tbuckley/cabot-search huggingface dataset:
Abstract 4293: In vivo imaging and tracking of a PARP inhibitor at single-cell resolution
Authors: Katherine Yang, Greg Thurber, Thomas Reiner, Rainer Kohler, Ralph Weissleder
Journal: Cancer Research (2012)

Abstract PARP is an enzyme involved in sensing single-stranded DNA breaks and plays a critical role in the organization of DNA damage repair. Several PARP inhibitors have been developed for clinical use, particularly in breast and ovarian cancers with BRCA mutations. Despite the scientific rationale and promising early clinical results with PARP inhibitors, more advanced clinical trials in breast cancer have been disappointing. One of the questions arising from these trials is to better understand why the PARP inhibitors failed. We used a window-chamber system in mice to image the distribution and function of model PARP inhibitors such as AZD2281-Bodipy. Specifically, we measured the kinetics of vascular, cellular, and subcellular uptake and distribution of AZD2281-Bodipy in breast (MDA-MB-231, MDA-MB-436) and ovarian (OVCAR429, A2780) tumors over time. Additionally, using the fluorescently-labeled inhibitor, we were able to examine the heterogeneity of AZD2281 localization in single cancer cells in vivo. Our data provide the first example of single-cell distribution of fluorescent small molecule inhibitors. When coupled with reporter cell lines (e.g. for apoptosis, DNA damage, autophagy, and senescence), this approach will be a powerful tool to understand drug action in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4293. doi:1538-7445.AM2012-4293
Steroids: Keys to Life
Authors: Howard S. Pitkow
Journal: JAMA (1982)

Witzmann successfully presents steroids in an organized fashion as evidenced by the natural progression of topics: discovery of the biologic steroids, the steroid mechanism, deliberate synthesis of steroids, and steroids of the future. A historical perspective of the advances in steroid research through the important work of many investigators, including several Nobel Prize laureates, is examined in detail. Some of these major discoveries include Wieland's first steroid formula, Butenandt's sex steroids, Ruzicka's synthesis of the first steroid, Hench's work on adrenal corticoids, and Sutherland's mechanism of hormone action. Starting with cholesterol and ergosterol, the reader is given insight into the research that led to the biosynthesis of many of the steroid hormones and their isolation. The spectrum of areas covered includes cholesterol and the cell membrane, vitamin D and the skeletal framework, bile acids and the digestion of fat, endocrine secretion and control, sex hormones and reproduction, protective steroids and
An uncommon presentation of a common cancer
Authors: R. Tadiparthi, K. Ponnuru, R. Cherian, S. Mathur, A. Rastogi
Journal: Endoscopy (2010)

A 67-year-old Caucasian man presenting with episodic right upper quadrant pain and weight loss of 9 kg (20 lb) was found to have elevated levels of alkaline phosphatase (180 IU/mL). An abdominal ultrasound revealed cholelithiasis with no biliary ductal dilatation. Endoscopic retrograde cholangiography (ERC) revealed a normal common bile duct (CBD) and right and left hepatic ducts ([Fig. 1]).
Exfoliative esophagitis and esophageal ulcer induced by dabigatran
Authors: M. Okada, K. Okada
Journal: Endoscopy (2012)

A 79-year-old Japanese man was diagnosed as having atrial fibrillation at a private hospital 5 days before coming to our clinic, where he was prescribed dabigatran at 110 mg twice daily. Approximately 10 minutes after taking dabigatran with about 50 ml of water – one-third of his usual amount – on the morning of the third day, the patient had odynophagia, retrosternal burning pain, and dysphagia. He reported to our clinic 2 days later.
NICKEL STEEL FOR SURGICAL INSTRUMENTS.
Authors: EDMUND ANDREWS
Journal: JAMA (1894)

Nickel steel has become famous the world over for its capacity to form an impenetrable ship armor. It is an alloy of steel with about 3.2 per cent. of nickel. Its color and appearance are those of ordinary steel, but its qualities are remarkable. Its tensile strength is raised by the addition of the nickel to about 200,000 pounds per square inch, which is nearly as great as that of the best hardened steel, without any of its brittleness. On the contrary, it has extraordinary toughness, and resists cannon shot to a degree far beyond any armor plating before known. The commander of the United States Arsenal in Springfield, Mass., informs me that he has tried to make rifle barrels of it, but he finds it almost impossible to turn it or bore it. It seemed likely that qualities like this might be of use in certain surgical instruments. Having
Multiple Breast Cancer Risk Factors Do Not Improve Patient Acceptance of Chemoprevention.
Authors: S. Lo, E. Henry, K. Rychlik, P. Mumby, L. Bowling, P. Robinson, K. Albain
Journal: Cancer Research (2009)

