tbuckley/cabot-search huggingface dataset:
Misconduct is a behaviour, not a state
Authors: A. J. Ashworth
Journal: BMJ (2010)

<h3>Background</h3> Immunotherapy of cancer is successful but tumor regression often is incomplete and followed by escape. Understanding the mechanisms underlying this acquired resistance will aid the development of more effective treatments. <h3>Methods</h3> We exploited a mouse model where tumor-specific therapeutic vaccination results in tumor regression, followed by local recurrence and resistance. In depth studies on systemic, local and tumor intrinsic changes were performed with flow and mass cytometry, immunohistochemistry, transcriptomics and several perturbation studies with inhibitors or agonistic antibodies in mice. Main findings were recapitulated in vaccinated patients. <h3>Results</h3> Full tumor regression and cure of tumor-bearing mice is dependent on the magnitude of the vaccine-induced T-cell response. Recurrence of tumors did not involve classical immune escape mechanisms, such as antigen-presentation alterations, immune checkpoint expression, resistance to killing or local immune suppression. However, the recurrent tumors displayed a changed transcriptome with alterations in p53, tumor necrosis factor-α and transforming growth factor-β signaling pathways and they became immunologically cold. Remarkably, ex vivo cell-sorted recurrent tumors, directly reinjected in naïve hosts retained their resistance to vaccination despite a strong infiltration with tumor-specific CD8<sup>+</sup> T cells, similar to that of vaccine-responsive tumors. The influx of inflammatory mature myeloid effector cells in the resistant tumors, however, was impaired and this turned out to be the underlying mechanisms as restoration of inflammatory myeloid cell infiltration reinstated the sensitivity of these refractory tumors to vaccination. Notably, impaired myeloid cell infiltration after vaccination was also associated with vaccine resistance in patients. <h3>Conclusion</h3> An immunotherapy-induced disability of tumor cells to attract innate myeloid effector cells formed a major mechanism underlying immune escape and acquired resistance. These data not only stresses the importance of myeloid effector cells during immunotherapy but also demands for new studies to harness their tumoricidal activities.
COULD RETINAL IMAGING PROVIDE A SIMPLE INEXPENSIVE NONINVASIVE INDEX FOR CORONARY MICROVASCULAR FUNCTION IN WOMEN WITH CHEST PAIN AND NONOBSTRUCTIVE CORONARY ARTERY DISEASE? AN ANCILLARY PILOT STUDY FROM THE NHLBI-SPONSORED WOMEN'S ISCHEMIA SYNDROME EVALUATION (WISE-ARIC)
Authors: Eileen M. Handberg, Xuerong Wen, Ronald Klein, R. David Anderson, Daniel F. Pauly, Sheryl F. Kelsey, C. Noel Bairey Merz, George Sopko, Anil Puri, Lola Xie, Carl J. Pepine
Journal: Journal of the American College of Cardiology (2011)
The physician's obligation to his patients
Authors: A. P. Peeke
Journal: JAMA (1968)

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
Characterization of a bovine collagen–hydroxyapatite composite scaffold for bone tissue engineering
Authors: C.V.M. Rodrigues, P. Serricella, A.B.R. Linhares, R.M. Guerdes, R. Borojevic, M.A. Rossi, M.E.L. Duarte, M. Farina
Journal: Biomaterials (2003)
Evaluation of validity of British anthropometric reference data for assessing nutritional state of elderly people in Edinburgh: cross sectional study
Authors: E. Bannerman, J J Reilly, W J MacLennan, T Kirk, F Pender
Journal: BMJ (1997)

