tbuckley/cabot-search huggingface dataset:
A Phase I Trial of Single-Agent Reolysin in Patients with Relapsed Multiple Myeloma
Authors: Douglas W. Sborov, Gerard J. Nuovo, Andrew Stiff, Thomas Mace, Gregory B. Lesinski, Don M. Benson, Yvonne A. Efebera, Ashley E. Rosko, Flavia Pichiorri, Michael R. Grever, Craig C. Hofmeister
Journal: Clinical Cancer Research (2014)

Reolysin, a proprietary isolate of reovirus type III dearing, enters and preferentially induces apoptosis of malignant cells. RAS pathway activation has been associated with more efficient reoviral infectivity and enhanced oncolysis. Reovirus is currently in advanced solid tumor phase I-II trials; no clinical trials have been conducted in patients with hematologic malignancies.A phase I trial treated 12 relapsed myeloma patients at two dose levels. Reolysin was infused daily for 5 days every 28 days. Bone marrow specimens were examined by in situ-based hybridization (ISH) for CD138, p38, caspase-3, reoviral RNA, and capsid protein at screening and cycle 1 day 8. Junctional adhesion molecule 1 (JAM-1) and cancer upregulated gene 2 (CUG2) were evaluated in patient samples and multiple myeloma cell lines. Neutralizing anti-reovirus antibody assay was performed weekly during cycle 1.There were no dose-limiting toxicities, patients reached the 3 × 10(10) TCID50 daily on days 1 to 5 dose level, and grade 3 laboratory toxicities included neutropenia, thrombocytopenia, and hypophosphatemia. ISH demonstrated reoviral genome confined in multiple myeloma cells. Reoviral capsid protein and caspase-3 were rarely identified within reoviral RNA-positive cells. The longest durations of stable disease were 4, 5, and 8 months.Treatment with single-agent Reolysin was well tolerated and associated with avid reoviral RNA myeloma cell entry but only minimal intracellular reoviral protein production within multiple myeloma cells. Our data support that in multiple myeloma cells, Reolysin-induced oncolysis requires combination therapy, similar to other cancers.
Aortic Root Dilatation as a Cause of Isolated, Severe Aortic Regurgitation
Authors: MARY J. ROMAN
Journal: Annals of Internal Medicine (1987)

To evaluate the relation of aortic root dilatation to aortic regurgitation, we examined clinical, echocardiographic, and radionuclide cineangiographic findings in 102 patients with severe aortic regurgitation. Aortic root dilatation was the only apparent cause in 31 patients (30%), exceeding in prevalence any valvular cause, and was independently associated only with older age (p less than 0.001). Echocardiography showed dilatation to be either localized to the sinuses of Valsalva or to be generalized. At initial evaluation, patients with generalized dilatation had severer abnormalities of left ventricular size and function than those with localized or no dilatation. Aortic valves were subsequently replaced in more patients with generalized than localized dilatation during 28 +/- 17 month follow-up (9 of 15 patients compared with 2 of 15, p less than 0.03). Thus, idiopathic aortic root dilatation is the commonest definable cause of severe aortic regurgitation; aortic root dilatation is associated independently with age but not blood pressure; and generalized aortic root dilatation is associated with marked ventricular dilatation, hypertrophy, and dysfunction.
Approaches to behaviour change within health promotion
Authors: Jim McKenna
Journal: British Journal of Sports Medicine (2010)

Behaviour change continues to be a central concern for health promoters, irrespective of where they do their work. This presentation will address how recent developments in understanding of human decision-making have revised understanding about behaviour change. These developments have been made by economists, social scientists and psychologists, meaning that their relevance to health promotion has yet to be optimised. Importantly, these new insights highlight the importance of health promoters not only continuing to address rationale decision-making, but also acting to optimise the value of contextual changes that hinge on instinctive, automated cognitive functions. This presentation will offer (A) a number of challenges and (B) suggestions about how to respond to these new discoveries across a range of behaviour change scenarios.
Essential role of sphingosine 1–phosphate receptor 2 in pathological angiogenesis of the mouse retina
Authors: Athanasia Skoura, Teresa Sanchez, Kevin Claffey, Suzanne M. Mandala, Richard L. Proia, Timothy Hla
Journal: Journal of Clinical Investigation (2007)

