tbuckley/cabot-search huggingface dataset:
Wound-induced migration of rat hepatic stellate cells is modulated by endothelin-1 through rho-kinase-mediated alterations in the acto-myosin cytoskeleton
Authors: P Tangkijvanich
Journal: Hepatology (2001)

Although migration of stellate cells during hepatic injury is essential for wound-healing and fibrosis of the liver, the extracellular and intracellular signals that regulate stellate cell migration are incompletely understood. In this study we tested the hypothesis that wound-induced migration of stellate cells is modulated by endothelin-1 (ET-1) through rho-kinase-mediated alterations in the acto-myosin cytoskeleton. To address this hypothesis, a method was established for direct visualization of wound-induced migration of culture-activated stellate cells with subcellular resolution. Migration in response to wounding was characterized by (1) plasma membrane ruffling and protrusion into the wound, (2) lamellipodia formation at the leading edge, (3) focal adhesion and stress fiber assembly, and (4) myosin reorganization. Exogenous ET-1 accelerated wound-induced migration of stellate cells, but did not alter wound-induced proliferation. Experiments using ET-1 antagonists in the absence of exogenous ET-1 showed that wound-induced migration was also stimulated by endogenous ET-1. Selective inhibition of rho-associated kinase decelerated migration in response to wounding. Moreover, inhibition of rho-associated kinase was distinguished by abrogation of focal adhesion formation, stress fiber assembly, and myosin reorganization. This study shows that rho-kinase-dependent alterations in the acto-myosin cytoskeleton contribute to wound-induced stellate cell migration, which is accelerated by both exogenous and endogenous ET-1. Consequently, these results provide important new evidence suggesting that, migration of stellate cells is modulated by paracrine and autocrine ET-1 stimulation via the action of rho-kinase on the acto-myosin cytoskeleton.
The association between caries and childhood lead exposure.
Authors: J R Campbell, M E Moss, R F Raubertas
Journal: Environmental Health Perspectives (2000)

Epidemiologic studies suggest an association between lead exposure and caries. Our objective was to establish whether children with a higher lead exposure as toddlers had more caries at school age than children with a lower lead exposure. We used a retrospective cohort design. A sample of children who attended second and fifth grades in the Rochester, New York, public schools during the 1995-1996 and 1996-1997 school years were examined for caries through a dental screening program. For each child we assessed the number of decayed, missing, or filled surfaces on permanent teeth (DMFS), and the number of decayed or filled surfaces on deciduous teeth (dfs); the number of surfaces at risk (SAR) was also recorded. Lead exposure was defined as the mean of all blood lead levels collected between 18 and 37 months of age by fingerstick [provided the blood lead level was [less than/equal to] 10 microg/dL)] or venipuncture. A total of 248 children (197 second graders and 51 fifth graders) were examined for caries and had a record of blood lead levels to define lead exposure. The mean dfs was 3.4 (range 0-29); the mean DMFS was 0.5 (range 0-8). Logistic regression was used to examine the association between the proportion of children with DMFS [Greater/equal to] 1, and the proportion with dfs [Greater/equal to] 1, and lead exposure [&lt; 0.48 micromol/L vs. [Greater/equal to] 0.48 micromol/L (&lt; 10 microg/dL vs. [Greater/equal to] 10 microg/dL)] while controlling for SAR, age at examination, and grade in school. For DMFS, the adjusted odds ratio was 0.95 [95% confidence interval (CI), 0.43-2.09; p = 0.89); for dfs, the odds ratio was 1.77 (95% CI, 0.97-3.24; p = 0.07). This study did not demonstrate that lead exposure &gt; 10 microg/dL as a toddler was a strong predictor of caries among school-age children. However, the results should be interpreted cautiously because of limitations in the assessment of lead exposure and limited statistical power.
How should we decide on the best regimen for eradicating Helicobacter pylori?
Authors: V. Savarino, S. Vigneri
Journal: BMJ (1995)

