tbuckley/cabot-search huggingface dataset:
Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression
Authors: Marta F. Estrada, Sofia P. Rebelo, Emma J. Davies, Marta T. Pinto, Hugo Pereira, Vítor E. Santo, Matthew J. Smalley, Simon T. Barry, Emilio J. Gualda, Paula M. Alves, Elizabeth Anderson, Catarina Brito
Journal: Biomaterials (2015)

3D cell tumour models are generated mainly in non-scalable culture systems, using bioactive scaffolds. Many of these models fail to reflect the complex tumour microenvironment and do not allow long-term monitoring of tumour progression. To overcome these limitations, we have combined alginate microencapsulation with agitation-based culture systems, to recapitulate and monitor key aspects of the tumour microenvironment and disease progression. Aggregates of MCF-7 breast cancer cells were microencapsulated in alginate, either alone or in combination with human fibroblasts, then cultured for 15 days. In co-cultures, the fibroblasts arranged themselves around the tumour aggregates creating distinct epithelial and stromal compartments. The presence of fibroblasts resulted in secretion of pro-inflammatory cytokines and deposition of collagen in the stromal compartment. Tumour cells established cell-cell contacts and polarised around small lumina in the interior of the aggregates. Over the culture period, there was a reduction in oestrogen receptor and membranous E-cadherin alongside loss of cell polarity, increased collective cell migration and enhanced angiogenic potential in co-cultures. These phenotypic alterations, typical of advanced stages of cancer, were not observed in the mono-cultures of MCF-7 cells. The proposed model system constitutes a new tool to study tumour-stroma crosstalk, disease progression and drug resistance mechanisms.
Osteomyelitis
Authors: John L. Zeller
Journal: JAMA (2008)

Osteomyelitis Osteomyelitis is an inflammation of bone caused by an infecting organism.The infection may be limited to a single portion of the bone or may involve multiple areas.The infection is generally due to a single organism, but polymicrobial infections (caused by different and multiple bacteria or fungi) can occur, especially in patients with diabetes.Persons of any age can develop a bone infection, although it is more common in children and persons older than 50 years.The February 20, 2008, issue of JAMA includes an article about the difficulties of identifying and diagnosing osteomyelitis in patients with diabetes.
The Early Development of Wheeze. Environmental Determinants and Genetic Susceptibility at 17q21
Authors: Georg J. Loss, Martin Depner, Alexander J. Hose, Jon Genuneit, Anne M. Karvonen, Anne Hyvärinen, Caroline Roduit, Michael Kabesch, Roger Lauener, Petra Ina Pfefferle, Juha Pekkanen, Jean-Charles Dalphin, Josef Riedler, Charlotte Braun-Fahrländer, Erika von Mutius, Markus J. Ege
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Growing up on a farm protects from childhood asthma and early wheeze. Virus-triggered wheeze in infancy predicts asthma in individuals with a genetic asthma risk associated with chromosome 17q21.Objectives: To test environmental determinants of infections and wheeze in the first year of life, potential modifications of these associations by 17q21, and the implications for different trajectories of wheeze.Methods: We followed 983 children in rural areas of Europe from birth until age 6 years. Symptoms of wheeze, rhinitis, fever, and environmental exposures were documented with weekly diaries during year 1. Asthma at age 6 was defined as ever having a reported doctor’s diagnosis. Single-nucleotide polymorphisms related to ORMDL3 (rs8076131) and GSDMB (rs7216389, rs2290400) at 17q21 were genotyped.Measurements and Main Results: Early wheeze was positively associated with presence of older siblings among carriers of known asthma risk alleles at 17q21 (e.g., rs8076131) (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.16–2.01). Exposure to farm animal sheds was inversely related to wheeze (aOR, 0.44; 95% CI, 0.33–0.60). Both effects were similarly observed in children with transient wheeze up to age 3 years without subsequent development of asthma (aOR, 1.71 [95% CI, 1.09–2.67]; and aOR, 0.48 [95% CI, 0.30–0.76], respectively).Conclusions: These findings suggest that the chromosome 17q21 locus relates to episodes of acute airway obstruction common to both transient wheeze and asthma. The previously identified asthma risk alleles are the ones susceptible to environmental influences. Thus, this gene–environment interaction reveals two faces of 17q21: The same genotype constitutes genetic risk and allows for environmental protection, thereby providing options for prospective prevention strategies.
Association of Elevated Amyloid Levels With Cognition and Biomarkers in Cognitively Normal People From the Community
Authors: Ronald C. Petersen, Heather J. Wiste, Stephen D. Weigand, Walter A. Rocca, Rosebud O. Roberts, Michelle M. Mielke, Val J. Lowe, David S. Knopman, Vernon S. Pankratz, Mary M. Machulda, Yonas E. Geda, Clifford R. Jack
Journal: JAMA Neurology (2015)

