tbuckley/cabot-search huggingface dataset:
45. Paclitaxel-TRAIL Enhances the Distribution of Oncolytic Herpes Simplex Virus-1 in a Human Mammary Carcinoma Xenograft
Authors: Satoshi Nagano, Jean Y. Perentes, Rakesh K. Jain, Yves Boucher
Journal: Molecular Therapy (2006)

Oncolytic gene therapy has been shown to work synergistically with chemotherapy or radiation. On the other hand, for successful eradication of the tumor by oncolytic gene therapy initial widespread distribution of the virus within the tumor is crucial. However, viral distribution in the tumor is limited by the large size of viral vectors, which limits their penetration and distribution through the fine interstices of the interstitial matrix (IM) and the narrow spaces separating tumor cells. To by-pass these tissue barriers, we tested if the larger void spaces (poor in IM content) induced by tumor cell apoptosis enhance the distribution of oncolytic herpes simplex virus (HSV) in tumors. In vitro, breast cancer cells (MCF-7, MCF-7-W9, MDA-MB-435S and MDA-MB-231) were treated with paclitaxel (100 nM), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, 100 mM) or paclitaxel (100 nM) plus TRAIL (100 mM). Apoptosis was measured with a DNA fragmentation assay. Paclitaxel plus TRAIL induced significantly higher levels of apoptosis than treatment with paclitaxel or TRAIL alone. TRAIL induced apoptosis was caspase-8 dependent. In vivo, mice with MDA-MB-435S mammary fat pad tumors were treated with saline or paclitaxel (15 mg/Kg) plus TRAIL (500 μg/mouse). Tumor apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and cleaved caspase-3 staining. There was a significantly higher percentage of apoptosis in tumors treated with paclitaxel plus TRAIL. To test the effect of apoptosis on the distribution of oncolytic HSV expressing the green fluorescent protein (GFP), HSV was injected intratumorally following pre-treatments with saline or paclitaxel plus TRAIL. The fractional tumor volume expressing the GFP transgene was determined in tumor sections. Forty-eight hours after HSV, pre- treatment with paclitaxel plus TRAIL significantly increased the tumor distribution of HSV by 2.2 fold as compared to control tumors. In both the control and paclitaxel-TRAIL treated tumors there was less GFP expression in the periphery than in the center of tumors. We have recently shown that fibrillar collagen in tumors limits the distribution of HSV, we thus stained sections with a collagen I antibody. The collagen network was very dense in the tumor periphery, whereas in the tumor center there was less collagen-1 staining. The high collagen density in the tumor periphery may limit the access of the virus. In conclusion paclitaxel plus TRAIL-induced apoptosis enhances the distribution of oncolytic HSV in MDA-MB-435S tumors.
Moving ahead--community care in Gwent.
Authors: R Robinson
Journal: BMJ (1993)

competition (as presumably in the case of research council or charitable awards) this is a proper unassail- able token of merit.The same cannot be said of the other posts listed in table I, where vigorous protective mechanisms appear to have been at work.What has happened hitherto is evident from a broader picture-the distribution of all medical staff between London and the regions.Some change in the ratio between London (including undergraduate and postgraduate hospitals) has occurred over the past decade, but this is wholly attributable to a more rapid increase in numbers of medical staff in the provinces: levels increased at both sites.The pattern has not therefore been one of redistribution-merely differen- tial growth (table II).TABLE II-Average numbers of hospital medical staff in London and non- London regions per 100 000 population, together with percentage change in absolute numbers ofstaffbetween 1977 and 1988 1977
Acne Drug Depression Warnings Highlight Need for Expert Care
Authors: Lynne Lamberg
Journal: JAMA (1998)

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
Hepatitis C virus genotype 1b, cirrhosis, and risk of hepatocellular carcinoma
Authors: Angelo Sangiovanni, Massimo Iavarone
Journal: Hepatology (2007)