hagen last March publicly criticised Premier Li Peng over this issue.In an effort to reduce the likelihood of similar disturbances in Beijing the Chinese moved the non-government organisations' women's forum, which is taking place at the same time as the UN conference, to Huairou, a rural location an hour away from Beijing.This move prompted furious reaction from the non-government organisations, not least because until recently Huairou had no hotels, few telephones or toilets, and no hall big enough to accommodate a conference of this size.The Chinese have promised to provide enough facilities, which include circus tents and hastily erected telephone lines.Shuttle buses will carry delegates and the press between the two sites.Despite the controversies the world conference has already succeeded in publicising many of the current inequalities.Women's health is inextricably linked with social conditions, and the platform for action acknowledges the link between health and many of the other critical areas of concern such as poverty, education, and human rights.The challenge is to agree a practical strategy in Beijing for social and cultural change that will reduce discrimination and empower future generations ofwomen.
Effect of inhaled frusemide on the early response to antigen and subsequent change in airway reactivity in atopic patients.
Authors: P Verdiani, S Di Carlo, A Baronti, S Bianco
Journal: Thorax (1990)

The purpose of this study was to investigate whether inhaled frusemide was able to inhibit the increase in nonspecific bronchial reactivity that occurs after the early response to allergen exposure in subjects with allergic rhinitis or asthma (or both). Ten symptom free patients initially underwent a challenge with methacholine, to determine the dose of methacholine that caused a 15% fall in FEV1 (PD15 FEV1 meth) and a challenge with a specific allergen, to determine the concentration of allergen that caused a fall in FEV1 of at least 15%. On two further occasions they inhaled allergen concentration that had caused the greater than or equal to 15% fall in FEV1 preceded by inhaled frusemide (40 mg frusemide in 4 ml buffered saline) or placebo (4 ml of diluent solution), according to a randomised, double blind, crossover design. All allergen studies were separated by at least seven days. A methacholine challenge was performed two hours after the allergen challenge, a time when the early response to allergen had completely resolved. Frusemide inhibited the early response to antigen, causing mean (95% confidence interval) protection of 87.6% (96-80%) for the maximum fall in FEV1. The increase in non-specific airway reactivity that occurred after antigen when this was preceded by placebo was reduced by frusemide. The mean (95% CI) difference in PD15 values between the placebo and the frusemide days was 1.73 (2.30-1.16) doubling doses of methacholine. These results confirm that frusemide is highly effective in preventing the early response to allergen, and show that it inhibits the increase in reactivity to methacholine that follows the early response.
Abstract 4717: Mobilization of Vascular Progenitor Cells in Patients Undergoing PCI Who Are Randomized to Receive Atorvastatin: Serial Assessment and Delineation of Timeline
Authors: Benjamin Hibbert, Ali Pourdjabbar, Xiaoli Ma, Erik Holm, Katey Rayner, Kevin Sun, Yong-Xiang Chen, Lionel Filion, Edward R O'Brien
Journal: Circulation (2009)
Sinusoidal endothelial cell repopulation following ischemia/reperfusion injury in rat liver transplantation
Authors: Donna Beer Stolz, Mark A. Ross, Atsushi Ikeda, Koji Tomiyama, Takashi Kaizu, David A. Geller, Noriko Murase
Journal: Hepatology (2007)

We evaluated the kinetics by which rat liver sinusoidal endothelial cells (LSECs) are repopulated in the reperfused transplanted liver after 18 hours of cold ischemic storage. We found that the majority of LSECs in livers cold-stored for 18 hours in University of Wisconsin solution are seriously compromised and often are retracted before transplantation. Sinusoids rapidly re-endothelialize within 48 hours of transplantation, and repopulation is coincident with up-regulation of hepatocyte vascular endothelial growth factor expression and vascular endothelial growth factor receptor-2 expression on large vessel endothelial cells and repopulating LSECs. Although re-endothelialization occurs rapidly, we show here, using several high-resolution imaging techniques and 2 different rat liver transplantation models, that engraftment of bone marrow–derived cells into functioning LSECs is routinely between 1% and 5%. Conclusion: Bone marrow plays a measurable but surprisingly limited role in the rapid repopulation and functional engraftment of bone marrow–derived LSECs after cold ischemia and warm reperfusion.
Abstract 5533: Novel targets and monoclonal antibodies for cancer therapy.
Authors: Alberto Grandi, Matteo Parri, Susanna Campagnoli, Renzo Nogarotto, Elisa De Camilli, Ilaria Naldi, Caterina Cinti, Paolo Sarmientos, Guido Grandi, Luigi Terracciano, Giuseppe Viale, Piero Pileri, Renata Maria Grifantini
Journal: Cancer Research (2013)

