tbuckley/cabot-search huggingface dataset:
Tyrosine-kinase inhibition results in EGFR clustering at focal adhesions and consequent exocytosis in uPAR down-regulated cells of Head and Neck cancers
Authors: Samah Abu-Ali, Abbas Fotovati, Kanemitsu Shirasuna
Journal: Molecular Cancer (2008)

Antisense (AS) induced down-regulation of uPAR in ACCS adenoid-cyctic carcinoma cells decreased the cellular adhesion and invasion on various extracellular matrices. Additionally, ACCS-AS cells showed an increased EGFR expression and other behavioral similarities to NA-SCC, a typical highly proliferative but less invasive squamous cell carcinoma (SCC) cell line of the head and neck. ACCS, ACCS-AS and NA-SCC cells were used to elucidate the relationships between uPAR down-regulation and EGFR inhibition. Tyrosine kinase inhibitor Gefitinib (IRESSA, ZD 1839) significantly reduced the chemotactic cell migration and adhesion. This was associated with reduced EGFR and ERK activation. In addition, anti-proliferative effect of gefitinib in uPAR down-regulated ACCS-AS was significantly higher than parental ACCS, to levels comparable to gefitinib-sensitive NA-SCC cells. This was evidenced by both reduced dosage and duration of treatment. Furthermore, time-lapse videography showed that treatment with gefitinib was also associated with cell rounding and loss of pseudopodia, mostly in ACCS-AS rather than parental ACCS cells. There were also evidences of formation and exocytosis of vacuole-like structures in ACCS-AS, as well as NA-SCC, but not in parental ACCS cells. Interestingly, immunocytochemistry showed that the exocytotic vacuoles actually contained de-activated EGFR. Our results suggested that down-regulation of uPAR affected the fate of EGFR in high EGFR expressing cells. Furthermore, combining the uPAR down-regulation with EGFR inhibition showed a synergistic anti-tumor effect and might provide an alternative method to increase anti-proliferative effect of tyrosine kinase inhibitors with lower doses and duration to reduce their side effects during cancer control.
Cytotoxic effects of vascular smooth muscle cells of the chimeric toxin, heparin binding TGF -Pseudomonas exotoxin
Authors: Y.-M. Fu, E. A Mesri, Z.-X. Yu, R. J Kreitman, I. Pastan, S. E Epstein
Journal: Cardiovascular Research (1993)

Journal Article Cytotoxic effects of vascular smooth muscle cells of the chimeric toxin, heparin binding TGFα-Pseudomonas exotoxin Get access Ya-Min Fu, Ya-Min Fu National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA – Cardiology Branch: Y-M Fu, Z-X Yu, S E Epstein; Laboratory of Molecular Biology, Division of Cancer Diagnosis: E A Mesri, R J Kreitman, I Pastan. Correspondence to Dr Epstein (Building 10, Room 7B15). Search for other works by this author on: Oxford Academic PubMed Google Scholar Enrique A Mesri, Enrique A Mesri National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA – Cardiology Branch: Y-M Fu, Z-X Yu, S E Epstein; Laboratory of Molecular Biology, Division of Cancer Diagnosis: E A Mesri, R J Kreitman, I Pastan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Zu-Xi Yu, Zu-Xi Yu National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA – Cardiology Branch: Y-M Fu, Z-X Yu, S E Epstein; Laboratory of Molecular Biology, Division of Cancer Diagnosis: E A Mesri, R J Kreitman, I Pastan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert J Kreitman, Robert J Kreitman National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA – Cardiology Branch: Y-M Fu, Z-X Yu, S E Epstein; Laboratory of Molecular Biology, Division of Cancer Diagnosis: E A Mesri, R J Kreitman, I Pastan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ira Pastan, Ira Pastan National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA – Cardiology Branch: Y-M Fu, Z-X Yu, S E Epstein; Laboratory of Molecular Biology, Division of Cancer Diagnosis: E A Mesri, R J Kreitman, I Pastan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Stephen E Epstein Stephen E Epstein National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA – Cardiology Branch: Y-M Fu, Z-X Yu, S E Epstein; Laboratory of Molecular Biology, Division of Cancer Diagnosis: E A Mesri, R J Kreitman, I Pastan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 9, September 1993, Pages 1691–1697, https://doi.org/10.1093/cvr/27.9.1691 Published: 01 September 1993 Article history Received: 24 March 1993 Accepted: 02 June 1993 Published: 01 September 1993
Oxidative stress and regulation of glutathione in lung inflammation
Authors: I. Rahman, W. MacNee
Journal: European Respiratory Journal (2000)