Sphingosine 1–phosphate (S1P), a multifunctional lipid mediator that signals via the S1P family of G protein–coupled receptors (S1PR), regulates vascular maturation, permeability, and angiogenesis. In this study, we explored the role of S1P 2 receptor (S1P2R) in normal vascularization and hypoxia-triggered pathological angiogenesis of the mouse retina. S1P2R is strongly induced in ECs during hypoxic stress. When neonatal mice were subjected to ischemia-driven retinopathy, pathologic neovascularization in the vitreous chamber was suppressed in S1p2–/– mice concomitant with reduction in endothelial gaps and inflammatory cell infiltration. In addition, EC patterning and normal revascularization into the avascular zones of the retina were augmented. Reduced expression of the proinflammatory enzyme cyclooxygenase-2 (COX-2) and increased expression of eNOS were observed in the S1p2–/– mouse retina. S1P2R activation in ECs induced COX-2 expression and suppressed the expression of eNOS. These data identify the S1P2R-driven inflammatory process as an important molecular event in pathological retinal angiogenesis. We propose that antagonism of the S1P2R may be a novel therapeutic approach for the prevention and/or treatment of pathologic ocular neovascularization.
Efficacy, safety, and therapeutic relevance of transthoracic aspiration with ultrathin needle in nonventilated nosocomial pneumonia.
Authors: J Dorca, F Manresa, L Esteban, B Barreiro, E Prats, J Ariza, R Verdaguer, F Gudiol
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

In order to determine the potential indications of transthoracic needle aspiration (TNA) using the ultrathin 25G needle for the diagnosis of nonopportunistic lung infections, we prospectively analyzed the diagnostic efficacy, safety, and therapeutic implications of its results in 97 patients with nonventilated nosocomial pneumonias (NVNP). The sensitivity of TNA was 60.9%. Specificity and positive predictive value (PPV) were 100%. Negative predictive value (NPV) was 34.1%. The complications in the studied cases were nil in 89 cases (91.8%), transient hemoptoic expectoration (< 10 ml) in five (5.2%), and self-limited partial pneumothorax in three (3.1%). No complications needing treatment were observed. On the basis of a positive TNA result, the initial antibiotic treatment was modified in 29 of 97 (29.9%) cases. In twelve of these, the empirical antibiotic regimen was demonstrated to be ineffective. We conclude that, using the 25G needle, TNA has a good diagnostic efficacy and is a safe procedure for the etiologic investigation of NVNP. A positive TNA result has significant therapeutic relevance, even in cases where broad-spectrum antibiotics are empirically prescribed.
Exposure, metabolism, and toxicity of rare earths and related compounds.
Authors: S Hirano, K T Suzuki
Journal: Environmental Health Perspectives (1996)

For the past three decades, most attention in heavy metal toxicology has been paid to cadmium, mercury, lead, chromium, nickel, vanadium, and tin because these metals widely polluted the environment. However, with the development of new materials in the last decade, the need for toxicological studies on those new materials has been increasing. A group of rare earths (RE) is a good example. Although some RE have been used for superconductors, plastic magnets, and ceramics, few toxicological data are available compared to other heavy metals described above. Because chemical properties of RE are very similar, it is plausible that their binding affinities to biomolecules, metabolism, and toxicity in the living system are also very similar. In this report, we present an overview of the metabolism and health hazards of RE and related compounds, including our recent studies.
Calpain mediates pulmonary vascular remodeling in rodent models of pulmonary hypertension, and its inhibition attenuates pathologic features of disease
Authors: Wanli Ma, Weihong Han, Peter A. Greer, Rubin M. Tuder, Haroldo A. Toque, Kevin K.W. Wang, R. William Caldwell, Yunchao Su
Journal: Journal of Clinical Investigation (2011)