Abstract Cancer therapeutic targets is an extremely active research field in both academia and pharmaceutical companies. In our recent research activities we identified by a high-throughput immunohistochemistry screening of Tissue microarray (TMA), a panel of 89 novel candidate tumor markers for prevalent cancers representing breast, lung colon ovary and prostate carcinomas. The novel marker candidates were found over-expressed in one or more of the five tumors under analysis, with significant frequency. Three of them seems to be promising therapeutic targets for monoclonal antibody therapy, being exposed on the surface of cancer cells. They include: 1) a lectin binding protein, over-expressed in breast, lung and ovary cancer; 2) a protein involved in iron homoeostasis and over-expressed in breast, colon, lung and ovary cancers, 3) a cadherin homologous protein detected in colon, lung and ovary cancers. Gene silencing using siRNA technology and/or over-expression experiments using marker-encoding plasmids significantly alter cell proliferation, migration, invasiveness and clonal growth in vitro, indicating that expression of the three proteins confers cell phenotypes relevant for tumor progression. Highly specific murine monoclonal antibodies (mAbs) were generated against the three proteins and proved to bind the surface of cancer cells lines. Of particular interest is a murine mAb targeting the cadherin-like protein that, upon binding to the cell surface, is efficiently internalized by cancer cells, suggesting that it is amenable to the development of antibody-drug conjugates. This mAb did not show any relevant IHC cross-reactivity in the 35 human tissues requested by FDA to demonstrate antibody specificity. Furthermore this mAb significantly inhibited tumor growth in athymic nude mice bearing HCT15 and HT29 colon cancer xenograft models. Finally, IHC analysis of approximately 300 colon cancer clinical samples indicates that the antibody stains a large fraction of colon cancer samples, and gives intense membranous staining in specific patients’ group. Overall, data indicate that this antibody could be developed as a novel tool for a targeted therapy of colo-rectal cancer, alone or in combination with other treatments Citation Format: Alberto Grandi, Matteo Parri, Susanna Campagnoli, Renzo Nogarotto, Elisa De Camilli, Ilaria Naldi, Caterina Cinti, Paolo Sarmientos, Guido Grandi, Luigi Terracciano, Giuseppe Viale, Piero Pileri, Renata Maria Grifantini. Novel targets and monoclonal antibodies for cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5533. doi:10.1158/1538-7445.AM2013-5533
Cardiac Size and Left Ventricular Performance
Authors: Paul D. Stein
Journal: JAMA (1974)

The validity of using the measurement of the cardiac silhouette as an objective guide for the evaluation of left ventricular performance was investigated in 75 patients with arteriographically demonstrated coronary heart disease. None of the measurements of the silhouette, when normal, reliably excluded poor left ventricular function. Even the most reliable dimensions of the cardiac silhouette, the frontal plane transverse diameter, oblique diameter, and cardiothoracic ratio, frequently were normal in individuals with moderate to severe impairment of ventricular function. The results of this study suggest that the size of the cardiac silhouette should be considered only secondarily for the purpose of clinically evaluating the functional state of the left ventricle. By implication, these results also suggest that a greater reliance should be placed on other clinical methods, including a carefully taken history and physical examination. (<i>JAMA</i>229:1614-1620, 1974)
Standardization of the Phenolsulfonphthalein Excretion Test in Clinical Practice
Authors: James M. Pierce
Journal: JAMA (1961)