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance, a major cause of cell damage. The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox-sensitive transcription factors such as nuclear factor-KB, and activator protein-1 (AP-1), which regulate the genes for pro-inflammatory mediators and protective antioxidant genes. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro-inflammatory processes in the lungs. Recent findings have suggested that GSH is important in immune modulation, remodelling of the extracellular matrix, apoptosis and mitochondrial respiration. The rate-limiting enzyme in GSH synthesis is gamma-glutamylcysteine synthetase (gamma-GCS). The human gamma-GCS heavy and light subunits are regulated by AP-1 and antioxidant response elements and are modulated by oxidants, phenolic antioxidants, growth factors, and inflammatory and anti-inflammatory agents in lung cells. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis and asthma. The imbalance and/or genetic variation in antioxidant gamma-GCS and pro-inflammatory versus antioxidant genes in response to oxidative stress and inflammation in some individuals may render them more susceptible to lung inflammation. Knowledge of the mechanisms of GSH regulation and balance between the release and expression of pro- and anti-inflammatory mediators could lead to the development of novel therapies based on the pharmacological manipulation of the production as well as gene transfer of this important antioxidant in lung inflammation and injury. This review describes the redox control and involvement of nuclear factor-kappaB and activator protein-1 in the regulation of cellular glutathione and gamma-glutamylcysteine synthetase under conditions of oxidative stress and inflammation, the role of glutathione in oxidant-mediated susceptibility/tolerance, gamma-glutamylcysteine synthetase genetic susceptibility and the potential therapeutic role of glutathione and its precursors in protecting against lung oxidant stress, inflammation and injury.
Separation of sublethal and lethal effects of polymorphonuclear leukocytes on Escherichia coli.
Authors: B A Mannion, J Weiss, P Elsbach
Journal: Journal of Clinical Investigation (1990)

Escherichia coli ingested by PMN promptly stop growing and form no colonies in nutrient agar, but metabolize near normally for up to several hours. The bactericidal/permeability increasing protein (BPI) of PMN also inhibits E. coli growth without initial metabolic impairment. We recently showed that BPI-treated E. coli, although unable to grow in normal nutrient agar, can form colonies in this medium plus 0.1% BSA, as long as their metabolism is maintained, indicating that biochemical impairment is a better indicator of death than growth arrest (1990. J. Clin. Invest. 85:853-860). We have now reexamined the fate of ingested E. coli. Rabbit PMN ingest greater than 85% of several rough E. coli strains in 15 min, but greater than 80% of these bacteria, while unable to form colonies in conventional agar, grow normally on agar plus 0.1% BSA. Thus, the PMN under these conditions promptly stop growth of ingested E. coli without killing. Adding nonlethal concentrations of normal human serum (NHS) before, but not after ingestion, accelerates killing and, in parallel, loss of bacterial metabolism (t1/2 less than 0.5 h vs. greater than 3 h, respectively, with and without NHS). The rapid killing of both rough and smooth E. coli pretreated with NHS is lost after C7 depletion (C7-D) and restored when C7 is replenished. Similar results are obtained with human PMN. In contrast, ingested Staphylococcus epidermidis, opsonized with either NHS or C7-D serum rapidly stop metabolizing and do not form colonies in nutrient agar with or without BSA. Respiratory burst activity is the same during ingestion of E. coli (with or without NHS) and S. epidermidis. Killing of E. coli J5 (however, not of O111-B4) by BPI is also accelerated by pretreatment with NHS but not C7-D human serum. These findings indicate that late complement components are needed for efficient killing of both rough and smooth E. coli by PMN, and that BPI is the principal intracellular agent acting on ingested rough E. coli.
Lung transplant and cystic fibrosis: what's new from the UK and France?
Authors: P. G Noone
Journal: Thorax (2008)