To evaluate the appropriateness of two sets of commonly used anthropometric reference data for nutritional assessment of elderly people.Cross sectional study.Two general practices in Edinburgh.200 independently living men and women aged 75 or over randomly recruited from the age and sex register of the practices.Weight (kg), knee height (cm), demispan (cm), mid-upper arm circumference (cm), triceps skinfold thickness (mm), arm muscle circumference (cm) body mass index (kg/m2), and demiquet (kg/m2) in men and mindex (kg/m) in women.Men and women in Edinburgh were significantly shorter than those in measured for the Nottingham reference data (demispan 0.79 v 0.80 (P < 0.05) for men and 0.72 v 0.73 (P < 0.01) for women). Comparison with data from South Wales showed that men and women from Edinburgh had significantly greater mid-upper arm circumference, triceps skinfold thickness, and arm muscle circumference. No one fell below the 10th centile of the South Wales data (the commonly used out off point for determining malnutrition) for these measures.Both sets of reference data commonly used in Britain may be inappropriate for nutritional screening of elderly people in Edinburgh. Contemporary reference data appropriate for the whole of Britain need to be developed, and in the longer term biologically or clinically defined criteria for undernutrition should be established.
Slow walking speed in elderly people
Authors: R. H Harwood, S. P Conroy
Journal: BMJ (2009)

Is associated with vascular mortality, but may also predict future frailty 

People who walk faster are less likely to die than slow walkers, especially from vascular disease. In the linked prospective cohort study (doi:10.1136/bmj.b4460), Dumurgier and colleagues show that this is true for walking speed measured over 6 m in 3208 relatively fit older people, over five years of follow-up.1

Walking speed is determined by physical features such as age, sex, and height, by the presence or absence of diseases, and by physical fitness.

Evidence that exercise is beneficial for health goes back over 50 years, and includes activity during sport and work as well as fitness training. Benefits are primarily in mortality and morbidity from vascular disease, and are seen in middle aged and older people, and those with and without established cardiovascular disease, diabetes, hypertension, or obesity.2 3

Diseases that slow down walking include musculoskeletal, cardiac, respiratory, neurological, and psychiatric disorders. Some of these are associated with excess mortality from vascular disease by virtue of being vascular …
The Dueling Diagnoses of Darwin
Authors: Ralph Colp
Journal: JAMA (1997)

To the Editor.  —While I agree with Drs Barloon and Noyes 1 that Charles Darwin had an illness that may be diagnosed as  disorder, I should like to make 3 comments about this diagnosis. First, as I have shown, Darwin had episodes of facial eczema that appear to have been psychosomatic in origin and that often were caused by controversies over his revolutionary ideas. 2 As far as I can determine, skin afflictions are not among the many somatic complaints that comprise panic disorder.  Second, it is possible that Darwin's many gastrointestinal symptoms were the result of Chagas disease, which he contracted by him during the Beagle voyage. This disorder was first active and then became inactive, permanently injuring the parasympathetic nerves of his stomach and making it more sensitive to sympathetic stimulation and hence more sensitive to the psychosomatic impact of his anxieties. 3 An organic impairment best explains the lifelong
Hypertension, Adrenal Abnormalities, and Alterations in Plasma Renin Activity
Authors: J. CAULlE GUNNELLS
Journal: Annals of Internal Medicine (1970)

Serial measurements of peripheral venous plasma renin activity were done in a group of patients with benign hypertension. Preoperative evidence of subnormal or suppressed plasma renin activity in response to a standardized protocol was demonstrated in 32 patients. Hypokalemia was present in 21 patients, and the other 11 patients had normal or variable concentrations of serum potassium. Urinary aldosterone excretion rates were increased in 19 patients and were normal or borderline-elevated in 13 patients. Adrenal exploration showed structural adrenal abnormalities in 90% of these 32 patients. After an average postoperative follow-up of 30 months, 23 patients (79%) had a satisfactory reduction in blood pressure; 6 patients remained hypertensive, and 3 patients who were followed less than 3 months were not included in the follow-up results. The diagnostic value and possible therapeutic indication of suppressed or subnormal plasma renin activity in the detection of adrenal abnormalities coexistent with benign hypertension are reviewed.
D-Bulboventricular Loop with L-Transposition in Situs Inversus
Authors: R. H. ANDERSON, R. ARNOLD, R. S. JONES
Journal: Circulation (1972)

