tbuckley/cabot-search huggingface dataset:
Novel Role of ARF6 in Vascular Endothelial Growth Factor–Induced Signaling and Angiogenesis
Authors: Satoshi Ikeda, Masuko Ushio-Fukai, Lian Zuo, Taiki Tojo, Sergey Dikalov, Nikolay A. Patrushev, R. Wayne Alexander
Journal: Circulation Research (2005)

Vascular endothelial growth factor (VEGF) stimulates endothelial cell (EC) migration and proliferation primarily through the VEGF receptor-2 (VEGFR2). We have shown that VEGF stimulates a Rac1-dependent NAD(P)H oxidase to produce reactive oxygen species (ROS) that are involved in VEGFR2 autophosphorylation and angiogenic-related responses in ECs. The small GTPase ARF6 is involved in membrane trafficking and cell motility; however, its roles in VEGF signaling and physiological responses in ECs are unknown. In this study, we show that overexpression of dominant-negative ARF6 [ARF6(T27N)] almost completely inhibits VEGF-induced Rac1 activation, ROS production, and VEGFR2 autophosphorylation in ECs. Fractionation of caveolae/lipid raft membranes demonstrates that ARF6, Rac1, and VEGFR2 are localized in caveolin-enriched fractions basally. VEGF stimulation results in the release of VEGFR2 from caveolae/lipid rafts and caveolin-1 without affecting localization of ARF6, Rac1, or caveolin-1 in these fractions. The egress of VEGFR2 from caveolae/lipid rafts is contemporaneous with the tyrosine phosphorylation of caveolin-1 (Tyr14) and VEGFR2 and with their association with each other. ARF6(T27N) significantly inhibits both VEGF-induced responses. Immunofluorescence studies show that activated VEGFR2 and phosphocaveolin colocalize at focal complexes/adhesions after VEGF stimulation. Both overexpression of ARF6(T27N) and mutant caveolin-1(Y14F), which cannot be phosphorylated, block VEGF-stimulated EC migration and proliferation. Moreover, ARF6 expression is markedly upregulated in association with an increase in capillary density in a mouse hindlimb ischemia model of angiogenesis. Thus, ARF6 is involved in the temporal-spatial organization of caveolae/lipid rafts- and ROS-dependent VEGF signaling in ECs as well as in angiogenesis in vivo.
When the Side Effect Helps the Treatment: Graft-versus-Tumor
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article When the Side Effect Helps the Treatment: Graft-versus-Tumor Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 11, 2 June 1993, Pages 855–856, https://doi.org/10.1093/jnci/85.11.855 Published: 02 June 1993
A PROSTATIC BAG
Authors: Tom R. Barry
Journal: JAMA (1926)

Various devices to control bleeding after prostatectomy have been described. Many of these are bulky, very painful to remove and are not always available. The chief objections to the use of the Hagner and Pilcher bags are, (1) the necessity of withdrawing the end through the urethra and bladder and out the suprapubic wound, which is extremely painful, difficult and not always aseptic; and (2) the necessity of removing and again replacing the suprapubic drain. I have used the following simple modification of the Hagner bag with entirely satisfactory results: The bag consists of a soft rubber catheter 22 F., and a three-eighth inch cigaret drainage tubing, 7 inches long. The tubing is telescoped, making a double thickness 3½ inches long. One end is tied off with silk, and the double is then inverted so that the end will be inside the bag when it is inflated. The catheter is
Multiple Efforts Directed at Defining, Eliminating Excess Radiation
Authors: Beverly Merz
Journal: JAMA (1987)

THE FIRST MAJOR REPORT on the adverse health effects of ionizing radiation appeared inThe Journal62 years ago (<i>JAMA</i>1925;85:1769-1776). It was entitled "Some Unrecognized Dangers in the Use of and the Handling of Radioactive Substances." The "dangers" were severe illness and death. The report, written by Harrison S. Martland, MD, Philip Conlon, MD, and Joseph P. Knef, DDS, summarized a series of events that began with the use of roentgen rays and radioactive substances in medicine and industry at the turn of the century. It noted cases of radium-induced burns and dermatitis in chemists; mentioned reports of the deaths from aplastic anemia and cancer among radiologists; and identified osteomyelitis of the mandible as an occupation-related disorder among workers in luminous dial factories. The investigators also noted that expired air from dial painters with osteomyelitis and anemia was radioactive, as was bone, spleen, and liver tissue taken from a
Health Warnings, Smoking, and Cancer
Authors: George J. Annas
Journal: New England Journal of Medicine (1992)