Although the median survival for patients with cystic fibrosis (CF) has improved steadily over the past several decades, many patients go on to develop respiratory failure from progressive lung disease, eventually requiring lung transplantation for extended survival.1 Although many years have elapsed since the first lung transplants were performed for CF, the field is not without controversy.2 The paper recently published by Liou et al is one recent example, suggesting that lung transplant for most children with CF under 18 years of age offers no survival advantage.2 The complex statistical methodology and conclusions have since been challenged and rebutted by several lung transplant experts.3–5 Controversial issues like this often reflect the shortage of randomised controlled trials for many aspects of lung transplant. Although there is much published material related to lung transplant, many protocols are based on retrospective data, or are rather centre or region specific. Although impure because of multiple confounding factors, such as small sample sizes, and varying surgical and medical protocols, these data do provide a reasonable template to formulate and update lung transplant protocols.

Two such datasets6 7 are published in this issue of Thorax (see pages 725 and 732) . The first represents the experience of a single centre in the UK, accounting for a large proportion of lung transplants for CF in Britain,6 while the second paper from France addresses a difficult issue—that is, the risks of performing lung transplantation in patients infected with Burkholderia cepacia complex (BCC) organisms.7 The papers are complementary: the UK experience is a general report, excluding a detailed analysis of outcomes in patients with BCC (these data are promised shortly), while the French paper is BCC specific.

The Newcastle Lung Transplant Centre can take pride in its achievements as …
Cardioprotection of Ischemia/Reperfusion Injury by Cholesterol-Dependent MG53-Mediated Membrane Repair
Authors: Xianhua Wang, Wenjun Xie, Yi Zhang, Peihui Lin, Liang Han, Peidong Han, Yanru Wang, Zheng Chen, Guangju Ji, Ming Zheng, Noah Weisleder, Rui-Ping Xiao, Hiroshi Takeshima, Jianjie Ma, Heping Cheng
Journal: Circulation Research (2010)

Unrepaired cardiomyocyte membrane injury causes irreplaceable cell loss, leading to myocardial fibrosis and eventually heart failure. However, the cellular and molecular mechanisms of cardiac membrane repair are largely unknown. MG53, a newly identified striated muscle-specific protein, is involved in skeletal muscle membrane repair. But the role of MG53 in the heart has not been determined.We sought to investigate whether MG53 mediates membrane repair in cardiomyocytes and, if so, the cellular and molecular mechanism underlying MG53-mediated membrane repair in cardiomyocytes. Moreover, we determined possible cardioprotective effect of MG53-mediated membrane repair.We demonstrated that MG53 is crucial to the emergency membrane repair response in cardiomyocytes and protects the heart from stress-induced loss of cardiomyocytes. Disruption of the sarcolemmal membrane by mechanical, electric, chemical, or metabolic insults caused rapid and robust translocation of MG53 toward the injury sites. Ablation of MG53 prevented sarcolemmal resealing after infrared laser-induced membrane damage in intact heart, and exacerbated mitochondrial dysfunction and loss of cardiomyocytes during ischemia/reperfusion injury. Unexpectedly, the MG53-mediated cardiac membrane repair was mediated by a cholesterol-dependent mechanism: depletion of membrane cholesterol abolished, and its recovery restored injury-induced membrane translocation of MG53. The redox status of MG53 did not affect initiation of MG53 translocation, whereas MG53 oxidation conferred stability to the membrane repair patch.Thus, cholesterol-dependent MG53-mediated membrane repair is a vital, heretofore unappreciated cardioprotective mechanism against a multitude of insults and may bear important therapeutic implications.
MOLECULAR BIOLOGY OF DIABETES INSIPIDUS
Authors: T. Mary Fujiwara, M.Sc, Kenneth Morgan, Ph.D, Daniel G. Bichet, M.D
Journal: Annual Review of Medicine (1995)

