for &gt;100 patients). Abnormal nutritional status (weight-for-height &gt;90% of predicted or body mass index &lt;19.0 kg·m 2 , respectively) was observed in 26.8% of children and adolescents and in 38.3% of adults. Lung function was abnormal (forced expiratory volume in one second &lt;80% predicted) in the majority of adults (83.9%) and in 42.5% of the younger patients. The mortality rate was 1.4 of 100 patients in 1997. No clear association of clinical status with centre size was observed. The clinical features of patients treated in German cystic fibrosis centres were generally comparable to those reported from other countries, although improvements are certainly warranted. The Cystic Fibrosis Quality Assurance project represents an important tool for future progress in the quality of cystic fibrosis care.
Cardiovascular evaluation of middle-aged individuals engaged in high-intensity sport activities: implications for workload, yield and economic costs
Authors: Andrea Menafoglio, Marcello Di Valentino, Alessandra Pia Porretta, Pietro Foglia, Jeanne-Marie Segatto, Patrick Siragusa, Reto Pezzoli, Mattia Maggi, Gian Antonio Romano, Giorgio Moschovitis, Augusto Gallino
Journal: British Journal of Sports Medicine (2014)

Background The European Association of Cardiovascular Prevention and Rehabilitation (EACPR) recommends cardiovascular evaluation of middle-aged individuals engaged in sport activities. However, very few data exist concerning the impact of such position stand. We assessed the implications on workload, yield and economic costs of this preventive strategy. Methods Individuals aged 35–65 years engaged in high-intensity sports were examined following the EACPR protocol. Athletes with abnormal findings or considered at high-cardiovascular risk underwent additional examinations. The costs of the overall evaluation until diagnosis were calculated according to Swiss medical rates. Results 785 athletes (73% males, 46.8±7.3 years) were enrolled over a 13-month period. Among them, 14.3% required additional examinations: 5.1% because of abnormal ECG, 4.7% due to physical examination, 4.1% because of high-cardiovascular risk and 1.6% due to medical history. A new cardiovascular abnormality was established in 2.8% of athletes, severe hypercholesterolaemia in 1% and type 2 diabetes in 0.1%. Three (0.4%) athletes were considered ineligible for high-intensity sports, all of them discovered through an abnormal ECG. No athlete was diagnosed with significant coronary artery disease on the basis of a high-risk profile or an exercise ECG. The cost was US$199 per athlete and US$5052 per new finding. Conclusions Cardiovascular evaluation of middle-aged athletes detected a new cardiovascular abnormality in about 3% of participants and a high-cardiovascular risk profile in about 4%. Some of these warranted exclusion of the athlete from high-intensity sport. The overall evaluation seems to be feasible at reasonable costs.
BioCAST/IFCT-1002: epidemiological and molecular features of lung cancer in never-smokers
Authors: Sébastien Couraud, Pierre-Jean Souquet, Christophe Paris, Pascal Dô, Hélène Doubre, Eric Pichon, Adrien Dixmier, Isabelle Monnet, Bénédicte Etienne-Mastroianni, Michel Vincent, Jean Trédaniel, Marielle Perrichon, Pascal Foucher, Bruno Coudert, Denis Moro-Sibilot, Eric Dansin, Stéphanie Labonne, Pascale Missy, Franck Morin, Hélène Blanché, Gérard Zalcman
Journal: European Respiratory Journal (2015)

Lung cancer in never-smokers (LCINS) (fewer than 100 cigarettes in lifetime) is considered as a distinct entity and harbours an original molecular profile. However, the epidemiological and molecular features of LCINS in Europe remain poorly understood. All consecutive newly diagnosed LCINS patients were included in this prospective observational study by 75 participating centres during a 14-month period. Each patient completed a detailed questionnaire about risk factor exposure. Biomarker and pathological analyses were also collected. We report the main descriptive overall results with a focus on sex differences. 384 patients were included: 65 men and 319 women. 66% had been exposed to passive smoking (significantly higher among women). Definite exposure to main occupational carcinogens was significantly higher in men (35% versus 8% in women). A targetable molecular alteration was found in 73% of patients (without any significant sex difference): EGFR in 51%, ALK in 8%, KRAS in 6%, HER2 in 3%, BRAF in 3%, PI3KCA in less than 1%, and multiple in 2%. We present the largest and most comprehensive LCINS analysis in a European population. Physicians should track occupational exposure in men (35%), and a somatic molecular alteration in both sexes (73%).
Reducing the Trauma of Hospitalization
Authors: Allan S. Detsky, Harlan M. Krumholz
Journal: JAMA (2014)

US health policy analysts and payers are currently focused on the high rate of hospital readmission for patients who have been recently discharged. This issue is a particular concern for people older than 65 years and thus has become a focus of Medicare, which has implemented incentives to reduce 30-day readmission rates. Hospitals that fail to meet targets will be financially penalized.1 Acting on common sense, rather than evidence and a firm understanding of the causes of readmission, many suggest that rates could be reduced if hospitals only increased efforts to improve transitional care. Work began with greater attention to the cause of hospitalization and also on improved communication at the time of discharge and shortly thereafter.
Serum concentrations of two biochemical markers of brain tissue damage S-100B and neurone specific enolase are increased in elite female soccer players after a competitive game
Authors: B-M Stålnacke, A Ohlsson, Y Tegner, P Sojka
Journal: British Journal of Sports Medicine (2006)

