tbuckley/cabot-search huggingface dataset:
Experience With Bevacizumab in the Management of Epithelial Ovarian Cancer
Authors: Robert A. Burger
Journal: Journal of Clinical Oncology (2007)

Müllerian duct adenocarcinomas, in particular epithelial ovarian cancers, continue to represent a major source of female cancer-related morbidity and mortality, despite advances in surgical management and innovations in cytotoxic chemotherapy. Angiogenesis-targeted therapy seems to be appropriate for exploration in these disease processes based on a wealth of evidence from preclinical and molecular epidemiology studies. Bevacizumab is a prototypical agent neutralizing vascular endothelial growth factor (VEGF), a critical angiogenic promoter related to tumor progression, malignant effusions, and prognosis in ovarian cancer. Phase II trials have demonstrated the activity of bevacizumab as a single agent and in combination with other modalities such as low-dose metronomic cyclophosphamide. Historical studies have supported these observations. Unique toxicities have been ascribed to the administration of bevacizumab and other anti-VEGF molecules for patients with this disease and other solid tumors. Although most of these toxicities (such as proteinuria, hypertension, and bleeding) are generally mild, and are either self-limiting or controllable, other adverse effects, though uncommon, may be serious (these include arterial thromboembolism, wound healing complications, and GI perforation or fistulae). Phase III trials are now in progress to determine the role of this drug in primary therapy as an adjunct to platinum-taxane chemotherapy. This article reviews the background and rationale for anti-VEGF therapy of ovarian cancer, summarizes efficacy and safety data from phase II trials and historical studies of bevacizumab in this disease, introduces the implementation of bevacizumab in phase III front-line trials, examines controversial aspects related to anti-VEGF therapy, and proposes future directions regarding bevacizumab and other angiogenic growth factor-targeted therapeutics.
Studies on the Relationship Between Insulin Concentrations and Insulin Action
Authors: S Edwin Fineberg, Stephen H Schneider
Journal: Diabetes Care (1982)

The relationship between insulin concentrations and insulin effects was assessed using a 30-min steadystate perfusion of insulin across the human forearm and a 90-min recovery period in 17 normal men. During perfusion, calculated insulin increments in forearm arterial plasma insulin were 87 ± 4 (group I), 161 ± 17 (group II), and 333 ± 55 μU/ml (group III), respectively. Measured venous insulin increments were 33 ± 4, 66 ± 6, and 231 ± 27 μU/ml. During perfusion, venous and arterial increments were linearly related (r = 0.88, P &amp;lt; 0.001). With discontinuation of perfusion, venous increments of insulin became undetectable after 15 min in groups I and II, and after 30 min in group III. Of the total microunits of insulin perfused, 46.0 ± 11.0%, 45.3 ± 9.4%, and 36.5 ± 4.8%, respectively, remained unaccounted for 90 min after perfusion. Effects of insulin on arteriovenous differences of FFA and potassium persisted throughout the recovery period, with peak effects occurring after perfusion for all groups. Estimated interstitial insulin levels in the three groups fell below 10 μU/ml by 45, 60, and 90 min after perfusion, respectively. Although peripheral tissues had a significant capacity to sequester insulin, the persistence of biologic effects was not consistent with increased concentrations within the interstitial spaces. Effects of insulin upon glucose waned first, followed by effects upon potassium and then lipolysis.
Temples and Bathing Ghat at Benares
Authors: Janet M. Torpy
Journal: JAMA (2010)

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 Journals 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 2024 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
Serum cholesterol concentration and mortality from accidents, suicide, and other violent causes
Authors: E Variainen, P Puska, J Pekkanen, J Tuomilehto, J Lonnqvist, C Ehnholm
Journal: BMJ (1994)