▪ Abstract The identification, characterization, and mutational analysis of three different genes, namely the prepro-arginine-vasopressin-neurophysin II gene (prepro-AVP-NPII), the arginine-vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin-2, AQP2), provide the basis for our understanding of three different hereditary forms of diabetes insipidus: autosomal dominant neurogenic diabetes insipidus, X-linked nephrogenic diabetes insipidus, and autosomal recessive nephrogenic diabetes insipidus, respectively. These advances provide diagnostic tools for physicians caring for these patients.
Volume-Pressure Curves of the Human Arm
Authors: A. LANARI, B. BROMBERGER-BARNEA, A. LAMBERTINI
Journal: Circulation Research (1957)

After interruption of the circulation, pressure changes in the brachial artery and a forearm vein were recorded and plotted against volume of blood injected intra-arterially expressed in ml./100 cc. of arm tissue. The resulting volume-pressure curves showed a steep rise with the first injection, a linear rise in the center section and a rapid increase during the last injection. These curves were not influenced by either sex, age or moderate systemic hypertension.
Basophils Play a Critical Role in the Development of IgE-Mediated Chronic Allergic Inflammation Independently of T Cells and Mast Cells
Authors: Kaori Mukai, Kunie Matsuoka, Choji Taya, Hidenori Suzuki, Hiroo Yokozeki, Kiyoshi Nishioka, Katsuiku Hirokawa, Maki Etori, Makoto Yamashita, Toshiyuki Kubota, Yoshiyuki Minegishi, Hiromichi Yonekawa, Hajime Karasuyama
Journal: Immunity (2005)
Cancer Chemopreventive Potential of Sulforamate, a Novel Analogue of Sulforaphane That Induces Phase 2 Drug-metabolizing Enzymes
Authors: Clarissa Gerhäuser, Min You, Jinfang Liu, Robert M. Moriarty, Michael Hawthorne, Rajendra G. Mehta, Richard C. Moon, John M. Pezzuto
Journal: Cancer Research (1997)

Chemoprevention involves the use of natural or synthetic substances to reduce the risk of developing cancer. Two dietary components capable of mediating chemopreventive activity in animal models by modulation of drug-metabolizing enzymes are sulforaphane, an aliphatic isothiocyanate, and brassinin, an indole-based dithiocarbamate, both found in cruciferous vegetables. We currently report the synthesis and activity of a novel cancer chemopreventive agent, (+/-)-4-methylsulfinyl-1-(S-methyldithiocarbamyl)-butane (trivial name, sulforamate), an aliphatic analogue of brassinin with structural similarities to sulforaphane. This compound was shown to be a monofunctional inducer of NAD(P)H:quinone oxidoreductase [quinone reductase (QR)], a Phase II enzyme, in murine Hepa 1c1c7 cell culture and two mutants thereof. Induction potential was comparable to that observed with sulforaphane (concentration required to double the specific activity of QR, approximately 0.2 microM), but cytotoxicity was reduced by about 3-fold (IC50 approximately 30 microm). In addition, sulforaphane, as well as the analogue, increased glutathione levels about 2-fold in cultured Hepa 1c1c7 cells. Induction of QR was regulated at the transcriptional level. Using Northern blotting techniques, time- and dose-dependent induction of QR mRNA levels were demonstrated in Hepa 1c1c7 cell culture. To further investigate the mechanism of induction, HepG2 human hepatoma cells were transiently transfected with QR-chloramphenicol acetyltransferase plasmid constructs containing various portions of the 5'-region of the QR gene. Sulforaphane and the analogue significantly induced (P < 0.0001) CAT activity at a concentration of 12.5 microM by interaction with the antioxidant responsive element (5-14-fold induction) without interacting with the xenobiotic responsive element. Moreover, both compounds significantly induced mouse mammary QR and glutathione S-transferase activity (feeding of 3 mg/mouse intragastric for 4 days), whereas the elevation of hepatic enzyme activities was less pronounced. Both sulforaphane and the analogue were identified as potent inhibitors of preneoplastic lesion formation in carcinogen-treated mouse mammary glands in organ culture (84 and 78% inhibition at 1 microm, respectively). On the basis of these results, the sulforaphane analogue can be regarded as a readily available promising new cancer chemopreventive agent.
The Swiss Health System
Authors: Uwe E Reinhardt
Journal: JAMA (2004)

