tbuckley/cabot-search huggingface dataset:
Cyclooxygenases, Thromboxane, and Atherosclerosis
Authors: Karine M. Egan, Miao Wang, Margaret B. Lucitt, Alicia M. Zukas, Ellen Puré, John A. Lawson, Garret A. FitzGerald
Journal: Circulation (2005)

Antagonism or deletion of the receptor (the TP) for the cyclooxygenase (COX) product thromboxane (Tx)A2, retards atherogenesis in apolipoprotein E knockout (ApoE KO) mice. Although inhibition or deletion of COX-1 retards atherogenesis in ApoE and LDL receptor (LDLR) KOs, the role of COX-2 in atherogenesis remains controversial. Other products of COX-2, such as prostaglandin (PG) I2 and PGE2, may both promote inflammation and restrain the effects of TxA2. Thus, combination with a TP antagonist might reveal an antiinflammatory effect of a COX-2 inhibitor in this disease. We addressed this issue and the role of TxA2 in the promotion and regression of diffuse, established atherosclerosis in Apobec-1/LDLR double KOs (DKOs).TP antagonism with S18886, but not combined inhibition of COX-1 and COX-2 with indomethacin or selective inhibition of COX-2 with Merck Frosst (MF) tricyclic, retards significantly atherogenesis in DKOs. Although indomethacin depressed urinary excretion of major metabolites of both TxA2, 2,3-dinor TxB2 (Tx-M), and PGI2, 2,3-dinor 6-keto PGF(1alpha) (PGI-M), only PGI-M was depressed by the COX-2 inhibitor. None of the treatments modified significantly the increase in lipid peroxidation during atherogenesis, reflected by urinary 8,12-iso-iPF(2alpha)-VI. Combination with the COX-2 inhibitor failed to augment the impact of TP antagonism alone on lesion area. Rather, analysis of plaque morphology reflected changes consistent with destabilization of the lesion coincident with augmented formation of TxA2. Despite a marked effect on disease progression, TP antagonism failed to induce regression of established atherosclerotic disease in this model.TP antagonism is more effective than combined inhibition of COX-1 and COX-2 in retarding atherogenesis in Apobec-1/LDLR DKO mice, which perhaps reflects activation of the receptor by multiple ligands during disease initiation and early progression. Despite early intervention, selective inhibition of COX-2, alone or in combination with a TP antagonist, failed to modify disease progression but may undermine plaque stability when combined with the antagonist. TP antagonism failed to induce regression of established atherosclerotic disease. TP ligands, including COX-1 (but not COX-2)-derived TxA2, promote initiation and early progression of atherogenesis in Apobec-1/LDLR DKOs but appear unimportant in the maintenance of established disease.
Homicide by quackery
Authors: A. R. Holder
Journal: JAMA (1972)

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
THE EFFECTS OF RADIUM AND ROENTGEN RAYS
Authors: C. F. Charlton
Journal: JAMA (1926)

To the Editor:  —InThe Journal, November 6, Dr. A. U. Desjardins reaffirms his well known position on the effect of radium and roentgen rays. This discourse is reactionary against the general belief in a physiologic response to irradiation (Editorial, Am. J. Roentgenol ., August, 1924).  Ewing stated the case clearly in the Caldwell Lecture of 1925 when he said that if direct action had been depended on, radiation therapy would have come to an end years ago when Francis Carter Wood showed that it required seven times the erythema dose to kill certain mouse cancers in vitro.  Again, Murphy of the Rockefeller Institute inadvertently experienced the same result. This led him to investigate the subject extensively. He exposed a cancer culture to massive doses of roentgen ray every five weeks for a year and a half, then to find only a transitory interference with growth when it was grafted. On
Approaches to environmental exposure assessment in children.
Authors: V M Weaver, T J Buckley, J D Groopman
Journal: Environmental Health Perspectives (1998)