To study the association of mortality from accidents, suicides, and other violent deaths with serum cholesterol concentration.Baseline measurements in two randomly chosen independent cohorts were carried out in 1972 and 1977. Mortality was monitored over 10-15 years through the national death registry.Eastern Finland.The two cohorts comprised men (n = 10,898) and women (n = 11,534) born between 1913 and 1947. There were 193 deaths due to accidents, suicides, and violence among men and 43 among women.Mortality from accidents, suicides, and other violent deaths was used as the end point. Deaths from these causes were pooled together in the analyses.Serum cholesterol concentration was not associated with mortality from accidents, suicides, and other violent deaths in the univariate analyses or in the proportional hazards regression analyses including smoking, systolic blood pressure, alcohol drinking, and education. In both genders smoking was more prevalent among those who died from accidents, suicides, and other violent causes than from other causes. Frequent use of alcohol increased mortality from these causes.The risk of accidents, suicides, and other violent deaths was not related to serum cholesterol concentration, whereas such deaths were more prevalent in smokers and alcohol drinkers.
Wind Turbines: A Different Breed of Noise?
Authors: Nate Seltenrich
Journal: Environmental Health Perspectives (2013)

ue Hobart and her husband built their dream home in 2007 on a quiet, wooded lot outside Falmouth, Massachusetts.Five years later they abandoned it.Less than 1,500 feet from the empty house stands a mammoth wind turbine erected three years ago by Notus Clean Energy.Three blades mounted upon the 262-foot tower sweep an area of the sky equal to 1.3 acres, the size of a football field.They are visible through the forest from the house's meticulously landscaped yard.But the problem with the property wasn't the degraded view-at least not for the Hobarts.The problem was the noise.Shortly after the turbine switched on in 2010, Sue began experiencing headaches, dizziness, insomnia, and a ringing in her ears.When she noticed the symptoms briefly disappeared during trips out of town, she began attributing them to the arrival of the turbine.Within two years she was ready to leave.
Familial Excess of Cancer of the Ovary and Other Anatomic Sites
Authors: Henry T. Lynch, William Albano, Lynn Black, Jane F. Lynch, James Recabaren, Robert Pierson
Journal: JAMA (1981)

In a family with a high incidence of cancer, the proband manifested early-onset colon cancer at age 39 years. His mother, her twin sister, and their daughters had ovarian carcinoma. In the proband's sibship, six of eight had cancer of differing anatomic sites. The susceptibility to ovarian carcinoma appeared to have been transmitted through the men; one was cancer free while two had cancer. Thus, eight close relatives had ovarian carcinoma. Examinations of 51 blood relatives failed to show cutaneous stigmata or congenital abnormalities of known hereditary cancer or precancer syndromes.
Flawed kinematic models cannot provide insight into the nature of motor variability
Authors: Mark L. Latash, Gregor Schöner
Journal: Behavioral and Brain Sciences (1997)

Plamondon &amp; Alimi's derivation of the kinematic model is mathematically flawed. By simply naming a particular parameter combination “variability,” the model fails to explicate the sources of variability. As a result, the model cannot distinguish between various sources of error, such as those resulting from task demands and those resulting from movement execution.
Visual perceptual limitations on letter position uncertainty in reading
Authors: Marialuisa Martelli, Cristina Burani, Pierluigi Zoccolotti
Journal: Behavioral and Brain Sciences (2012)

Frost presents an explanatory theory of reading that generalizes across several languages, based on a revised role of orthographic coding. Perceptual and psychophysical evidence indicates a decay of letter position encoding as a function of the eccentricity of letters (crowding); this factor may account for some of the differences in the languages considered by Frost.
Vascular Smooth Muscle Cells of H-2K <sup>b</sup> -tsA58 Transgenic Mice
Authors: Elisabeth Ehler, Parmjit S. Jat, Mark D. Noble, Sandra Citi, Annette Draeger
Journal: Circulation (1995)

Background The vascular wall is composed of at least two different populations of smooth muscle cells that are distinct in their structure and protein composition. According to the developmental stage of tissue taken for culture, the ratio between cells of epithelioid phenotype and spindle-shaped cells is variable. In particular, the epithelioid cells display characteristic features associated with immaturity. Because their increased appearance can be observed in endothelial denudation, they represent a dedifferentiated, proliferative smooth muscle cell type with a repair function in vascular injury. Methods and Results To investigate this cellular heterogeneity, we established vascular smooth muscle cell lines from H-2K b -tsA58 transgenic mice. Due to temperature-sensitive expression of the SV 40 large T-antigen in cells derived from this mouse strain, our smooth muscle lines were conditionally immortalized from the onset of their life in culture. Thus, we were able to clone cell lines representing the two different phenotypes described so far. Epithelioid cells derived from newborn animals are characterized by their expression of cytokeratins and the development of tight junctional complexes. Spindle-shaped cells, which could be isolated from newborn or adult animals, corresponded in phenotype and protein expression to smooth muscle cell lines established previously. Conclusions The special properties of vascular smooth muscle cells of the epithelioid phenotype suggest an endothelial replacement function in the course of injury to the vascular wall.
Manual of Psychiatric Therapeutics
Authors: G. Edwards
Journal: BMJ (1976)