The extended follow-up of the original cohort of 163 patients with compensated cirrhosis due to hepatitis C virus (HCV) allowed Bruno and Colleagues1 to further support their opinion that genotype 1b of HCV is an independent strong predictor of hepatocellular carcinoma (HCC) in patients with cirrhosis. As acknowledged by the Authors, the rather controversial issue of HCV genotype being a predictor of HCC risk was not confirmed by several previous studies carried out in Italy, including our cohort study in Milan that started in 1986 and was lately re-analyzed in 2006.2 In terms of sample size, duration of surveillance, and number of events, our study was at least as informative as the study carried out by Bruno and Colleagues. We reported, in fact, 68 patients who developed a HCC during an average period of surveillance of 114 months (range: 1-199), with an annual incidence rate of 3.9%. In multivariate analysis, HCV genotype was not associated with an increased risk of HCC, clinical decompensation, or death. Similar conclusions about HCV genotype and HCC risk were also drawn by the experts participating at the National Institutes of Health (NIH) conference on HCC that was held in Bethesda, MD, in 2004.3 By definition, results of cohort studies might be affected by selection bias, which might have accounted for different findings, and in our opinion, this cannot be ruled out even in Bruno et al.'s article. However, independently of whether or not genotype 1b impacts on the natural history of hepatitis C cirrhosis, we disagree with the Authors' recommendations for more intensive surveillance in patients with cirrhosis infected with genotype 1b of HCV. According to widely accepted guidelines for surveillance with ultrasound of patients with cirrhosis,4, 5 surveillance intervals should not be customized according to the patient's level of HCC risk because HCC risk does not predict the speed of tumor growth, which is an important determinant of prognosis. Conversely, tumor growth dictates the intervals of surveillance because surveillance is aimed at identifying the smallest possible HCC nodes to improve treatment outcome. Because the median time of volume doubling of HCC nodes is 6 months, this time interval has been chosen as a reference standard for surveillance intervals. Angelo Sangiovanni M.D.*, Massimo Iavarone M.D.*, * 1st Division of Gastroenterology, AM & A Migliavacca Center for Liver Disease, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy.
Diffusion barriers in skin—a new method of comparison
Authors: M.I. FOREMAN, I. CLANACHAN, I.P. KELLY
Journal: British Journal of Dermatology (1983)

Journal Article Diffusion barriers in skin—a new method of comparison Get access M.I. FOREMAN, M.I. FOREMAN Department of Biochemistry, Organon Laboratories Limited, Newhouse mli 5sh, Scotland Search for other works by this author on: Oxford Academic Google Scholar I. CLANACHAN, I. CLANACHAN Department of Biochemistry, Organon Laboratories Limited, Newhouse mli 5sh, Scotland Search for other works by this author on: Oxford Academic Google Scholar I.P. KELLY I.P. KELLY Department of Biochemistry, Organon Laboratories Limited, Newhouse mli 5sh, Scotland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 108, Issue 5, 1 May 1983, Pages 549–553, https://doi.org/10.1111/j.1365-2133.1983.tb01055.x Published: 01 May 1983 Article history Accepted: 27 September 1982 Published: 01 May 1983
Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor
Authors: JE Gootenberg, FW Ruscetti, JW Mier, A Gazdar, RC Gallo
Journal: The Journal of Experimental Medicine (1981)

Three cell lines of mature T cell origin derived from patients with cutaneous T cell lymphoma-leukemias (CTCL) were found to be constitutive producers of T cell growth factor (L-TCGF). These are the first reported human cell lines which constitutively produce TCGF. Biologically active TCGF could also be eluted from the surface of these cells using an acid glycine buffer under conditions that maintained cell viability, and subcellular fractionation showed that almost all the TCGF activity was associated with the plasma membrane. Over 30 other human hematopoietic cell lines derived from other disorders were unable to produce TCGF even after induction, and their acid eluates did not contain TCGF activity. L-TCGF from CTCL lines had the same biological activity as TCGF obtained from normal leukocytes (N-TCGF) in that they both supported the long-term growth of normal T cells only after the cells were previously activated by antigen or lectin. Both L-TCGF and N-TCGF increased the rate of proliferation of TCGF-independent and TCGF-dependent CTCL cell lines. The same three factor-independent cell lines that released TCGF adsorbed TCGF in a cell-concentration, time-, and temperature-dependent manner. Since the CTCL cell lines produce TCGF, adsorb TCGF, and increase their proliferative rate in response to TCGF or a related molecule, it is suggested that this endogenously produced factor plays a role in maintaining the abnormal proliferation of these cells in culture as permanently growing cell lines independent of exogenous TCGF. However, this does not mean that this is an essential aspect of neoplastic transformation. Since it is unusual to develop these cell lines in the absence of the continuous need for added TCGF, "autostimulation" may be one of the many unusual variant phenotypic properties sometimes associated with neoplastic cells that gives them a selective advantage for in vitro growth.
The GMC, as usual, wastes our money
Authors: O. R. Dearlove
Journal: BMJ (2013)