The role of amyloid in the progression of Alzheimer disease (AD) pathophysiology is of central interest to the design of randomized clinical trials.The presence of amyloid has become a prerequisite for enrollment in several secondary prevention trials for AD, yet the precise effect of elevated amyloid levels on subsequent clinical and biomarker events is less certain.OBJECTIVE To explore the effect of elevated amyloid levels on subsequent changes in cognition and biomarkers. DESIGN, SETTING, AND PARTICIPANTSA total of 564 cognitively normal individuals (median age, 78 years) from the Mayo Clinic Study of Aging, a population-based longitudinal study in Olmsted County, Minnesota, with serial cognitive data were selected for this study.The data used in this study were collected from January 12, 2006, to January 9, 2014.Individuals included in this study had undergone magnetic resonance imaging, fluorodeoxyglucose positron emission tomography (FDG-PET), and Pittsburgh Compound B (PiB) PET at baseline were not cognitively impaired at baseline and had at least 1 clinical follow-up.A subset of 286 individuals also underwent serial imaging.Elevated amyloid level was defined as a standardized uptake value ratio of greater than 1.5 on PiB PET.Associations with baseline amyloid status and baseline and longitudinal change in clinical and imaging measures were evaluated after adjusting for age and hippocampal volume.APOE4 effects were also evaluated. MAIN OUTCOMES AND MEASURESCognitive measures of memory, language, attention/executive function, visuospatial skills, PiB levels, hippocampal and ventricular volumes, and FDG-PET measures.RESULTS At baseline, 179 (31.7%) individuals with elevated amyloid levels had poorer cognition in all domains measured, reduced hippocampal volume, and greater FDG-PET hypometabolism.Elevated amyloid levels at baseline were associated with a greater rate of cognitive decline in all domains (0.04 to 0.09 z score units per year) except language and a greater rate of amyloid accumulation (1.6% per year), hippocampal atrophy (30 mm 3 per year), and ventricular enlargement (565 mm 3 per year).Elevated amyloid levels were also associated with an increased risk of mild cognitive impairment (hazard ratio, 2.9; 95% CI, 1.7-5.0,and hazard ratio, 1.6; 95% CI, 0.9-2.8, for PiB+ APOE4 carriers and PiB+ noncarriers, respectively, compared with PiB-noncarriers).These associations were largely independent of APOE4. CONCLUSIONS AND RELEVANCEIn persons selected from a population-based study, elevated amyloid levels at baseline were associated with worse cognition and imaging biomarkers at baseline and with greater clinical decline and neurodegeneration.These results have implications for the design of randomized clinical trials for AD.
Phase II Trial of Up-Front Accelerated Thoracic Radiotherapy Combined With Chemotherapy and Optional Up-Front Prophylactic Cranial Irradiation in Limited Small-Cell Lung Cancer
Authors: A. Hügli, D. Moro, B. Mermillod, M. Bolla, P. Alberto, H. Bonnefoi, R. Miralbell
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To investigate the feasibility and outcome of bifractionated, up-front thoracic radiotherapy (TR) (45 Gy in 30 fractions of 1.5 Gy twice daily over 3 weeks) combined with chemotherapy (CT) (six cycles of cisplatin and etoposide) and optional low-dose, up-front prophylactic cranial irradiation (18 Gy in 10 fractions of 1.8 Gy twice daily over 5 days) in limited small-cell lung cancer. PATIENTS AND METHODS: CT (etoposide 100 mg/m 2 for 3 days and cisplatin 25 mg/m 2 for 3 days) was started on day 8 or 15 after the first TR treatment. In the five subsequent cycles, cisplatin was given as a single 100-mg/m 2 dose on day 1 every 4 weeks. A total of 52 patients were entered (41 men and 11 women); the median age was 55 years (range, 33 to 67 years). World Health Organization performance status was 0 in 34 patients, 1 in 16 patients, and 2 in two patients. Thirty-six patients (69%) received the full planned six cycles of CT. RESULTS: All treated patients were assessable for response. Thirty-one patients (60%) achieved a complete response, and 16 (30%) had a partial response. One-, 3-, and 4-year survival rates were 74% (95% confidence interval [CI], 60% to 84%), 34% (95% CI, 21% to 49%), and 32% (95 CI, 16% to 46%), respectively. The median survival time was 18 months. Event-free survival at 1 year was 45% (95% CI, 32% to 58%) and at 3 years, 30% (95% CI, 18% to 44%). The main radiation-related acute toxicity was esophageal: 38% of the patients experienced grade 3 or 4 acute toxicity. CT was well tolerated. Although grade 3/4 neutropenia was observed in 86% of the patients, only 4% presented with associated fever. Grade 3/4 nausea and vomiting was seen in 35% of patients. CONCLUSION: This trial demonstrates that up-front accelerated TR associated with CT is feasible, has acceptable toxicity, and shows considerable long-term survival potential.
Longitudinal analysis of the peripheral B cell repertoire reveals unique effects of immunization with a new influenza virus strain
Authors: Bernardo Cortina-Ceballos, Elizabeth Ernestina Godoy-Lozano, Juan Téllez-Sosa, Marbella Ovilla-Muñoz, Hugo Sámano-Sánchez, Andrés Aguilar-Salgado, Rosa Elena Gómez-Barreto, Humberto Valdovinos-Torres, Irma López-Martínez, Rodrigo Aparicio-Antonio, Mario H. Rodríguez, Jesús Martínez-Barnetche
Journal: Genome Medicine (2015)