In the case described anatomically corrected transposition of the great vessels is associated with situs inversus. Anatomically corrected transposition is extremely rare, and has not been previously reported with situs inversus. This type of transposition should not be confused with classical corrected transposition. Thus the case examined exhibited a D-bulboventricular loop with L-transposition and atrial inversion, so that blood flow was physiologically incorrect as in classical complete transposition. In the case examined, it was also found that bulbar musculature was present between the aorta and the mitral valve. Additional study of the conducting tissue revealed inversion of the sinoatrial node with the atria, and also of the atrial portion of the atrioventricular node. The atrioventricular bundle and its branches were in expected positions in relation to a large ventricular septal defect. These results are discussed with regard to previous reports and to the embryology of the conducting tissue.
Vascular Effects of the Human Extracellular Superoxide Dismutase R213G Variant
Authors: Yi Chu, Abdullah Alwahdani, Shinichiro Iida, Donald D. Lund, Frank M. Faraci, Donald D. Heistad
Journal: Circulation (2005)

Background— Extracellular superoxide dismutase (ECSOD) is a major extracellular antioxidant enzyme. We have demonstrated that vascular effects of ECSOD require an intact heparin-binding domain. A common genetic variant with a substitution in the heparin-binding domain (ECSOD R213G ) was reported recently to be associated with ischemic heart disease. The goal of this study was to examine vascular effects of ECSOD R213G . Methods and Results— A recombinant adenovirus (Ad) that expresses ECSOD R213G was constructed. ECSOD R213G and ECSOD proteins bound to collagen type I in vitro, but binding to aorta ex vivo was 10-fold greater with ECSOD than ECSOD R213G . Three days after intravenous injection of AdECSOD R213G or AdECSOD in spontaneously hypertensive rats (SHR), immunostaining demonstrated binding of ECSOD to carotid arteries and kidneys but minimal binding of ECSOD R213G . Binding to aorta and carotid artery was 2.5- to 3-fold greater with ECSOD than ECSOD R213G by immunoblotting. Arterial pressure was significantly reduced by AdECSOD but not by AdECSOD R213G . Responses to acetylcholine and basal levels of nitric oxide in carotid arteries were impaired in SHR compared with normotensive Wistar-Kyoto rats and were improved after AdECSOD but not AdECSOD R213G . Levels of superoxide and nitrotyrosine in aorta were higher in SHR than Wistar-Kyoto rats and were greatly reduced after AdECSOD but not AdECSOD R213G . Conclusions— In contrast to ECSOD, ECSOD R213G has no significant protective effect on arterial pressure, vascular function, or vascular levels of oxidative stress in SHR. These findings may provide a mechanistic basis for association studies that suggest that human beings carrying ECSOD R213G are predisposed to vascular diseases.
678. Inflammatory Cytokines Regulate Transgene Expression from Rheumatoid Synoviocytes Infected with Double Stranded Adeno-Associated Virus Vectors
Authors: Russell S. Traister, Sylvie Fabre, Xiao Xiao, Raphael Hirsch
Journal: Molecular Therapy (2005)