The case of Patel v General Medical Council, in which the High Court overturned the GMC’s suspension of a GP for his alleged actions as a school governor,1 has not yet been reported. In the recent case of Rashid v GMC,2 the judge revoked the interim order because: “Such a sanction is neither necessary, desirable, or proportionate in this …
Prospective phase II trial to evaluate the complications and kinetics of chimerism induction following allogeneic hematopoietic stem cell transplantation with fludarabine and busulfan
Authors: Akiko M. Saito, Masahiro Kami, Shin‐Ichiro Mori, Yoshinobu Kanda, Ritsuro Suzuki, Shin Mineishi, Akiyoshi Takami, Shuichi Taniguchi, Yoshinobu Takemoto, Masamichi Hara, Masaki Yamaguchi, Masayuki Hino, Takashi Yoshida, Sung‐Won Kim, Akiko Hori, Yasuo Ohashi, Yoichi Takaue
Journal: American Journal of Hematology (2007)

Abstract This prospective trial assessed the safety and efficacy of allogeneic hematopoietic stem cell transplantation from a HLA‐matched donor with a reduced‐intensity regimen (RIST) consisting of iv fludarabine 30 mg/m 2 for 6 days and oral busulfan 4 mg/kg/day for 2 days in patients older than 50 years with hematological malignancies. Cyclosporine alone or cyclosporine with short‐term methotrexate was randomized for graft‐versus‐host disease prophylaxis. After 30 patients had been enrolled, an interim analysis was performed, and this report focuses on a precise evaluation of the toxicity profile and chimerism kinetics. Sustained engraftment in all patients, no severe regimen‐related toxicity (RRT) within 20 days, and no transplant‐related mortality through Day 100 were observed. T‐cell (CD3+) full‐donor (over 90%) chimerism was observed in 22 of the 30 patients, while the remaining eight had mixed‐donor chimerism over 77% on Day 90. Thereafter, five subsequently converted to full‐donor chimerism without donor lymphocyte infusion by day 120 ( n = 4) or Day 180 ( n = 1). Two showed persistent mixed chimerism without relapse through Day 180. Grade III–IV acute graft‐versus‐host disease and extensive chronic graft‐versus‐host disease occurred in 10% and 73%, respectively. With a median follow‐up of 1.5 years, overall survival and disease‐free survival at 1 year was 83% and 62%, respectively. Seven patients hematologically relapsed overall, and five of them had myelodysplastic syndrome with poor prognostic factors. In older patients, RIST with fludarabine and busulfan was associated with acceptable toxicities and a satisfactory antileukemia effect, regardless of the early chimerism status. Am. J. Hematol. 82:873–880, 2007. © 2007 Wiley‐Liss, Inc.
Circular RNA and miR-7 in Cancer
Authors: Thomas B. Hansen, Jørgen Kjems, Christian K. Damgaard
Journal: Cancer Research (2013)

MicroRNAs (miRNA) play important roles in fine-tuning gene expression and are often deregulated in cancer. The identification of competing endogenous RNA and circular RNA (circRNA) as important regulators of miRNA activity underscores the increasing complexity of ncRNA-mediated regulatory networks. Particularly, the recently identified circular RNA, ciRS-7, which acts as a designated miR-7 inhibitor/sponge, has conceptually changed the mechanistic understanding of miRNA networks. As miR-7 modulates the expression of several oncogenes, disclosing the regulation of miR-7 activity will likely advance the understanding of various cancer etiologies. Here, we review the current knowledge about the ciRS-7/miR-7 axis in cancer-related pathways and discuss possible models explaining the relevance of coexpressing miR-7 along with a circRNA inhibitor.
A mature second-person neuroscience needs a first-person (plural) developmental foundation
Authors: Charlie Lewis, James Stack
Journal: Behavioral and Brain Sciences (2013)