An improved understanding of the contribution made by environmental exposures to disease burden in children is essential, given current increasing rates of childhood illnesses such asthma and cancer. Children must be routinely included in environmental research. Exposure assessment, both external (e.g., air, water) and internal dose (e.g., biomarkers), is an integral component of such research. Biomarker measurement has some advantages that are unique in children. These include assessment of potentially increased absorption because of behaviors that differ from adults (i.e., hand-to-mouth activity); metabolite measurement, which can help identify age-related susceptibility differences; and improved assessment of dermal exposure, an important exposure route in children. Environmental exposure assessment in children will require adaption of techniques that are currently applied in adult studies as well as development of tools and validation of strategies that are unique for children. Designs that focus on parent-child study units provide adult comparison data and allow the parent to assist with more complex study designs. Use of equipment that is sized appropriately for children, such as small air pumps and badge monitors, is also important. When biomarkers are used, biologic specimens that can be obtained noninvasively are preferable. Although the current need is primarily for small focused studies to address specific questions and optimize research tools, the future will require establishment of large prospective cohorts. Urban children are an important study cohort because of relatively high morbidity observed in the urban environment. Finally, examples of completed or possible future studies utilizing these techniques are discussed for specific exposures such as benzene, environmental tobacco smoke, aflatoxin, volatile organic compounds, and polycyclic aromatic hydrocarbons.
Dual targeting of the tumor and its associated vasculature using a single bispecific chimeric antigen receptor molecule
Authors: Tiara Byrd, Kristen Fousek, Antonella Pignata, Amanda Wakefield, Zakaria Grada, Kevin Aviles-Padilla, Bradley S Fletcher, Meenakshi Hegde, Brad St Croix, Nabil Ahmed
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts We have previously demonstrated the efficacy of HER2 specific chimeric antigen receptor (CAR) T cells in animal models of human cancer. While HER2 CAR T cells induced tumor regression, tumors recurred in a subset of animals. Lytic co-targeting of the tumor endothelium could
Prognostic Accuracy of WHO Growth Standards to Predict Mortality in a Large-Scale Nutritional Program in Niger
Authors: Nathanael Lapidus, Francisco J Luquero, Valérie Gaboulaud, Susan Shepherd, Rebecca F Grais
Journal: PLoS Medicine (2009)

Important differences exist in the diagnosis of malnutrition when comparing the 2006 World Health Organization (WHO) Child Growth Standards and the 1977 National Center for Health Statistics (NCHS) reference. However, their relationship with mortality has not been studied. Here, we assessed the accuracy of the WHO standards and the NCHS reference in predicting death in a population of malnourished children in a large nutritional program in Niger.We analyzed data from 64,484 children aged 6-59 mo admitted with malnutrition (<80% weight-for-height percentage of the median [WH]% [NCHS] and/or mid-upper arm circumference [MUAC] <110 mm and/or presence of edema) in 2006 into the Médecins Sans Frontières (MSF) nutritional program in Maradi, Niger. Sensitivity and specificity of weight-for-height in terms of Z score (WHZ) and WH% for both WHO standards and NCHS reference were calculated using mortality as the gold standard. Sensitivity and specificity of MUAC were also calculated. The receiver operating characteristic (ROC) curve was traced for these cutoffs and its area under curve (AUC) estimated. In predicting mortality, WHZ (NCHS) and WH% (NCHS) showed AUC values of 0.63 (95% confidence interval [CI] 0.60-0.66) and 0.71 (CI 0.68-0.74), respectively. WHZ (WHO) and WH% (WHO) appeared to provide higher accuracy with AUC values of 0.76 (CI 0.75-0.80) and 0.77 (CI 0.75-0.80), respectively. The relationship between MUAC and mortality risk appeared to be relatively weak, with AUC = 0.63 (CI 0.60-0.67). Analyses stratified by sex and age yielded similar results.These results suggest that in this population of children being treated for malnutrition, WH indicators calculated using WHO standards were more accurate for predicting mortality risk than those calculated using the NCHS reference. The findings are valid for a population of already malnourished children and are not necessarily generalizable to a population of children being screened for malnutrition. Future work is needed to assess which criteria are best for admission purposes to identify children most likely to benefit from therapeutic or supplementary feeding programs.
The Postmenopausal Estrogen/Progestin Interventions Trial-Reply
Authors: Elizabeth Barrett-Connor
Journal: JAMA (1995)