A major drawback to current gene transfer strategies is the inability to regulate transgene expression. An ideal vector would provide local transgene expression at the site of the disease only when the disease is active. Recombinant adeno-associated virus (rAAV) appears to possess these important qualities. We monitored the effects of inflammatory cytokines on transgene expression in human rheumatoid arthritis fibroblast-like synoviocytes (FLS) infected with rAAV. Synovial cell cultures were infected with rAAV under control of the cytomegalovirus (CMV) promoter in the presence or absence of TNF|[alpha]|, IL-1|[beta]|, and/or IL-6. These cytokines were found to act synergistically to increase transgene expression in rAAV infected FLS up to 1000 fold. The enhanced expression required the continued presence of cytokines, although cytokine removal and re-addition demonstrated a remarkable ability of the cytokines to regulate transgene expression. The effect was most pronounced on cells infected with a double stranded version of AAV in which a rate-limiting step of viral transduction (second strand synthesis) is bypassed, and the effect was not promoter specific, as similar results were obtained using rAAV under control of the chicken beta actin promoter. mRNA levels of the transgene were demonstrated to increase up to 25-fold upon cytokine addition. The observed phenomenon was also phosphatidylinositol 3-kinase (PI3K) dependent, as addition of wortmannin reversibly inhibited cytokine-mediated increases in transgene expression. These results suggest that expression of a therapeutic transgene can be controlled by the presence of inflammation following AAV-mediated gene transfer, making AAV an attractive gene transfer vector for chronic inflammatory diseases such as rheumatoid arthritis.
Aicardi–Goutières syndrome harbours abundant systemic and brain-reactive autoantibodies
Authors: Eloy Cuadrado, Adeline Vanderver, Kristy J Brown, Annie Sandza, Asako Takanohashi, Machiel H Jansen, Jasper Anink, Brian Herron, Simona Orcesi, Ivana Olivieri, Gillian I Rice, Eleonora Aronica, Pierre Lebon, Yanick J Crow, Elly M Hol, Taco W Kuijpers
Journal: Annals of the Rheumatic Diseases (2014)

Aicardi-Goutières syndrome (AGS) is an autoimmune disorder that shares similarities with systemic lupus erythematous. AGS inflammatory responses specially target the cerebral white matter. However, it remains uncertain why the brain is the most affected organ, and little is known about the presence of autoantibodies in AGS. Here, we aim to profile specific autoantibodies in AGS and to determine whether these autoantibodies target cerebral epitopes.Using a multiplex microarray, we assessed the spectrum of serum autoantibodies in 56 genetically confirmed patients with AGS. We investigated the presence of immunoglobulins in AGS brain specimens using immunohistochemistry and studied the reactivity of sera against brain epitopes with proteomics.Serum from patients exhibited high levels of IgGs against nuclear antigens (gP210, Nup62, PCNA, Ro/SSA, Sm/RNP complex, SS-A/SS-B), components of the basement membrane (entactin, laminin), fibrinogen IV and gliadin. Upon testing whether antibodies in AGS could be found in the central nervous system, IgGs were identified to target in vivo endothelial cells in vivo and astrocytes in brain sections of deceased patients with AGS. Using a proteomics approach, we were able to confirm that IgGs in serum samples from AGS patients bind epitopes present in the cerebral white matter.Patients with AGS produce a broad spectrum of autoantibodies unique from other autoimmune diseases. Some of these autoantibodies target endothelial cells and astrocytes in the brain of the affected patients, perhaps explaining the prominence of neurological disease in the AGS phenotype.
Inactivity and obesity
Authors: Des Spence
Journal: BMJ (2011)

The wine always disinhibits your inner voice: “Boring, boring, boring,” you yell. Dinner parties can be dull affairs. Suggesting that private schools are “socially elitist and divisive” is social Semtex to liven things up. Concerned and liberal middle class parents are put on the rack and bleat in pain, their moral joints pulled out of sockets as they seek to justify why they educate their children privately. Finally they rasp a choked “I just want the best for my children.” This position needs no defending.

The privately educated …
PATHOLOGY OF UVEITIS.
Authors: WILLIAM H. WILDER
Journal: JAMA (1902)