This fairly advanced colour atlas of histology continues the tradition of the once famous Atlas and Textbook of Histology and Microscopic Anatomy by Sobotta, and it contains a series of colour-drawings from that work.It comprises 420 illustrations of all the tissues of the body.Most are in colour, the great majority being stained either with haema- toxylin and eosin or with Mallory-azan.
818 HCV-TARGET: A LONGITUDINAL, OBSERVATIONAL STUDY OF NORTH AMERICAN PATIENTS WITH CHRONIC HEPATITIS C (HCV) TREATED WITH BOCEPREVIR OR TELAPREVIR
Authors: M.W. Fried, K.R. Reddy, A.M. Di Bisceglie, D.M. Jensen, I.M. Jacobson, M.S. Sulkowski, N.A. Terrault, N.H. Afdhal, S.C. Gordon, P.J. Pockros, P.Y. Kwo, G.T. Everson, K.E. Sherman, A.J. Muir, B.L. Pearlman, T.G. Stewart, M. Vainorius, J.A. Peter, D.R. Nelson
Journal: Journal of Hepatology (2013)
Abstract 1193: Establishment of patient tumor-derived orthotopic xenograft models of metastatic pediatric germinoma
Authors: Holly B. Lindsay, Mari Kogiso, Lin Qi, Teo Wan Yee, Yulun Huang, Hua Mao, Frank Lin, Patricia Baxter, Jack M. Su, Keita Terashima, Laszlo Perlaky, Ching C. Lau, Donald W. Parsons, Murali Chintagumpala, Xiao-Nan Li
Journal: Cancer Research (2014)

Abstract Despite comprising up to 10% of pediatric CNS tumors, an animal model of intracranial germinoma has not been previously established. Standard of case for germinoma is radiation therapy, with recent evidence that neo-adjuvant chemotherapy may allow reduction of radiation dose, but concern for neuro-cognitive toxicity remains despite the reduction of radiation. A clinically relevant animal model of germinoma would facilitate investigation and discovery of novel agents which may obviate the need for radiation in the future. To develop xenograft mouse models, we implanted germinoma tumor cells from two children with metastatic disease, one from a surgical specimen of a cervical metastatic tumor and the second from disseminated tumor cells in the CSF, directly into the right cerebral hemispheres of NOD-SCID mice. Both patient tumor samples have undergone whole exome sequencing; one of the two models has a germinoma-associated mutation in c-kit. The tumors have been serially passaged in xenografts for 3-5 times, with each passaged tumor maintaining the ability to generate tumors, suggestive of the persistence of viable tumorigenic/tumor stem cells. Data from additional tumor models established by our lab have confirmed molecular and genetic fidelity between xenograft-initiating human brain tumors and their corresponding murine models. The orthotopic location in the mouse brain of the xenograft model should also reasonably replicate the human germinoma tumor microenvironment. Cultured cells are currently growing from both tumor models in order to establish germinoma cell lines. In summary, our orthotopic xenograft murine models of two metastatic pediatric germinomas are the first to be established for this tumor type. These models will allow much needed pre-clinical drug testing of chemotherapeutics and combination therapies as well as further biologic characterization of pediatric germinomas. Citation Format: Holly B. Lindsay, Mari Kogiso, Lin Qi, Teo Wan Yee, Yulun Huang, Hua Mao, Frank Lin, Patricia Baxter, Jack M. Su, Keita Terashima, Laszlo Perlaky, Ching C. Lau, Donald W. Parsons, Murali Chintagumpala, Xiao-Nan Li. Establishment of patient tumor-derived orthotopic xenograft models of metastatic pediatric germinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1193. doi:10.1158/1538-7445.AM2014-1193
Anastomoses between Aorta and Right Pulmonary Artery (Waterston) in Neonates
Authors: L. Henry Edmunds, Noel H. Fishman, Michael A. Heymann, Abraham M. Rudolph
Journal: New England Journal of Medicine (1971)