In Reply.  —Dr Abrams states that endometrial cancer was a known complication of unopposed estrogen at the time PEPI began, and that despite annual endometrial biopsies, the risk was unacceptable and led to seven hysterectomies.  The rationale for the unopposed estrogen arm was to determine whether risk factor changes were different with this regimen compared with estrogen and progestin, because nearly all previous observational studies suggesting cardioprotection were based on women who took estrogen without progestin. In addition, progestin-associated symptoms are common reasons why women fail to continue estrogen when it is prescribed with a progestin. Therefore, we thought it was extremely important to contrast unopposed estrogen with opposed estrogen regimens.  The published literature showed that estrogen-associated endometrial cancer was rare and preceded by adenomatous or atypical hyperplasia. Adenomatous hyperplasia was reported to be reversible after estrogen withdrawal and 3 months of treatment with medroxyprogesterone acetate (10 mg/d). No invasive
The Dynamics of the Human Infant Gut Microbiome in Development and in Progression toward Type 1 Diabetes
Authors: Aleksandar D. Kostic, Dirk Gevers, Heli Siljander, Tommi Vatanen, Tuulia Hyötyläinen, Anu-Maaria Hämäläinen, Aleksandr Peet, Vallo Tillmann, Päivi Pöhö, Ismo Mattila, Harri Lähdesmäki, Eric A. Franzosa, Outi Vaarala, Marcus de Goffau, Hermie Harmsen, Jorma Ilonen, Suvi M. Virtanen, Clary B. Clish, Matej Orešič, Curtis Huttenhower, Mikael Knip, Ramnik J. Xavier
Journal: Cell Host & Microbe (2015)
Hemodynamic consequences of afterload reduction in patients with chronic aortic regurgitation.
Authors: J L Bolen, E L Alderman
Journal: Circulation (1976)

Nitroprusside was used to reduce afterload in 13 patients with isolated, severe aortic regurgitation. The drug significantly lowered mean aortic pressure, pulse pressure, left ventricular end-diastolic pressure and left ventricular volume. Total ventricular, or angiographic, cardiac index was generally unaffected, but forward cardiac index was improved significantly in 8 of 13 patients. Augmentation of forward cardiac index was seen in patients with subnormal resting forward cardiac index, in patients with decidedly elevated end-diastolic pressure, and in those with depressed resting ejection fractions. Regurgitant fraction fell with nitroprusside in six patients and remained unchanged in seven. Total stroke work index was diminished in all patients. These data show that afterload reduction in patients with severe aortic regurgitation may improve hemodynamics by reducing aortic regurgitation or by improving ventricular pump function. The lowered total stroke work, reduced ventricular size and improved forward cardiac index imply that afterload reduction may benefit left ventricular failure and delay progressive ventricular dysfunction in patients with aortic regurgitation.
Gradient of Disability across the Socioeconomic Spectrum in the United States
Authors: Meredith Minkler, Esme Fuller-Thomson, Jack M. Guralnik
Journal: New England Journal of Medicine (2006)

Although the relationship between extreme poverty and poor health among older adults has long been recognized, less attention has been devoted to investigating whether a gradient in disability exists in the United States among persons with middle-class and upper-class incomes. We attempted to determine whether a gradient in functional limitation exists across the full spectrum of income among persons 55 years of age or older.
Ulcerative colitis--a disease characterised by the abnormal colonic epithelial cell?
Authors: P R Gibson, E van de Pol, P J Barratt, W F Doe
Journal: Gut (1988)