The figures have become familiar. Tobacco use has been declared "the single most important preventable cause of [premature] death in the United States, accounting for one of every six deaths, or some 390,000 deaths annually."1 The health goals of the nation for the year 2000 call for reducing the prevalence of cigarette smoking to 15 percent among adults (a 48 percent decrease from the current 29 percent) and reducing the rate of beginning smoking among teenagers to 15 percent (a 50 percent decrease from the current rate of 30 percent).2 The goal of reducing smoking in the United States is . . .
Soil is an important pathway of human lead exposure.
Authors: H W Mielke, P L Reagan
Journal: Environmental Health Perspectives (1998)

This review shows the equal or greater importance of leaded gasoline-contaminated dust compared to lead-based paint to the child lead problem, and that soil lead, resulting from leaded gasoline and pulverized lead-based paint, is at least or more important than lead-based paint (intact and not pulverized) as a pathway of human lead exposure. Because lead-based paint is a high-dose source, the biologically relevant dosage is similar to lead in soil. Both lead-based paint and soil lead are associated with severe lead poisoning. Leaded gasoline and lead in food, but not lead-based paint, are strongly associated with population blood lead levels in both young children and adults. Soil lead and house dust, but not lead-based paint, are associated with population blood lead levels in children. Most soil lead and house dust are associated with leaded gasoline. Lead-based paint dust is associated with cases of renovation of either exterior or interior environments in which the paint was pulverized. Based upon the limited data to date, abatement of soil lead is more effective than abatement of lead-based paint in reducing blood lead levels of young children. About equal numbers of children under 7 years of age are exposed to soil lead and lead-based paint. Seasonality studies point to soil lead as the main source of population blood lead levels. Soil lead is a greater risk factor than lead-based paint to children engaged in hand-to-mouth and pica behavior. In summary, soil lead is important for addressing the population of children at risk of lead poisoning. When soil lead is acknowledged by regulators and the public health community as an important pathway of human lead exposure, then more effective opportunities for improving primary lead prevention can become a reality.
A model standardized risk assessment protocol for use with hazardous waste sites.
Authors: G M Marsh, R Day
Journal: Environmental Health Perspectives (1991)

This paper presents a model standardized risk assessment protocol (SRAP) for use with hazardous waste sites. The proposed SRAP focuses on the degree and patterns of evidence that exist for a significant risk to human populations from exposure to a hazardous waste site. The SRAP was designed with at least four specific goals in mind: to organize the available scientific data on a specific site and to highlight important gaps in this knowledge; to facilitate rational, cost-effective decision making about the best distribution of available manpower and resources; to systematically classify sites roughly according to the level of risk they pose to surrounding human populations; and to promote an improved level of communication among professionals working in the area of waste site management and between decision makers and the local population.
The Effect of Cell Division on the Cellular Dynamics of Microinjected DNA and Dextran
Authors: James J. Ludtke, Magdolna G. Sebestyén, Jon A. Wolff
Journal: Molecular Therapy (2002)

Gene delivery is a multistep process that is being studied to increase its efficiency, a major hurdle for effective gene therapy. Our study focused on the nuclear entry step by microinjecting a mixture of fluorescent dextran and the pEYFP-Nuc plasmid (encoding a nuclear-targeted, enhanced GFP) into the cytoplasm of nondividing and dividing cells that were selected using non-chemical means. After 10 and 1000 ng/microl of plasmid DNA (pDNA) were cytoplasmically injected, 28% and 50% of the cells that had not divided expressed GFP, respectively, compared with 50% and 90% for the cells that had divided. This result suggested that pDNA can enter the nonmitotic nuclei of mononucleated cells, albeit at a lower efficiency than mitotic nuclei. The ability of pDNA to enter the intact nuclei of nondividing cells is consistent with our previous experience using multinucleated myotubes and digitonin-permeabilized cells in culture and using intravascular naked pDNA delivery in vivo. An explanation for the small effect of cell division was provided by studies using fluorescently labeled molecules and confocal fluorescent microscopy. They showed that the bulk of large dextran, and similarly pDNA, was excluded from re-formed nuclei after mitosis, thereby limiting the effect of cell division on the nuclear entry of pDNA.
A139: Body Mass Index and Height Change Over Time in Childhood-Onset Systemic Lupus Erythematosus Cohort
Authors: Julia G. Harris, Kristyn I. Maletta, Evelyn M. Kuhn, Judyann C. Olson
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