An anastomosis between the aorta and right pulmonary artery (Waterston operation) was constructed in 10 infants with severe cyanosis within 10 days after birth. Diagnoses after cardiac catheterization and cineangiography were pulmonary atresia with intact ventricular septum (five cases), pulmonary atresia with ventricular septal defect (two), pulmonary atresia with ventricular septal defect and transposition of the great arteries (one), tetralogy of Fallot (one) and tricuspid atresia with intact ventricular septum (one). One infant died five hours after operation and did not have a patent anastomosis. Four infants died six to 14 weeks after operation (two, who had associated lesions, died from chronic congestive heart failure, and two, who were seemingly well, died unexpectedly at home). Five patients are alive five to 23 months after operation. Four are asymptomatic, and one has intermittent respiratory problems. The Waterston operation is a successful, palliative procedure in newborn infants with obstructive lesions of the right side of the heart who require a systemic-pulmonary arterial shunt for survival.
NK cells are dysfunctional in human chronic myelogenous leukemia before and on imatinib treatment and in BCR–ABL-positive mice
Authors: C I-U Chen, S Koschmieder, L Kerstiens, M Schemionek, B Altvater, S Pscherer, J Gerss, H T Maecker, W E Berdel, H Juergens, P P Lee, C Rossig
Journal: Leukemia (2011)
Development of a weak-base docetaxel derivative that can be loaded into lipid nanoparticles
Authors: Igor V Zhigaltsev, Geoff Winters, Masuna Srinivasulu, Jason Crawford, Matthew Wong, Lawrence Amankwa, Dawn Waterhouse, Dana Masin, Murray Webb, Natashia Harasym, Lindsay Heller, Marcel B Bally, Marco A Ciufolini, Pieter R Cullis, Norbert Maurer
Journal: Journal of Controlled Release (2010)
TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice
Authors: A. Toro, E. Grunebaum
Journal: Journal of Clinical Investigation (2006)

Defects in purine nucleoside phosphorylase (PNP) enzyme activity result in abnormal nucleoside homeostasis, severe T cell immunodeficiency, neurological dysfunction, and early death. Protein transduction domain (PTD) can transfer molecules into cells and may help restore PNP activity in cases of PNP deficiency. However, long-term use of PTD to replace enzymes in animal models or patients has not previously been described. We fused human PNP to the HIV-TAT PTD and found that the fusion with TAT changed the retention and distribution of PNP in PNP-deficient mice. TAT induced rapid intracellular delivery of PNP into tissues, including the brain, prevented urinary excretion of PNP, and protected PNP from neutralizing antibodies, resulting in significant extension of the enzyme's biological activity in vivo. Frequent TAT-PNP injections in PNP-deficient mice corrected the metabolic disorder and immune defects with no apparent toxicity. TAT-PNP remained effective over 24 weeks of treatment, resulting in continued improvement in immune function and extended survival. Our data demonstrate that TAT changes the properties of PNP in vivo and that long-term intracellular delivery of PNP by TAT corrects PNP deficiency in mice. We provide evidence to promote further use of PTD to treat diseases that require repeated intracellular enzyme or protein delivery.
Effects of antibiotic antitumor drugs on nucleotide levels in cultured tumor cells: an exploratory method to distinguish the mechanisms of antitumor drug action based on targeted metabolomics
Authors: Fang Wang, Xi Liu, Cuichai Liu, Zheng Liu, Lixin Sun
Journal: Acta Pharmaceutica Sinica B (2015)