The leakiness of the cell membranes of colonic epithelial cells isolated by the collagenase/Dispase technique from normal or diseased colons was assessed in a 4 h 51Cr release assay. Cells from normal, adenoma bearing or cancer bearing colons showed 51Cr release of 8% or less in almost all of 46 cell populations tested. In contrast, cells from mucosa affected by ulcerative colitis [11.9 (4.3%) n = 23] or Crohn9s disease [8.4 (2.7%) n = 18] released significantly more 51Cr than the non-inflamed groups. Values are expressed as mean (SD). Overall, release values were greater in ulcerative colitis than Crohn9s disease (p less than 0.01). In Crohn9s disease, cells obtained from histologically inflamed mucosa released significantly more 51Cr [9.7 (2.5%) n = 11] than those from non-inflamed mucosa [6.4 (1.5%) n = 7, p less than 0.02] whereas, in ulcerative colitis, abnormal release values were found in 8 of 13 cell populations isolated from mucosa showing no histological evidence of active disease. In five patients with distal ulcerative colitis, cells from mucosa not apparently involved demonstrated normal 51Cr release in four of five studies despite abnormal release from cells from involved mucosa suggesting that a diffuse abnormality of the colonic epithelial cell is not usually present. These data indicate that chronic mucosal inflammation per se is associated with abnormalities of the colonic epithelial cell but that, in ulcerative colitis, the abnormality remains in many patients with quiescent disease. Identification of the local factors responsible for such an abnormality may contribute to an understanding of the pathogenesis of ulcerative colitis.
Superscan-like Hypermetabolic Lesions on Delayed FDG PET/CT Imaging in a Patient With Lung Cancer
Authors: Gang Cheng, Abass Alavi, Esther Lim, Scott R. Akers
Journal: Clinical Nuclear Medicine (2012)

A 69-year-old man with a lung mass underwent multiple-time-point FDG PET/CT imaging for diagnostic evaluation. The initial PET imaging (performed at 1 hour after tracer injection) revealed equivocal bone marrow uptake in the right iliac bone and proximal femurs in addition to lung and mediastinal lesions. The 3-hour delayed PET imaging, however, demonstrated widespread bone marrow metastases. Biopsies of the right lung mass and right iliac bone marrow were later performed and revealed a poorly differentiated squamous cell carcinoma in both sites. This case indicates the value of delayed FDG PET in detecting superscan-like hypermetabolic bone marrow lesions in patients with lung cancer.
No Evidence for an mtDNA Role in Sperm Motility: Data from Complete Sequencing of Asthenozoospermic Males
Authors: Luísa Pereira, João Gonçalves, Ricardo Franco-Duarte, Júlia Silva, Tiago Rocha, Christiane Arnold, Martin Richards, Vincent Macaulay
Journal: Molecular Biology and Evolution (2007)

The first complete mitochondrial DNA (mtDNA) sequences (∼16,569 bp) in 20 patients with asthenozoospermia and a comparison with 23 new complete mtDNA sequences in teratoasthenozoospermic individuals, confirmed no sharing of specific polymorphisms or specific mitochondrial lineages between these individuals. This is strong evidence against the accepted claim of a major role played by mtDNA in male fertility, once supported by haplogroup association studies based on the screening of hypervariable region I. The hypothesis of maternally driven selection acting in male reproductive success must thus be treated with caution.
On Drainage in Ovariotomy
Authors: G. G. Bantock
Journal: BMJ (1877)

in parts with cavities, the upper lobe containing one extending throughout its wanhole length, and communicating by the above-named openings with the pleura.The right lung was adherent at the apex.The upper lobe wres full of caseous pneumonia, and contained a small cavity at the top.Caseous masses were found in the middle lobe, along its upper border, extending seemingly from certain centres.The lower lobe was much congested, and contained a few miliary tubercles.The heart weighed seven ounces and was fatty, but the valves were healthy.The liver was enlarged, of nutmeggy consistence, and weighed three pounds.The spleen waons amyloid.The kidneys and other organs were healthy.This as a fair instance of scrofulous pneumonia, and exemplified the strik;ing features of this variety of consumption, which may be summed up as follows.I. The intensity of the pyrexia and rapid emaciation.2. The acuteness of the disorganising processes, excavation quickly succeeding consolidation.3. The inflammatory nature of the processes, and the rarity of miliary tubercle.4. The absence of fibrosis.5.The occurrence of pneumothorax, owing to two causes:-i.The size of the cavities formed ; 2. The absence of pleural adhesions.6.The tendency of the disease to localise itself in the lungs, and the freedom of other organs, such as the intestines and the serous mem- branes, from secondary products.
Unscientific Administration Protested
Authors: David H. Spodick
Journal: JAMA (1984)