THE15-minute phenolsulfonphthalein (PSP) excretion test is a widely used clinical test of renal function. Fifteen minutes after the intravenous injection of 6 mg. of phenolsulfonphthalein the patient empties his bladder, and the amount of dye excreted in the urine specimen is determined and expressed as a percentage of that injected. The excretion of 25 per cent of the injected dye within 15 minutes is generally considered to be the lower limit of normal renal function.<sup>1</sup>The 15-minute post-injection urine sample has generally been considered to be the ideal standard, since, in longer periods of time, even poorly functioning kidneys will be able to excrete a good percentage of the injected dye. Frequently, under office and hospital conditions it is impossible to obtain an exactly timed 15-minute urine specimen. This may be due to neglect of the examiner to make the collection or to inability of the patient to
Abstract 2595: Predictive value tools as an aid in chemopreventive agent development.
Authors: Barbara K. Dunn, Vernon E. Steele, Richard M. Fagerstrom, Carol F. Topp, David Ransohoff, Christopher Cunningham, Ronald A. Lubet, Leslie G. Ford, Barnett S. Kramer
Journal: Cancer Research (2013)

Abstract Over the past 25 years the Chemoprevention Agent Development Research Group of the Division of Cancer Prevention in the NCI has entered approximately 800 agents into a program designed to test for cancer preventive efficacy. The first 2 key steps in the testing pathway are in vitro/in vitro morphologic assays and, for agents successful in these, anti-tumor testing (tumor incidence and multiplicity reduction) in animal tumor models. Ultimately, agents that successfully decrease tumor incidence and multiplicity in animal models could progress to testing in humans. The goal of the current project is to evaluate the success of our program by determining how accurately the earlier stage assays (morphologic assays) predict efficacy in the later-stage assays (animal tumor assays). In our approach the 208 agents that were tested in both morphologic and animal tumor assays in this program were included in our analysis. Statistical modeling of the input from the 6 most commonly used morphologic assays into predicting the efficacy of agents in animal tumor models was carried out by multimodel inference. The statistical models that were generated predicted the ability of these 6 morphologic assays to predict tumor outcomes in animal models representing (1) all tumor types, (2) breast cancer only, and (3) colon cancer only. The statistical models assigned each morphologic assay a value describing how strongly it predicted outcomes in each of the 3 animal tumor assay settings. The development of these predictive models will guide our future decision-making with respect to agent selection as well as morphologic and animal tumor assay use. Our goal is to improve the efficiency of the overall process of chemoprevention agent development. Citation Format: Barbara K. Dunn, Vernon E. Steele, Richard M. Fagerstrom, Carol F. Topp, David Ransohoff, Christopher Cunningham, Ronald A. Lubet, Leslie G. Ford, Barnett S. Kramer. Predictive value tools as an aid in chemopreventive agent development. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2595. doi:10.1158/1538-7445.AM2013-2595
Intravenous Dofetilide, a Class III Antiarrhythmic Agent, for the Termination of Sustained Atrial Fibrillation or Flutter
Authors: Rodney H. Falk, Arthur Pollak, Steven N. Singh, Tilman Friedrich
Journal: Journal of the American College of Cardiology (1997)

Objectives. This study sought to determine the safety and efficacy of a single bolus of intravenous dofetilide, a pure class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. Background. Dofetilide is a highly selective blocker of the rapid component of the delayed rectifier current causing action potential prolongation. These effects, and preliminary clinical data, suggest that it may be effective in the treatment of atrial fibrillation and flutter. Methods. Ninety-one patients with sustained atrial fibrillation (75 patients) or flutter (16 patients) were entered into a double-blind, randomized multicenter study of one of two doses of dofetilide (4 or 8 μg/kg body weight) or placebo. Results. Dofetilide effectively terminated the arrhythmia in 31% of patients receiving 8 μg/kg, a statistically significant difference from those receiving 4 μg/kg (conversion rate 12.5%, p < 0.05) or placebo (no conversion, p < 0.01). Patients with atrial flutter had a greater response to dofetilide (54% conversion rate) than those with atrial fibrillation (14.5% conversion rate, p < 0.001). Conclusions. Intravenous dofetilide can convert sustained atrial fibrillation or flutter to sinus rhythm. However, its efficacy is greater in flutter—a response that contrasts with the poorer response seen with class I agents. This finding potentially represents an important advance in the pharmacologic termination of atrial flutter. (J Am Coll Cardiol 1997;29:385–90)
Value of knee imaging by GPs requires rigorous assessment
Authors: S. Brealey
Journal: BMJ (2002)

EDITOR—In his editorial McNally reports that magnetic resonance imaging has had a great effect on the management of internal derangement of the knee and is increasingly available to hospital specialists and general practitioners.1 Whether general practitioners' access to imaging has as great an effect as use by a knee specialist, however, is not known.2 This question is crucial to patient management and outcome, and thus to cost effectiveness.