Systemic lupus erythematosus (SLE) can lead to significant morbidity and mortality related to coronary artery disease. Obesity is an additional risk factor for cardiovascular disease that appears to be more prevalent in this population. Obesity in SLE has been linked to decreased health-related quality of life, functional limitations, pain, fatigue, diabetes mellitus, and increased malignancies. In addition, growth retardation is an important aspect to consider in a child or adolescent that is exposed to corticosteroids. Growth failure has been a proposed addition to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) to modify this validated scale for childhood-onset SLE (cSLE). There is limited data discussing change in growth parameters over time in cSLE patients, which our study sought to do.



Methods:

A retrospective chart review was performed on patients diagnosed with SLE prior to age 18 who were followed in the Children's Hospital of Wisconsin Rheumatology Clinic for at least one year between January 1999 and August 2012. Weight and height were collected two times per year. Body mass index (BMI; kg/m2) and percentiles of measurements for age were calculated based on sex-specific growth references from the Centers for Disease Control and Prevention for patients 2 to 20 years old. Additional information collected included age of diagnosis, medication use, presence of lupus nephritis, and items of disease damage based on the SDI.



Results:

Analysis was performed on 75 patients with mean disease duration of 4.55 years. There were 685 growth for age percentile values recorded. Mean BMI percentage per age at diagnosis was 64.81 compared to 76.31 at the 610 follow-up visits, which was statistically significant (p < 0.001). At diagnosis, 33.3% of patients were overweight (≥85–95% BMI for age), obese (≥95–99% BMI for age), or severely obese (≥99% BMI for age) versus 49.3% at last available follow-up visit. Sixty-eight percent of patients had at least one BMI measurement out of the normal range. Mean percent height for age at diagnosis was 64.21 versus 46.58 at follow-up visits (p < 0.001). Eight of the seventy-five patients had growth percentiles <5% at last follow-up visit. 



Conclusion:

A majority of our cSLE population was overweight or obese during at least one time period. In addition, BMI statistically increased from diagnosis to follow-up visits. Growth failure was present in greater than 10% of the population, and percent height for age statistically decreased after diagnosis as well. Interventions related to healthy living habits and medication adjustments should be made to address these important growth issues that can have long-standing complications.
Protection of Zinc against Tumor Necrosis Factor–Induced Lethal Inflammation Depends on Heat Shock Protein 70 and Allows Safe Antitumor Therapy
Authors: Wim Van Molle, Maarten Van Roy, Tom Van Bogaert, Lien Dejager, Philippe Van Lint, Ineke Vanlaere, Kenji Sekikawa, George Kollias, Claude Libert
Journal: Cancer Research (2007)

Abstract Tumor necrosis factor (TNF)–induced inflammation prevents its broad application as an antitumor agent. We here report that addition of ZnSO4 to the drinking water of mice induces expression of heat shock protein 70 (HSP70) in several organs, notably the gastrointestinal track. Zinc conferred dose-responsive protection against TNF-induced hypothermia, systemic induction of interleukin-6 and NOx, as well as against TNF-induced bowel cell death and death of the organism. The protective effect of zinc was completely absent in mice deficient in the major HSP70-inducible gene, hsp70.1, whereas transgenic mice constitutively expressing the human HSP70.A gene, under control of a β-actin promoter, was also protected against TNF, indicating that an increase in HSP70 is necessary and sufficient to confer protection. The therapeutic potential of the protection induced by ZnSO4 was clearly shown in a TNF/IFNγ–based antitumor therapy using three different tumor models. In hsp70.1 wild-type mice, but not in hsp70.1-deficient mice, zinc very significantly protected against lethality but left the antitumor effect intact. We conclude that zinc protects against TNF in a HSP70-dependent way and that protection by zinc could be helpful in developing a safer anticancer therapy with TNF/IFNγ. [Cancer Res 2007;67(15):7301–7]
Impact of targeted therapy on outcome of chronic lymphocytic leukemia patients with relapsed del(17p13.1) karyotype at a single center
Authors: D M Stephens, A S Ruppert, J A Jones, J Woyach, K Maddocks, S M Jaglowski, L A Andritsos, J M Flynn, M R Grever, G Lozanski, A J Johnson, N Muthusamy, N A Heerema, J C Byrd
Journal: Leukemia (2014)
Hepatoma Associated with Hypoglycemia, Polycythemia, and Hypercalcemia
Authors: David J. Becker, Martin S. Sternberg, Martin H. Kaiser
Journal: JAMA (1963)