To the Editor.—  Dr Lundberg's editorial entitled Why Not Scientific Administration? is right on the mark. As a long-time advocate of controlled clinical trials of therapy and diagnosis, 1-4 I found it easy to appreciate Dr Lundberg's appropriate extension of the principle in his concise, pithy essay.  Too often, courses of action have been advocated, promulgated, and implemented without an appropriate test of their cost-benefit characteristics, let alone whether there is any benefit at all over existing or alternate approaches. Dr Lundberg correctly cites the federal plunge into this area with diagnostic-related groups. An analogous situation is in undergraduate education, where all kinds of experiments were inflicted on students without prior testing (where, for example, is the new math?).  Unfortunately, the current stampede to unconsidered and ill-considered regulations was not concocted by well-meaning advanced social thinkers in Washington. It is receiving an unusual push from corporate private enterprise with its
New Syndrome of Paraganglioma and Somatostatinoma Associated With Polycythemia
Authors: Karel Pacak, Ivana Jochmanova, Tamara Prodanov, Chunzhang Yang, Maria J. Merino, Tito Fojo, Josef T. Prchal, Arthur S. Tischler, Ronald M. Lechan, Zhengping Zhuang
Journal: Journal of Clinical Oncology (2013)

The occurrence of ≥ two distinct types of tumors, one of them paraganglioma (PGL), is unusual in an individual patient, except in hereditary cancer syndromes.Four unrelated patients were investigated, with thorough clinical evaluation. Plasma and tissue catecholamines and metanephrines were measured by high-performance liquid chromatography. Anatomic and functional imaging were performed for tumor visualization. Germline and tumor tissue DNA were analyzed for hypoxia-inducible factor 2 alpha (HIF2A) mutations. The prolyl hydroxylation and stability of the mutant HIF2α protein, transcriptional activity of mutant HIF2A, and expression of hypoxia-related genes were also investigated. Immunohistochemical staining for HIF1/2α was performed on formalin-fixed, paraffin-embedded tumor tissue.Patients were found to have polycythemia, multiple PGLs, and duodenal somatostatinomas by imaging or biochemistry with somatic gain-of-function HIF2A mutations. Each patient carried an identical unique mutation in both types of tumors but not in germline DNA. The HIF2A mutations in these patients were clustered adjacent to an oxygen-sensing proline residue, affecting HIF2α interaction with the prolyl hydroxylase domain 2-containing protein, decreasing the hydroxylation of HIF2α, and reducing HIF2α affinity for the von Hippel-Lindau protein and its degradation. An increase in the half-life of HIF2α was associated with upregulation of the hypoxia-related genes EPO, VEGFA, GLUT1, and END1 in tumors.Our findings indicate the existence of a new syndrome with multiple PGLs and somatostatinomas associated with polycythemia. This new syndrome results from somatic gain-of-function HIF2A mutations, which cause an upregulation of hypoxia-related genes, including EPO and genes important in cancer biology.
Changes in plasma catecholamines and dopamine beta-hydroxylase after corrective surgery for coarctation of the aorta.
Authors: C R Benedict, D G Grahame-Smith, A Fisher
Journal: Circulation (1978)

In six patients within 12 hours of surgical correction of aortic coarctation there was a 750% increase in plasma noradrenaline concentrations accompanied by an increase in systolic and diastolic blood pressures. The magnitude of the postoperative increase in noradrenaline concentrations was related to the preoperative level of the pressure gradient across the coarctation. Six months after operation plasma noradrenaline concentrations were still significantly elevated. In nine patients who underwent other types of major surgery there was a small increase in plasma noradrenaline concentrations and a return to levels within the normal range within 24 hours. Various explanations for the rise in plasma noradrenaline concentrations are considered. In particular the possibility is raised that after surgical correction of aortic coarctation the increased levels indicate a marked increase in sympathetic nervous system activity; this may be mediated by baroreceptor mechanisms and may persist for up to six months after surgery.