Access to magnetic resonance imaging by general practitioners for patients with …
If Arteries and Veins Were People
Authors: ORVILLE HORWITZ
Journal: Annals of Internal Medicine (1962)

Editorials1 April 1962If Arteries and Veins Were PeopleORVILLE HORWITZ, M.D., F.A.C.P.ORVILLE HORWITZ, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-663 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the process of reviewing the history of a patient who had occlusion of the superior vena cava, it recurred to me how very differently arteries and veins react to insults that are thrust upon them. They are both necessary to mammalian life, both involved in the business of transporting blood; but there the similarity stops. The small differences in their duties seem to have converted them into entirely different personalities.On the whole arteries are conservative, uncompromising, unimaginative, thick, muscular, pyknic, valveless, inconsiderate, respected, and for the most part honest and popular; whereas veins are wild, liberal, compromising, imaginative,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ORVILLE HORWITZ, M.D., F.A.C.P.Affiliations: Hospital of the University of Pennsylvania 3400 Spruce Street Philadelphia 4, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 663-664KeywordsArteriesBloodPersonalityVeins ePublished: 1 December 2008 Issue Published: 1 April 1962 PDF downloadLoading ...
<i>In Utero</i> and Lactational Exposure to PCBs in Mice: Adult Offspring Show Altered Learning and Memory Depending on <i>Cyp1a2</i> and <i>Ahr</i> Genotypes
Authors: Christine P. Curran, Daniel W. Nebert, Mary Beth Genter, Krishna V. Patel, Tori L. Schaefer, Matthew R. Skelton, Michael T. Williams, Charles V. Vorhees
Journal: Environmental Health Perspectives (2011)

Background: Both coplanar and noncoplanar polychlorinated biphenyls (PCBs) exhibit neurotoxic effects in animal studies, but individual congeners do not always produce the same effects as PCB mixtures. Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; because CYP1A2 is known to sequester coplanar PCBs and because AHR ligands include coplanar PCBs, both genotypes can affect PCB response.Objectives: We aimed to develop a mouse paradigm with extremes in Cyp1a2 and Ahr genotypes to explore genetic susceptibility to PCB-induced developmental neurotoxicity using an environmentally relevant mixture of PCBs.Methods: We developed a mixture of eight PCBs to simulate human exposures based on their reported concentrations in human tissue, breast milk, and food supply. We previously characterized specific differences in PCB congener pharmacokinetics and toxicity, comparing high-affinity–AHR Cyp1a2 wild-type [Ahrb1_Cyp1a2(+/+)], poor-affinity–AHR Cyp1a2 wild-type [Ahrd_Cyp1a2(+/+)], and high-affinity–AHR Cyp1a2 knockout [Ahrb1_Cyp1a2(–/–)] mouse lines [Curran CP, Vorhees CV, Williams MT, Genter MB, Miller ML, Nebert DW. 2011. In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes. Toxicol Sci 119:189–208]. Dams received a mixture of three coplanar and five noncoplanar PCBs on gestational day 10.5 and postnatal day (PND) 5. In the present study we conducted behavioral phenotyping of exposed offspring at PND60, examining multiple measures of learning, memory, and other behaviors.Results: We observed the most significant deficits in response to PCB treatment in Ahrb1_Cyp1a2(–/–) mice, including impaired novel object recognition and increased failure rate in the Morris water maze. However, all PCB-treated genotypes showed significant differences on at least one measure of learning or behavior.Conclusions: High levels of maternal hepatic CYP1A2 offer the most important protection against deficits in learning and memory in offspring exposed to a mixture of coplanar and noncoplanar PCBs. High-affinity AHR is the next most important factor in protection of offspring.