Background: Despite the potential to produce antibodies that can neutralize different virus (heterotypic neutralization), there is no knowledge of why vaccination against influenza induces protection predominantly against the utilized viral strains (homotypic response).Identification of structural patterns of the B cell repertoire associated to heterotypic neutralization may contribute to identify relevant epitopes for a universal vaccine against influenza.Methods: Blood samples were collected from volunteers immunized with 2008/2009 trivalent inactivated vaccine (TIV), pandemic H1N1 (pdmH1N1) monovalent inactivated vaccine (MIV) and the 2014/2015 TIV.Neutralization was assessed by hemagglutination and microneutralization test.IgG V H amplicons derived from peripheral blood RNA from pre-immune and 7 days post vaccination were subjected to 454-Roche sequencing.Full reconstruction of the sampled repertoires was done with ImmunediveRsity.Results: The TIV induced a predominantly homotypic neutralizing serologic response, while the 09 MIV induced a heterotypic neutralizing seroconversion in 17 % of the individuals.Both the 08/09 and the 14/15 TIV were associated with a reduction in clonotypic diversity, whereas 09 MIV was the opposite.Moreover, TIV and MIV induced distinctive patterns of IGHV segment use that are consistent with B cell selection by conserved antigenic determinants shared by the pre-pandemic and the pandemic strains.However, low somatic hypermutation rates in IgG after 09 MIV immunization, but not after 08/09 and 14/15 TIV immunization were observed.Furthermore, no evidence of the original antigenic sin was found in the same individuals after vaccination with the three vaccines.Conclusions: Immunization with a new influenza virus strain (2009 pdmH1N1) induced unique effects in the peripheral B cell repertoire clonal structure, a stereotyped response involving distinctive IGHV segment use and low somatic hypermutation levels.These parameters were contrastingly different to those observed in response to pre-pandemic and post-pandemic vaccination, and may be the result of clonal selection of common antigenic determinants, as well as germinal center-independent responses that wane as the pandemic strain becomes seasonal.Our findings may contribute in the understanding of the structural and cellular basis required to develop a universal influenza vaccine.
Pulmonary Angiotensin-converting Enzyme (ACE) Binding and Inhibition in Humans
Authors: FENG QING, TIMOTHY J. McCARTHY, JOANNE MARKHAM, DANIEL P. SCHUSTER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Angiotensin-converting enzyme (ACE) inhibition attenuates pulmonary hypertension and delays the development of pulmonary vascular remodeling in animal models. Thus, ACE inhibition might be a useful treatment for primary pulmonary hypertension (PPH). To determine the dose of ACE inhibitor required to specifically block pulmonary ACE in humans, we measured the combined forward rate constant (CFRC) for [18F]-fluorocaptopril, which is proportional to the mass of ACE in the lung, using positron emission tomography (PET). In five normal subjects, CFRC was measured twice, 1 wk apart, to assess measurement reproducibility. The CFRC was 0.151 ± 0.067 for the first measurement and 0.140 ± 0.060 for the second measurement (p = not significant [NS]). In five normals, CFRC decreased on average 84%, from 0.177 ± 0.053/s to 0.028 ± 0.017/s (p < 0.05), after 1 wk ingestion of 5 mg enalapril orally once a day (the scans were performed 24 h after the last medication). Similarly, in five patients with PPH, CFRC decreased on average 76%, from 0.052 ± 0.020/s to 0.012 ± 0.003 (p < 0.01), after 1 wk enalapril, despite much lower baseline values. We conclude that the total mass of pulmonary ACE appears to be significantly reduced in PPH and that only low doses of ACE inhibitors may be needed to block the effects of ACE on vascular remodeling in PPH.
Hypertensive Diabetic Kidney as Model of So-Called Collagen Diseases
Authors: A C LENDRUM
Journal: JAMA (1963)