Pulmonary hypertension is a severe and progressive disease, a key feature of which is pulmonary vascular remodeling. Several growth factors, including EGF, PDGF, and TGF-β1, are involved in pulmonary vascular remodeling during pulmonary hypertension. However, increased knowledge of the downstream signaling cascades is needed if effective clinical interventions are to be developed. In this context, calpain provides an interesting candidate therapeutic target, since it is activated by EGF and PDGF and has been reported to activate TGF-β1. Thus, in this study, we examined the role of calpain in pulmonary vascular remodeling in two rodent models of pulmonary hypertension. These data showed that attenuated calpain activity in calpain-knockout mice or rats treated with a calpain inhibitor resulted in prevention of increased right ventricular systolic pressure, right ventricular hypertrophy, as well as collagen deposition and thickening of pulmonary arterioles in models of hypoxia- and monocrotaline-induced pulmonary hypertension. Additionally, inhibition of calpain in vitro blocked intracellular activation of TGF-β1, which led to attenuated Smad2/3 phosphorylation and collagen synthesis. Finally, smooth muscle cells of pulmonary arterioles from patients with pulmonary arterial hypertension showed higher levels of calpain activation and intracellular active TGF-β. Our data provide evidence that calpain mediates EGF- and PDGF-induced collagen synthesis and proliferation of pulmonary artery smooth muscle cells via an intracrine TGF-β1 pathway in pulmonary hypertension.
919-9 Comparative Angioscopic Findings After Rotational Atherectomy and Balloon Angioplasty
Authors: Hélème Eltchaninoff, Alain Cribier, René Koning, Valérie Sicard, Brahim Baala, Philippe Dequenne, Brice Letac, Charles Chan, Arthur Tan
Journal: Journal of the American College of Cardiology (1995)
Group 5 determination in Pooideae grass pollen extracts by monoclonal antibody‐based ELISA. Correlation with biologic activity
Authors: J. Ramírez, T. M. Obispo, O. Duffort, J. A. Carpizo, M. J. Chamorro, D. Barber, H. Ipsen, J. Carreira, M. Lombardero
Journal: Allergy (1997)

A solid‐phase, monoclonal antibody‐based ELISA was set up to quantitale group 5 allergens in pollen extracts of wild and cultivated Pooideae grasses. The method was able to evaluate group 5 concentration in mass units with a sensitivity in the ng/ml range and a practical working range of 1–100 ng/ml. The group 5 ELISA was compared with rocket immunoelectrophoresis for determination of allergen levels in several Phleumpratense extracts, and a very good quantitative correlation was found ( r =0.98; P &lt;0.0001). A highly significant correlation ( r &gt;0.8) was also obtained in comparing allergenic potency determined by RAST inhibition to group 5 content in several wild and cultivated grass species. The results proved the usefulness of the method in the standardization of Pooideae pollen extracts employed in diagnosis and treatment.
The History of Crete
Authors: Selma Harrison Calmes
Journal: JAMA (1991)

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
Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina.
Authors: P Théroux, D Waters, S Qiu, J McCans, P de Guise, M Juneau
Journal: Circulation (1993)

BACKGROUND Antiplatelet therapy with aspirin and antithrombotic therapy with heparin both prevent the complications of unstable angina; however, no definitive data exist on the relative clinical efficacy of the two drugs. METHODS AND RESULTS Aspirin (325 mg bid) or heparin (5000-U intravenous bolus followed by a perfusion titrated to the APTT) were compared in a double-blind randomized trial of 484 patients in two cohorts enrolled sequentially. The study was initiated at admission to hospital at a mean of 8.3 +/- 7.8 hours after the last episode of pain. End points were assessed 5.7 +/- 3.3 days later, when the decision for long-term management was made. Myocardial infarction occurred in 2 (0.8%) of the 240 patients randomized to heparin and in 9 (3.7%) of the 244 randomized to aspirin (P = .035), an odds ratio of 0.22 and a risk difference of 2.9% (95% confidence limits, 0.3% to 5.6%) with heparin. The only death resulted from a myocardial infarction in an aspirin patient. Survival curves with Cox logistic regression analysis showed that the improvement in survival without myocardial infarction with heparin (P = .035) was independent of other baseline characteristics. CONCLUSIONS This study documents that heparin prevents myocardial infarction better than aspirin during the acute phase of unstable angina.
Abstract 1666: Mitochondrial DNA sequence mutations and risk of pancreatic cancer
Authors: Gregory J. Tranah, Ernest T. Lam, Paige M. Bracci, Elizabeth A. Holly
Journal: Cancer Research (2012)