Schilbach et al.'s model assumes that the ability to "experience" minds is already present in human infants and therefore falls foul of the very intellectualist problems it attempts to avoid. We propose an alternative relational, action-based account, which attempts to grasp how the individual's construction of knowledge develops within interactions.
P612Involvement of the cardiomyokine FGF21 in protection against oxidative stress damage in the heart
Authors: A Planavila, I Redondo-Angulo, F Ribas, M Giralt, F Villarroya
Journal: Cardiovascular Research (2014)

Introduction: Oxidative stress mediated by reactive oxygen species (ROS) plays a striking role in the pathogenesis of heart failure and it has been shown that antioxidants attenuate cardiac remodeling in experimental models of cardiac damage. We have recently shown that FGF21, an endocrine member of the FGF family, is produced by the heart and exerts protective effects preventing cardiac hypertrophy development. The aim of the study was to determine the effects of FGF21 on oxidative stress processes in the heart. Methods: Studies in vivo were performed in hearts from wild-type (wt) and Fgf21-null mice. To assess the effects of the inflammatory process, mice were subjected to intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) for 4 hr. To induce cardiac hypertrophy mice were subjected to isoproterenol (ISO) infusion for 7 days. Cell culture of neonatal cardiomyocytes from rats and mice were used for the in vitro studies. Cardiomyocytes in culture were treated with LPS for 24 hr in the presence or absence of FGF21. Results: We found that treatment of FGF21 in cardiomyocytes in culture induces the expression of genes involved in anti-oxidative pathways such as mitochondrial uncoupling proteins (UCP2 and UCP3) and superoxide dismutase-2 (SOD2). Moreover, FGF21 reduces reactive oxygen species production in cardiac cells. In keeping with this, Fgf21-null mice presented reduced expression of anti-oxidant genes in response to stimulation with LPS-induced pro-inflammatory pathways or ISO-induced cardiac hypertrophy in the heart. Moreover, we showed that FGF21 is expressed in and released by cardiomyocytes in response to LPS, and its expression is under the control of the Sirt1 (sirtuin-1) pathway. Using neonatal cardiomyocytes in culture from wt and Fgf21-null mice we found that the FGF21 released by cardiomyocytes acts in an autocrine manner to protect the cells against oxidative stress. Finally, the analysis of samples from infarcted human hearts confirmed the association between FGF21 induction and the control of cardiac oxidative stress pathways (i.e. SOD2 induction). Conclusions: Our data indicate that FGF21 regulates in an autocrine manner genes involved in antioxidant pathways such as UCP2, UCP3 and SOD2 thus preventing reactive oxygen species production in cardiac cells. Therefore FGF21 acts in the heart as an antioxidant factor preventing pro-oxidative pathways induced by inflammatory/hypertrophic conditions.
Museum Scholars to Apply Holocaust Experience to 1990s Biomedical Issues
Authors: Andrew A. Skolnick
Journal: JAMA (1992)

IN APRIL 1993, a major new museum will open near the National Mall in Washington, DC, just 400 yards from the Washington Monument. The museum will not be another grandiose display of nature's wonders or of human achievements. It will be instead a place for remembering and for studying one of humankind's darkest deeds. In 1980, a unanimous act of Congress established the United States Holocaust Memorial Council and mandated the creation of a living memorial to the millions of victims of Nazi genocide. In keeping with the project's motto—"For the dead and the living, we must bear witness"— the council chose to build a museum and study center "to illuminate the future from the darkness of the past." <h3>Physicians' Holocaust Behavior</h3> A significant area of study at the museum will be the behavior of physicians in Central Europe during the Holocaust and how this knowledge can be used to
Role of thyroid hormone in regulation of isomyosin composition, contractility, and size of heterotopically isotransplanted rat heart.
Authors: B Korecky, R Zak, K Schwartz, V Aschenbrenner
Journal: Circulation Research (1987)