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
The National Health Service: past and future
Authors: Alan Langlands
Journal: Journal of the Royal Society of Medicine (1998)

Alan Langlands is the Chief Executive of the National Health Service in England and the most senior health service manager in the UK. He is the Secretary of State for Health's principal policy adviser for the NHS and is directly accountable to him for the effective stewardship of a revenue budget of £34bn. He joined the NHS in 1974 as a graduate trainee and has spent his working life in health care management. His experience includes time spent managing major teaching hospitals in London (the Middlesex and University College Hospitals and the Hospital for Women, Soho), running Harrow Health Authority; and developing a Health Care practice within Powers Perrin, an international management consultancy firm. From 1990–1992 he was the Regional General Manager of North West Thames Regional Health Authority; during 1993, he was seconded to the Department of Health as Deputy Chief Executive of the NHS where he was responsible for a major review of the top management of the NHS. Sir Alan is a science graduate of the University of Glasgow and holds the diploma of the Institute of Health Services Management. He is an Honorary Professor at the University of Warwick Business School and a board member of the Centre for Corporate Strategy and Change at the University. He is also an honorary fellow of the Faculty of Public Health Medicine of the Royal College of Physicians.
Primary acute myeloid leukemia cells with overexpression of EVI-1 are sensitive to all-trans retinoic acid
Authors: Han J. M. P. Verhagen, Marjon A. Smit, Arjo Rutten, Fedor Denkers, Pino J. Poddighe, Pauline A. Merle, Gert J. Ossenkoppele, Linda Smit
Journal: Blood (2015)
Determinants of Drug Disposition and Effect in the Fetus
Authors: T P Green, R F O'Dea, B L Mirkin
Journal: The Annual Review of Pharmacology and Toxicology (1979)

The disposition of pharmacologically active molecules in the maternal­ placental-fetal unit has been discussed in several recent books and reviews (1-3). Considerable data have accumulated to indicate that nearly all drugs enter the fetal circulation following maternal administration and may exert different effects upon the fetus. Hence, it is of considerable significance to determine the influence of biological maturation on placental transfer, the effects of drugs on placental function, fetal drug disposition, and the reac­ tivity of the fetus to pharmacologic agents. This review considers aspects of developmental pharmacology that have not been extensively considered in previous publications, examining in par­ ticular the following subject areas:
Phenotype, function and T cell receptor repertoire of tumor-infiltrating lymphocytes in patients with pancreatic ductal adenocarcinoma
Authors: Isabel Poschke, Michael Flossdorf, Marta Faryna, Frank Bergmann, Jessica Hassel, Oliver Strobel, Rienk Offringa
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median survival of only about two years even in the 20% of patients that present early enough to be eligible for surgical resection and adjuvant chemotherapy. With this urgent medical need in mind, we are
Autoregulation in adipose tissue: Pressure-flow measurements in inguinal fat pad on heparinized dogs during local hypotension, venous pressure elevation, and reactive hyperaemia
Authors: P. A. Nielsen, N. J. Secher
Journal: Cardiovascular Research (1971)