Abstract Although the mitochondrial genome exhibits high mutation rates, common mitochondrial DNA (mtDNA) variation has not been consistently associated with pancreatic cancer. Here, we comprehensively examined mitochondrial genomic variation by sequencing the mtDNA of participants (cases=286, controls=283) in a San Francisco Bay Area pancreatic cancer case-control study. Five common variants were associated with pancreatic cancer at nominal statistical significance (p&amp;lt;0.05) with the strongest finding for mt5460g in the ND2 gene (odds ratio (OR)=3.9, 95% confidence interval (CI)=1.5-10; p=0.004) which encodes an A331T substitution. Haplogroup K was nominally associated with reduced pancreatic cancer risk (OR = 0.32, CI=0.13-0.76; p=0.01) when compared with the most common haplogroup, H. A total of 19 haplogroup-specific rare variants yielded nominal statistically significant associations (p&amp;lt;0.05) with pancreatic cancer risk, with the majority observed in genes involved in oxidative phosphorylation. Weighted-sum statistics were used to identify an aggregate effect of variants in the 22 mitochondrial tRNAs on pancreatic cancer risk (p=0.02). While the burden of singleton variants in the HV2 and 12S RNA regions was three times higher among European haplogroup N cases than controls, the prevalence of singleton variants in ND4 and ND5 was two to three times higher among African haplogroup L cases than in controls. Together, the results of this study provide evidence that aggregated common and rare variants and the accumulation of singleton variants are important contributors to pancreatic cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1666. doi:1538-7445.AM2012-1666
The role of letters in reviewing research
Authors: R. S. Bhopal, A. Tonks
Journal: BMJ (1994)

Yet the directive rolls on and carries in its wake the requirement for "health checks" on night workers.The wide- spread introduction of unfocused health surveillance measures is unjustifiable on grounds of preventive health.Astonishingly, 100 years after the first experiments on shorter working hours and performance" we are still unable to decide whether working long hours is bad for health.Seeing how the European Court of Justice handles it will be interesting.
ACTIVE IMMUNIZATION OF GUINEA PIGS WITH THE VIRUS OF EQUINE ENCEPHALOMYELITIS
Authors: Herald R. Cox, Peter K. Olitsky
Journal: The Journal of Experimental Medicine (1936)

An analysis of the preceding experiments discloses that antiviral bodies are demonstrable not at all or in small amounts in the sera of guinea pigs injected with a quantity of active virus not sufficient to induce immunity against the described intracerebral test for induced resistance. However, neutralizing bodies are found in immune animals, although in low concentration, and are regularly manifested when serum is added to low multiples of infective doses of virus under optimal conditions of time and temperature. Hyperimmune serum, on the other hand, reveals a distinct increase in the amount of antiviral bodies present. Irrespective of the mode of procedure for revealing neutralizing bodies, there does not appear to be any notable difference in the content of such bodies in the serum of animals immunized with active virus or with formolized vaccine in which active virus could not be demonstrated. In other words, the antigenic complexes in active as well as in inactive virus produce similar degrees of antibody reaction. The formolization of virus tissue suspensions, therefore, can be considered as a process whereby the virus is inactivated but the antigenicity of the suspensions is preserved, as is also shown in the preceding paper of this series in tests on tissue immunity. In that article is described the remarkably high degree of tissue immunity which results from injections of inactive virus; now we demonstrate that this resistance is associated with a minimal degree of serum antibody. Finally, the question may well be asked, if practically no antiviral bodies are demonstrable immediately or soon after mixing immune serum and virus, and are recognizable in a tenfold increase when functions of time and temperature are brought into play, whether the bodies are "neutralizing" or the phenomenon is due merely to aggregation of virus particles by the serum. From the recent work on the same virus and immune serum (9) by Merrill, there appears to be warrant for the belief in aggregation of virus particles which in turn diminishes the virus activity to the indicated degree.
Precursors of CD3+CD4+CD8+ cells in the human thymus are defined by expression of CD34. Delineation of early events in human thymic development.
Authors: A Galy, S Verma, A Bárcena, H Spits
Journal: The Journal of Experimental Medicine (1993)