Nucleotide pools in mammalian cells change due to the influence of antitumor drugs, which may help in evaluating the drug effect and understanding the mechanism of drug action. In this study, an ion-pair RP-HPLC method was used for a simple, sensitive and simultaneous determination of the levels of 12 nucleotides in mammalian cells treated with antibiotic antitumor drugs (daunorubicin, epirubicin and dactinomycin D). Through the use of this targeted metabolomics approach to find potential biomarkers, UTP and ATP were verified to be the most appropriate biomarkers. Moreover, a holistic statistical approach was put forward to develop a model which could distinguish 4 categories of drugs with different mechanisms of action. This model can be further validated by evaluating drugs with different mechanisms of action. This targeted metabolomics study may provide a novel approach to predict the mechanism of action of antitumor drugs.
The effects of agents that bind to cytochrome P-450 on hypoxic pulmonary vasoconstriction.
Authors: J T Sylvester, C McGowan
Journal: Circulation Research (1978)

The relationship between pulmonary arterial pressure (Ppa) and blood (Q) was determined during normoxia and hypoxia in ventilated pig lungs perfused in situ with the animal's own blood. Hypoxia shifted the Ppa-Q relationship to the right and decreased its slope, indicating pulmonary vasoconstriction. Carbon monoxide (11.5% in the inspired gas) and metyrapone ditartrate (10 mg/min into the perfusate) caused vasodilation when oxygenation was normal and reduced the vasoconstriction caused by hypoxia. Since the only pharmacological property CO and metyrapone are thought to have in common at the concentrations employed is the ability to bind to the heme iron of cytochrome P-450, these results are consistent with the hypothesis that desaturation of this cytochrome leads to pulmonary vasoconstriction. Prostaglandin F2alpha, infused into the pulmonary artery at 0.01 mg/min, when oxygenation was normal, had effects on the Ppa-Q relationship similar to those of hypoxia. The F2alpha response was also reduced by CO and metyrapone, suggesting either that P-450 was involved in the F2alpha response or that CO and metyrapone were toxic to pulmonary vascular smooth muscle. Proadifen hydrochloride (1 mg/min), which is thought to bind to the protein moiety of P-450 also reduced the hypoxic response, but was a vasoconstrictor during normoxia and did not affect the F2alpha response.
Aptiganel Hydrochloride in Acute Ischemic Stroke
Authors: Gregory W. Albers, Larry B. Goldstein, David Hall, Lynna M. Lesko, None for the Aptiganel Acute Stroke Investigators
Journal: JAMA (2001)

ContextTissue plasminogen activator is the only thrombolytic agent approved in the United States for treatment of acute ischemic stroke, and has limitations. Aptiganel hydrochloride is a novel and selective ligand for the ion-channel site of the N-methyl-D-aspartate receptor-channel complex and a promising neuroprotective agent in animal models of focal brain ischemia.ObjectiveTo determine whether aptiganel improves the clinical outcome for acute ischemic stroke patients.DesignNested phase 2/phase 3 randomized controlled trial conducted between July 1996 and September 1997.SettingOne hundred fifty-six medical centers in the United States, Canada, Australia, South Africa, England, and Scotland.ParticipantsA total of 628 patients with hemispheric ischemic stroke (50.3% male; mean age, 71.5 years).InterventionsPatients were randomly assigned within 6 hours of stroke to receive 1 of 3 treatment regimens: high-dose aptiganel (5-mg bolus followed by 0.75 mg/h for 12 hours; n = 214); low-dose aptiganel (3-mg bolus followed by 0.5 mg/h for 12 hours; n = 200); or placebo (n = 214).Main Outcome MeasuresThe primary efficacy end point was the Modified Rankin Scale score at 90 days after stroke onset. Secondary end points included mortality and change in National Institutes of Health (NIH) Stroke Scale score at 7 days after stroke.ResultsThe trial was suspended by the sponsor and the independent data and safety monitoring board because of both a lack of efficacy and a potential imbalance in mortality. There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P = .31). At 7 days, placebo-treated patients exhibited slightly greater neurological improvement on the NIH Stroke Scale than high-dose aptiganel patients (mean improvement for placebo group, −0.8 points vs for high-dose aptiganel, 0.9 points; P = .04). The mortality rate at 120 days in patients treated with high-dose aptiganel was higher than that in patients who received placebo (26.3% vs 19.2%; P = .06). Mortality in the low-dose aptiganel group was 22.5% (P = .39 vs placebo).ConclusionsAptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful. The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.