NUMEROUS SYNDROMES reflecting altered metabolism have been described in association with primary neoplastic disease.<sup>1</sup>The following case tells of a patient in whom primary carcinoma of the liver was associated with polycythemia, hypercalcemia, and profound hypoglycemia. Although the polycythemia and hypercalcemia were laboratory curiosities, the hypoglycemia resulted in recurrent syncope and ultimately determined the patient's clinical picture and the attendant problems of management. Spontaneous hypoglycemia and polycythemia have been reported separately in patients with hepatomas.<sup>2-7</sup>The association of the three has been recorded once by Schonfeld et al.<sup>8</sup>The additional findings of hypercalcemia in the current case of hepatoma is a previously unreported association. <h3>Report of a Case</h3> A 36-year-old Negro male died after a 7-month illness characterized by anorexia, fatigue, and weight loss in association with increasing hepatomegaly. There were no historical data to suggest nutritional, toxic, or infectious liver disease. Three months prior to death,
mRNA-Lipoplex loaded microbubble contrast agents for ultrasound-assisted transfection of dendritic cells
Authors: Marie-Luce De Temmerman, Heleen Dewitte, Roosmarijn E. Vandenbroucke, Bart Lucas, Claude Libert, Jo Demeester, Stefaan C. De Smedt, Ine Lentacker, Joanna Rejman
Journal: Biomaterials (2011)
Skin application of the nonsteroidal anti-inflammatory drug ketoprofen downmodulates the antigen-presenting ability of Langerhans cells in mice
Authors: K. Atarashi, K. Kabashima, K. Akiyama, Y. Tokura
Journal: British Journal of Dermatology (2008)

Ketoprofen (KP) is widely used as a topical nonsteroidal anti-inflammatory drug that inhibits prostaglandin (PG) biosynthesis. As PGE(2) upregulates the antigen-presenting activity of Langerhans cells (LCs), i.e. migration to lymph nodes and expression of immunocompetent molecules, modulation of LC functions resulting from topical application of KP is an issue to be clarified.To investigate the in vivo effect of KP application to the skin and the in vitro effect of KP addition to the culture on the antigen-presenting ability of murine LCs. Methods Ears of BALB/c mice were painted with picryl chloride (PCl) hapten, KP or both. An immunofluorescence study of epidermal sheets and a flow cytometric analysis of epidermal cell suspensions from the treated ears were performed.PCl altered the morphology of LCs and reduced their number, and simultaneous application of 10% KP maintained LC morphology and number. KP at 5% or 10% clearly decreased the PCl-augmented expression of major histocompatibility complex class II and CD86 on LCs. In cultivation of freshly isolated epidermal cells, 5 mmol L(-1) KP inhibited the culture-promoted expression of these molecules on LCs, whereas 100 micromol L(-1) indomethacin was not inhibitory. The further addition of PGE(2) to the KP-containing epidermal cell culture did not restore the expression of these molecules. Moreover, topical application of 10% KP to the sensitizing sites suppressed the development of contact hypersensitivity to PCl.KP may have the potential to inhibit the antigen-presenting ability of LCs, in a PGE(2)-independent manner.
Manipulating Nature
Authors: David S. Celermajer
Journal: Circulation (2012)