The role of thyroid hormone on the heart in terms of contractility, induction of growth, and selective synthesis of cardiac isomyosins was studied. After transplanting rat hearts from inbred hypothyroid donors into the abdomen of hypothyroid recipients of the same strain, two hearts were obtained in the same animal, both having reduced heart rate (200-250 bpm), decreased maximum rate of force, and high predominance of V3 isomyosin. The heart in situ carried a full load, while the transplant was denervated, beat isovolumically with minimum external work. After surgery, the recipient rats were put either on normal diet only (controls) or injected with a daily dose of T3 (average 200 micrograms/kg), which increased the heart rate to 340 bpm in 3 days (euthyroid level) and to 450 bpm in 7 days (hyperthyroid level). In T3-treated rats, the contractility of both hearts normalized in 7 days and showed hyperthyroid pattern in 14 days, while the mass of the in situ hearts increased to normal values in 7 days (+130 mg) and hypertrophied in 14 days (+340 mg), in contrast to the transplanted heart, which underwent atrophy (-90 mg and -210 mg) similar to that of control group (-225 mg). The predominant V3 isomyosin was completely reversed to V1 in two weeks in both hearts. Thus, T3 can neither stimulate cardiac growth nor can it attenuate the rate of atrophy in the denervated "nonworking" heart in spite of its direct effect on contractility and synthesis of isomyosins, which was similar to that observed in the in situ heart.
Propranolol Hydrochloride in the Treatment of Angina Pectoris
Authors: William M. Ginn
Journal: JAMA (1966)

PROPRANOLOL hydrochloride (Inderal), a new beta adrenergic receptor blocking agent, apparently possessing a potency ten to 20 times that of its predecessor, pronetalol,<sup>1</sup>yet lacking its tumor producing qualities in mice,<sup>2</sup>recently has received clinical trial in the treatment of angina pectoris. Strivastava and associates<sup>3</sup>using propranolol, 20 mg three times daily in a double-blind study of 20 patients exhibiting angina pectoris, found no statistically significant difference in frequency of angina pectoris or nitroglycerin consumption. However, Keelan<sup>4</sup>in a similar study of 19 patients but employing larger doses of propranolol, 30 mg three times daily, observed significant reduction in frequency of angina pectoris and in number of nitroglycerin tablets used. Gillam and Prichard,<sup>5</sup>utilizing maximum tolerated doses of propranolol, 30 mg to a ceiling of 100 mg four times daily, recorded significant improvement in all 14 patients studied. The present paper reports the results of
Retrospective Determination of the Area at Risk for Reperfused Acute Myocardial Infarction With T2-Weighted Cardiac Magnetic Resonance Imaging
Authors: Anthony H. Aletras, Gauri S. Tilak, Alex Natanzon, Li-Yueh Hsu, Felix M. Gonzalez, Robert F. Hoyt, Andrew E. Arai
Journal: Circulation (2006)

Background— The aim of this study was to determine whether edema imaging by T2-weighted cardiac magnetic resonance (CMR) imaging could retrospectively delineate the area at risk in reperfused myocardial infarction. We hypothesized that the size of the area at risk during a transient occlusion would be similar to the T2-weighted hyperintense region observed 2 days later, that the T2-weighted hyperintense myocardium would show partial functional recovery after 2 months, and that the T2 abnormality would resolve over 2 months. Methods and Results— Seventeen dogs underwent a 90-minute coronary artery occlusion, followed by reperfusion. The area at risk, as measured with microspheres (9 animals), was comparable to the size of the hyperintense zone on T2-weighted images 2 days later (43.4±3.3% versus 43.0±3.4% of the left ventricle; P =NS), and the 2 measures correlated ( R =0.84). The infarcted zone was significantly smaller (23.1±3.7; both P &lt;0.001). To test whether the hyperintense myocardium would exhibit partial functional recovery over time, 8 animals were imaged on day 2 and 2 months later. Systolic strain was mapped with displacement encoding with stimulated echoes. Edema, as detected by a hyperintense zone on T2-weighted images, resolved, and regional radial systolic strain partially improved from 4.9±0.7 to 13.1±1.5 ( P =0.001) over 2 months. Conclusions— These findings are consistent with the premise that the T2 abnormality depicts the area at risk, a zone of reversibly and irreversibly injured myocardium associated with reperfused subendocardial infarctions. The persistence of postischemic edema allows T2-weighted CMR to delineate the area at risk 2 days after reperfused myocardial infarction.