Studies of the most immature T cell progenitors in the human thymus have been hampered by the lack of markers and assays that define these cells. In this report we used a novel human fetal thymic organ culture system to determine the potential of T cell precursors isolated from human postnatal thymus, to differentiate into CD3+ thymocytes, and to investigate early stages of human T cell development. It was found that thymocytes that lack the markers CD3, CD4, and CD8 (triple negative [TN]) can differentiate in an allogeneic organotypic thymic culture. The capacity of TN thymocytes to differentiate was exclusively confined to the CD34+ population. CD34- TN thymocytes failed to differentiate in this system. In contrast, cloned lines of CD3- thymocytes could only be established from CD34- TN thymocytes. Five subsets of CD3- thymocytes were found with the following phenotype: CD1-TN, CD1+TN, CD1+CD4+CD8-, CD1+CD4+CD8 alpha+ beta-, and CD1+CD4+CD8 alpha beta+. These subpopulations expressed decreasing levels of CD34. The CD1-CD3- population expressed the highest levels of CD34 supporting the notion that this population is the most immature T cell precursor in the thymus, whereas the CD1+CD4+CD8 alpha+ beta+ which did not express CD34 seems to be the most mature of these CD3- populations. This notion is supported by the observations that CD34+ cells isolated from fetal liver, which differentiated into T cells in a FTOC, developed into CD3+ cells via CD1- and CD4+CD8- intermediates. Based on these data, we present a model of early stages in human intrathymic development.
Growth Factors in Fibrotic Diseases
Authors: Thomas F. Deuel, Robert M. Senior
Journal: New England Journal of Medicine (1987)

IN this issue Martinet et al.1 report that alveolar macrophages from patients with idiopathic pulmonary fibrosis release a growth-promoting activity similar to platelet-derived growth factor (PDGF), and show that the amount of this activity is four times greater than that of the PDGF-like activity released from alveolar macrophages from normal subjects. Assays of chemotaxis and growth-promoting activity established that the mitogen secreted from macrophages was active, and the identity of the secreted activity was suggested by receptor-competition assays and by blockade of its biologic activity with anti-PDGF serum. The results are important, correlating an increased level of a secreted growth . . .
The Aspect Ratio of Nanoparticle Assemblies and the Spatial Arrangement of Ligands can be Optimized to Enhance the Targeting of Cancer Cells
Authors: Amy M. Wen, Nicole F. Steinmetz
Journal: Advanced Healthcare Materials (2014)

Two are better than one: A novel, bottom-up approach using virus-based nanoparticles is developed for the synthesis of dimers and assemblies up to an aspect ratio of 8. Cell uptake is shown to depend on nanoparticle shape and is enhanced for dimers compared with single particles. Symmetrical rather than topo-selective presentation of RGD peptides further enhances cancer cell targeting.
THE POST-MORTEM STATISTICS OF MIDDLE EAR DISEASE IN YOUNG CHILDREN
Authors: J. Miller
Journal: BMJ (1907)

tered and lncisions made dorsally and ventrally over the distal interphalangeal joint, but only a bead of pus was liberated.Further inclsion,s were made two days later wlthout finding pus.The temperature had now risen to 1030 and the patient
855-3 Correlation between hyperenhancement on delayed contrast enhanced magnetic resonance imaging (MRI) and diastolic function assessed by steady state cine MRI in hypertrophic cardiomyopathy
Authors: Munenobu Motoyasu, Hajime Sakuma, Shoko Uemura, Katsuya Onishi, Tsutomu Okinaka, Naoki Isaka, Kan Takeda, Takeshi Nakano
Journal: Journal of the American College of Cardiology (2004)