Properly speaking, the term uveitis should be applied to an inflammation of any portion of the uveal tract which embraces iris, ciliary body and choroid; and an inflammatory process in any one of these structures, if severe and protracted, may involve the other divisions. Hence we frequently have cyclitis and choroiditis associated with severe iritis, if not caused by it, and likewise in suppurative choroiditis and even in certain types of protracted plastic choroiditis the iris and ciliary body become affected. Thinking it better to limit the subject, this paper will consider particularly lesions of the choroid. <h3>CLASSIFICATION.</h3> A satisfactory pathologic classification of the forms of choroiditis is difficult, for although we recognize that these forms differ as to their etiology, the situations of their lesions, and their clinical appearances, yet their pathologic anatomy is by no means so varied. However, the usual division into purulent or suppurative choroiditis and
OC-029 Radiofrequency Ablation (Rfa) Confers Sustained Benefit for Squamous High Grade Dysplasia (Hgd) and Early Squamous Cell Carcinoma (Scc) in Patients who do not Progress following First Treatment
Authors: R J Haidry, M Banks, M Butt, A Gupta, J Louis-Auguste, J Dunn, H L Smart, P Bhandari, L-A Smith, R Willert, G Fullarton, M di Pietro, I Penman, R Narayanasamy, J Morris, D O’Toole, M Novelli, C Gordon, L Lovat
Journal: Gut (2013)

<h3>Introduction</h3> Oesphageal SCC carries a poor prognosis. Squamous HGD is the precursor lesion to SCC. Risk of progression to SCC with HGD can be 65% at 5 years. RFA is a minimally invasive technique with proven efficacy for early neoplasia arising in Barrett's oesophagus. We present prospective data from 10 centres in the United Kingdom (UK) HALO registry. <h3>Methods</h3> Superficial lesions were removed by endoscopic mucosal resection (EMR) before RFA. Treatment consisted of a single ablation at 12J/cm2. Patients were followed up 3 months after treatment with biopsies. Those with residual dysplasia underwent further RFA until 12 months when they were assessed for treatment success or failure. Recurrent dysplasia was retreated with EMR/RFA. Primary outcomes were reversal of dysplasia (CR-D) at 12 months. <h3>Results</h3> 26 patients had RFA. Mean length mucosa ablated was 5.3 cm (1–14). 7/26 (27%) had EMR before RFA. Prior EMR did not confer benefit to outcome, nor did baseline disease length. Following first RFA, 6/26 patients (23%) progressed to invasive disease. Only one more patient progressed later in treatment course. CR-D was achieved in 50% at protocol end, mean 1.7 RFA treatments (1–4). 10/13 (77%) with successful RFA at 12 months remain disease free at most recent follow up (median 21 months). Kaplan Meier statistics show 2 years post treatment 68% patients are likely to remain in remission from dysplasia for those with successful outcome at 12 months. 5 patients (19%) required dilatations for oesophageal stricturing. <h3>Conclusion</h3> Squamous HGD &amp; CIS are aggressive pathologies as evidenced by the fact that 23% patients in our cohort progressed to invasive disease despite RFA. However the majority who do not progress early (13/19 patients) achieve benefit &amp; are more likely to have a successful &amp; durable outcome. There is limited experience in the UK with RFA in these patients. Pre RFA EMR for visible lesions is limited in our series. As a result some patients may be under staged prior to RFA which may account for the high rate of progression after first treatment. <h3>Disclosure of Interest</h3> None Declared
Early-Onset Cyclophosphamide-Induced Interstitial Pneumonitis
Authors: Jesse I. Spector
Journal: JAMA (1979)

This article describes three cases of biopsy-proved interstitial pneumonitis secondary to cyclophosphamide therapy. The pulmonary reactions developed after one to three courses of combination chemotherapy in three patients with diffuse histiocytic lymphoma. Resolution of the pulmonary infiltrates and blood gas value abnormalities followed discontinuation of use of this drug without recurrence when chemotherapy regimens excluding cyclophosphamide were subsequently used. Prednisone was given to all patients after the diagnosis was made, but its role in the resolution of the toxic changes is uncertain. The potential for early onset of cyclophosphamide-induced interstitial pneumonitis has not been previously stressed, but should lead to vigorous investigation of pulmonary reactions occurring at any time after initiation of therapy with this drug. (<i>JAMA</i>242:2852-2854, 1979)