A ssisted reproductive technologies (ARTs) have brought the miracle of childbirth to literally hundreds of thousands of adults who would otherwise not have conceived children; indeed, it is now estimated that 1% to 3% of all births in many developed nations involve ARTs. 1 The first ART birth, however, was not until 1978, and so even the oldest such offspring are only now entering young adult life.Will they have the same health outcomes as those babies conceived "naturally"?
A vital clue to deciphering bone pathology: MRI bone oedema in rheumatoid arthritis and osteoarthritis
Authors: F M McQueen
Journal: Annals of the Rheumatic Diseases (2007)

In summary, MRI bone oedema is an important finding in RA and OA. Points of similarity and difference are listed in table 1​1.. In RA, evidence from the imaging modality itself (increased signal postcontrast indicating vascularity) and from limited histopathological studies suggests that bone oedema represents an inflammatory cellular infiltrate within the subchondral bone. It certainly behaves as such in response to biological disease‐modifying antirheumatic drugs and could be more sensitive than synovitis as a marker of therapeutic response.21 It also predicts radiographic erosive progression and could be regarded as the “missing link” between joint inflammation and damage. In OA, bone oedema is similar in being strongly associated with pain but different in that it is probably not primarily an inflammatory lesion. The pain of OA bone oedema could be due to stimulation of the richly innervated periosteum by mediators released from necrotic tissue, to trabecular microfractures or to a pressure effect from abnormal tissue invading regions that should contain fat alone, as occurs in leukaemic infiltration.35 Histological studies have revealed fibrosis and trabecular thickening, to the point that bone density can be increased. This would fit with a process of bone remodelling and fibrosis leading on to joint damage with radiographic progression. Clearly, the subchondral bone is not “inert” in OA any more than it is in RA, and while bone oedema may be a different lesion histologically in these conditions, it is a red flag in both for progressive bone damage and potentially an important biomarker for use in clinical trials.



Table 1 Bone oedema in RA and OA




Acknowledgements

The author is indebted to Dr David Perry for assisting with preparation of images used in fig 1.
The effect of pericardiectomy on maximal oxygen consumption and maximal cardiac output in untrained dogs.
Authors: J Stray-Gundersen, T I Musch, G C Haidet, D P Swain, G A Ordway, J H Mitchell
Journal: Circulation Research (1986)

To test the hypothesis that the pericardium limits maximal oxygen consumption by limiting stroke volume and cardiac output, we studied 10 untrained dogs during submaximal and maximal exercise before and after pericardiectomy. Seven additional dogs were studied before and after a sham operation. All dogs were instrumented chronically with aortic and pulmonary artery catheters. Dogs were tested by running on a motor-driven treadmill, 4-6 times before and after pericardiectomy or sham operation. We measured cardiac output (dye dilution), heart rate, and arteriovenous oxygen difference. Oxygen consumption and stroke volume were calculated from these variables. After pericardiectomy, there were significant (P less than 0.01) increases in maximal oxygen consumption, maximal cardiac output, and maximal stroke volume. Maximal oxygen consumption decreased significantly in the sham group. There was no change in maximal heart rate following pericardiectomy, or in maximal cardiac output, heart rate, or stroke volume following sham operation. Both groups of dogs experienced similar significant decreases in hematocrit, arterial and venous oxygen contents, and arteriovenous oxygen difference. Neither pericardiectomy nor sham operation had any effect on oxygen consumption during submaximal exercise. However, the sham group had significant increases in cardiac output and heart rate during submaximal exercise, and the pericardiectomy group demonstrated a trend toward an increased cardiac output during submaximal exercise. These results support the hypothesis that the pericardium limits maximal oxygen consumption by limiting stroke volume and cardiac output during maximal exercise in untrained dogs. Further, these findings suggest that maximal oxygen consumption is limited by the oxygen transport capacity of the cardiovascular system, and not by the oxidative capacity of skeletal muscle in the untrained dog.
Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1+/−p53−/− mice
Authors: Justyna T. Romer, Hiromichi Kimura, Susan Magdaleno, Ken Sasai, Christine Fuller, Helen Baines, Michele Connelly, Clinton F. Stewart, Stephen Gould, Lee L. Rubin, Tom Curran
Journal: Cancer Cell (2004)