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
T helper cell 2 immune skewing in pregnancy/early life: chemical exposure and the development of atopic disease and allergy
Authors: J.P. McFadden, J.P. Thyssen, D.A. Basketter, P. Puangpet, I. Kimber
Journal: British Journal of Dermatology (2014)

During the last 50 years there has been a significant increase in Western societies of atopic disease and associated allergy. The balance between functional subpopulations of T helper cells (Th) determines the quality of the immune response provoked by antigen. One such subpopulation – Th2 cells – is associated with the production of IgE antibody and atopic allergy, whereas, Th1 cells antagonize IgE responses and the development of allergic disease. In seeking to provide a mechanistic basis for this increased prevalence of allergic disease, one proposal has been the ‘hygiene hypothesis’, which argues that in Westernized societies reduced exposure during early childhood to pathogenic microorganisms favours the development of atopic allergy. Pregnancy is normally associated with Th2 skewing, which persists for some months in the neonate before Th1/Th2 realignment occurs. In this review, we consider the immunophysiology of Th2 immune skewing during pregnancy. In particular, we explore the possibility that altered and increased patterns of exposure to certain chemicals have served to accentuate this normal Th2 skewing and therefore further promote the persistence of a Th2 bias in neonates. Furthermore, we propose that the more marked Th2 skewing observed in first pregnancy may, at least in part, explain the higher prevalence of atopic disease and allergy in the first born.
Endoscopic Enzymatic Dissolution
Authors: R. Carter Davis
Journal: JAMA (1974)

FIBEROPTIC gastroscopies are largely responsible for the sharp increase in the diagnosis of postoperative gastric phytobezoars. The latter have been noted as a postoperative complication in 14% of all gastrectomies in one series.<sup>1</sup>In our recent experience with five documented cases in 1973, we have had surprisingly good results with nonsurgical management. Our five patients, two men and three women, ranged in age from 42 to 57 years. Four of the five were edentulous. They gave a history of ingesting citrus fruits, apple cores, and apple peels. All had undergone partial gastrectomy and vagotomy (Billroth II) from six weeks to 11 years before admission. All were admitted for episodes of epigastric discomfort with associated nausea and vomiting. Upper-gastrointestinal roentgenographic series were done on the patients before admission (Fig 1), and gastric bezoar was originally suspected in only one of them. In the other four, the roentgenograms were thought to
Perforation of the Uterus With the Lippes Loop
Authors: F. Douglas Scutch field
Journal: JAMA (1969)

Eight uterine perforations with the Lippes loop were seen by the members of the Emory University Family Planning Program at Grady Memorial hospital. This program has been responsible for 6,839 insertions of the Lippes loop. We feel that uterine perforation frequently involves one physician. The use of a uterine sound prior to insertion can help prevent uterine perforations. The most common complaints are pregnancy without a known expulsion and inability to see the strings of the intrauterine contraceptive device during pelvic examination or both.
From inhibition of radiographic progression to maintaining structural integrity: a methodological framework for radiographic progression in rheumatoid arthritis and psoriatic arthritis clinical trials
Authors: Robert Landewé, Vibeke Strand, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

Usually, a clinical trial in rheumatoid arthritis and psoriatic arthritis aiming to demonstrate that a new antirheumatic drug treatment can inhibit progression of structural damage has a 'superiority design': The new treatment is compared to placebo or to another active treatment. Currently, many new drug treatments have shown to be able to completely suppress progression (progression rates close to zero). For largely unknown reasons, during the last 10 years, radiographic progression rates in clinical trials have gradually decreased, so that progression rates in the comparator groups are often too low to demonstrate meaningful inhibition, and thus superiority of the new treatment. We here propose an alternative framework to demonstrate that new treatments have the ability to 'preserve structural integrity' rather than to 'inhibit radiographic progression'. Anno 2013, preserving structural integrity is conceptually more realistic than inhibiting radiographic progression.