Journal Article Autoregulation in adipose tissue: Pressure-flow measurements in inguinal fat pad on heparinized dogs during local hypotension, venous pressure elevation, and reactive hyperaemia Get access P. Alstrup Nielsen, P. Alstrup Nielsen From the Institute of Physiology, University of Odense, and the Department of Thoracic Surgery and the Department of Clinical Physiology, University Hospital, Odense, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar N. J. Secher N. J. Secher From the Institute of Physiology, University of Odense, and the Department of Thoracic Surgery and the Department of Clinical Physiology, University Hospital, Odense, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 5, Issue 4, October 1971, Pages 572–576, https://doi.org/10.1093/cvr/5.4.572 Published: 01 October 1971
Ramipril versus placebo in kidney transplant patients with proteinuria: a multicentre, double-blind, randomised controlled trial
Authors: Greg A Knoll, Dean Fergusson, Michaël Chassé, Paul Hebert, George Wells, Lee Anne Tibbles, Darin Treleaven, David Holland, Christine White, Norman Muirhead, Marcelo Cantarovich, Michel Paquet, Bryce Kiberd, Sita Gourishankar, Jean Shapiro, Ramesh Prasad, Edward Cole, Helen Pilmore, Valerie Cronin, Debora Hogan, Tim Ramsay, John Gill
Journal: The Lancet Diabetes & Endocrinology (2015)
The LeVeen Shunt
Authors: H H LeVeen
Journal: Annual Review of Medicine (1985)

Ascites is the end result when the rate of conversion of plasma to peritoneal fluid exceeds the rate of reabsorption from the peritoneal cavity. Physiologic therapy demands the return of this fluid to the plasma volume from whence it arose. The peritoneovenous shunt was devised to accomplish this. If precautionary measures are followed, complications are avoided. The shunt can be accomplished with a mortality under 1% in uncomplicated cirrhosis without jaundice or hydrothorax. Postoperative coagulopathy and infection are avoidable complications. Shunt failure is partly preventable and can almost always be remedied. Patients must be carefully followed to prevent late sepsis: care must be even more rigorous than that given to implanted artificial heart valves, because of the lower resistance of cirrhotics to infection. The cause of death in ascites untreated by shunts is early renal failure that is averted by the shunt. The shunt does not prevent rupture of esophageal varices, a frequent mode of late mortality. Varices require separate therapy. Because the shunt is effective with minimal morbidity and mortality, the indications for a peritoneovenous shunt should be liberalized.
Factors determining myocardial oxygen consumption (MO2) during elevation of aortic blood pressure
Authors: O. D. MJØS, B. BUGGE-ASPERHEIM, F. KIIL
Journal: Cardiovascular Research (1972)

Journal Article Factors determining myocardial oxygen consumption (MO2) during elevation of aortic blood pressure: 2. Relation between MO2 and free fatty acids Get access O. D. MJØS, O. D. MJØS From the Institute for Experimental Medical Research, University of Oslo, Ullevaal Hospital, Oslo, Norway Search for other works by this author on: Oxford Academic PubMed Google Scholar B. BUGGE-ASPERHEIM, B. BUGGE-ASPERHEIM From the Institute for Experimental Medical Research, University of Oslo, Ullevaal Hospital, Oslo, Norway Search for other works by this author on: Oxford Academic PubMed Google Scholar F. KIIL F. KIIL From the Institute for Experimental Medical Research, University of Oslo, Ullevaal Hospital, Oslo, Norway Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 6, Issue 1, January 1972, Pages 23–27, https://doi.org/10.1093/cvr/6.1.23 Published: 01 January 1972