Background: It is a matter of debate whether or not ordinary heading of the ball in soccer causes injury to brain tissue. Objective: To analyse concentrations of the biochemical markers of brain tissue damage S-100B and neurone specific enolase (NSE) in serum of female elite soccer players in association with a competitive game. Methods: Venous blood samples were obtained from 44 female soccer players before and after a competitive game for analysis. The number of headers and trauma events (falls, collisions, etc) was assessed from videotape recordings for each player. Results: Concentrations of both brain damage markers were increased after the game (S-100B, 0.18 (0.11) v 0.11 (0.05) μg/l (p = 0.000); NSE, 10.14 (1.74) v 9.05 (1.59) μg/l (p = 0.001)). There was a significant correlation between changes in S-100B concentrations and both the number of headers ( r = 0.430, p = 0.004) and the number of other trauma events ( r = 0.517, p&lt;0.001). Conclusion: The concentrations of both S-100B and NSE were increased by game associated activities and events. The increases in S-100B concentration were significantly related to the number of headers and other trauma events, which indicates that both these factors may have contributed to these increases.
Immunoproteomics of processed beef proteins reveal novel galactose‐α‐1,3‐galactose‐containing allergens
Authors: D. Apostolovic, T. A. T. Tran, C. Hamsten, M. Starkhammar, T. Cirkovic Velickovic, M. van Hage
Journal: Allergy (2014)

Abstract Background Red meat allergy presents a novel form of food allergy with severe delayed allergic reactions where IgE antibodies are directed against the carbohydrate α‐ G al epitope. Food preparation and processing can influence the allergenicity of proteins. The aim of this study was to characterize the proteomic profile of different beef preparations and to investigate their α‐Gal reactivity and potential allergenicity. Methods Extracts from raw, boiled, fried, and medium rare prepared beef were assessed by 2 D PAGE for the comparison of protein profiles. IgE‐binding proteins were identified using immunoblot‐coupled proteomic analysis using sera from red meat‐allergic patients. Presence of the α‐Gal epitope was verified using anti‐α‐Gal antibody and IgE inhibition immunoblot with α‐Gal. Results Multiple IgE‐binding proteins were detected in the different beef preparations, many of which were also recognized by the anti‐α‐Gal antibody. Protein spots reacting with IgE in patient sera were analyzed by MS / MS , resulting in identification of 18 proteins with high identification scores. Seven of the 18 beef allergens identified using meat‐allergic patient sera were also recognized by the anti‐α‐Gal monoclonal antibody, and four of them were stabile to thermal treatment. Furthermore, a dose‐dependent inhibition of red meat‐allergic patients’ IgE to beef by α‐Gal was demonstrated. Conclusions We show that the α‐Gal epitope is commonly present in IgE‐reactive beef proteins recognized by meat‐allergic patients. Seven novel α‐Gal‐containing IgE‐binding proteins were identified, of which four were stable to heat treatment. Thus, the allergenicity of red meat proteins is preserved even upon different thermal cooking.
Functional Restoration of BRCA2 Protein by Secondary<i>BRCA2</i>Mutations in<i>BRCA2</i>-Mutated Ovarian Carcinoma
Authors: Wataru Sakai, Elizabeth M. Swisher, Céline Jacquemont, Kurapaty Venkatapoorna Chandramohan, Fergus J. Couch, Simon P. Langdon, Kaitlyn Wurz, Jake Higgins, Emily Villegas, Toshiyasu Taniguchi
Journal: Cancer Research (2009)

Abstract Acquired platinum resistance is a serious problem in the treatment of ovarian carcinomas. However, the mechanism of the drug resistance has not been elucidated. Here, we show functional significance of restoration of BRCA2 protein by secondary BRCA2 mutations in acquired drug resistance of BRCA2-mutated ovarian carcinoma. Three ovarian cancer cell lines (PEO1, PEO4, and PEO6) were derived from a BRCA2 mutation [5193C&amp;gt;G (Y1655X)] carrier with ovarian carcinoma with acquired cisplatin resistance and a secondary BRCA2 mutation [5193C&amp;gt;T (Y1655Y)] that canceled the inherited mutation. PEO1 was BRCA2 deficient and sensitive to cisplatin and a poly(ADP-ribose) polymerase inhibitor, AG14361, whereas PEO4 was resistant. PEO4 and PEO6, derived from ascites at the time of relapse with cisplatin resistance, had the secondary mutation and were BRCA2 proficient. In vitro cisplatin/AG14361 selection of PEO1 led to restoration of BRCA2 due to another secondary BRCA2 mutation. BRCA2 depletion sensitized BRCA2-restored PEO1 clones and PEO4 to cisplatin/AG14361. Thus, restoration of BRCA2 due to secondary BRCA2 mutation is involved in acquired drug resistance of BRCA2-mutated ovarian carcinoma. [Cancer Res 2009;69(16):6381–6]