Abstract Background: Patients may be at increased risk of developing breast cancer due to hereditary or familial risk or a pathological diagnosis of breast atypia or lobular carcinoma in situ (LCIS). Although tamoxifen and raloxifene are effective and approved chemopreventive agents to reduce risk of developing breast cancer in high risk individuals, acceptance of chemoprevention as a risk reduction strategy is low. Our objective was to assess whether chemoprevention is more readily accepted by those at genetic or familial risk versus pathologic risk, and if the presence of multiple breast cancer risk factors improves chemoprevention acceptance.Methods: All patients seen at the Loyola University Cancer Risk Assessment and Prevention clinic completed information including demographics, health, family and social history. Patients with a family history of either a first or second degree family member with breast cancer (FH) were compared to those who presented due to atypia or LCIS on breast biopsy as well as those with an elevated Gail score. Acceptance of risk reducing strategies between these groups was compared.Results: The initial 115 patients presenting to the clinic were analyzed. Thirty-six (31%) women had FH only, 26 (23%) had a biopsy with atypia or LCIS only, 10 (9%) had an elevated Gail score, 17 (15%) had a biopsy indicating atypia or LCIS plus FH, and 26 (23%) had an elevated Gail plus FH. Seventy-three patients were candidates for chemoprevention; 16 (22%) accepted chemoprevention. Patients with a FH plus atypia/LCIS did not accept chemoprevention more than patients with FH alone (p=1.00). Patients with a FH plus atypia/LCIS did not accept chemoprevention more than than patients with atypia/LCIS alone (p=0.451). Pts with elevated Gail plus FH did not accept chemoprevention more than patients with elevated Gail alone (p=0.144). Four women in the FH group were known BRCA mutation carriers; all elected to proceed with risk reducing surgery, none accepted chemoprevention.Conclusions: Acceptance of chemoprevention is low in women at genetic or familial risk, those at risk due to atypia/LCIS, and those with an elevated Gail score. Having both familial and pathologic risk factors for breast cancer development did not increase acceptance of chemoprevention. Better understanding of women's comprehension of breast cancer risk, and barriers to patient acceptance of chemoprevention are needed. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1039.
Differential expression of complement C3 and C4 in the human kidney.
Authors: T R Welch, L S Beischel, D P Witte
Journal: Journal of Clinical Investigation (1993)

Complement activation is associated with a variety of immunologically-mediated renal diseases. Proximal tubular epithelial cells in situ constitutively express messenger RNA for C4 of the complement system. These same epithelial cells in culture have been reported to contain message for C3 and to secrete this protein when stimulated by IL-2. The present study compared the in situ localization of C3 and C4 message in parallel in a variety of renal biopsy and nephrectomy specimens. All adequate tissue samples (n = 23) had C4 mRNA throughout in the cortical tubular epithelium. Although C3 message was also expressed in tubular epithelial cells, there was much greater variation in its distribution. mRNA for C3 was not detected in histologically normal specimens (n = 4) either by in situ or Northern hybridization. Focal C3 message correlated with focal histologic abnormalities (e.g., focal glomerulosclerosis), while more generalized C3 signal occurred in specimens with more diffuse inflammatory processes (e.g., SLE). Infiltrating inflammatory cells and cells of the glomeruli were uniformly negative for C3 (and C4) message. Tubular C3 and C4 mRNA appeared to be translated, since selected specimens showed cytoplasmic staining by monoclonal antibodies to C3c and C4c. These observations are consistent with the hypothesis that local production of inflammatory mediators could induce C3 synthesis in the renal interstitium, with the possibility that subsequent complement activation could enhance the pathogenic process.
Effects of pollen and nasal glucocorticoid on FOXP3<sup>+</sup>, GATA‐3<sup>+</sup> and T‐bet<sup>+</sup> cells in allergic rhinitis
Authors: C. Malmhäll, A. Bossios, T. Pullerits, J. Lötvall
Journal: Allergy (2007)

Background: T‐regulatory cells (Treg) affect the balance of T H 2 and T H 1 cells. Treg, T H 2 and T H 1 cells are regulated by the FOXP3, GATA‐3 and T‐bet transcription factors respectively. Our aim was to determine the number of FOXP3 + , GATA‐3 + and T‐bet + cells in nasal mucosa in symptom‐free allergic rhinitis (AR) patients vs healthy controls, as well as the effects of natural pollen exposure and concomitant nasal glucocorticoid treatment on these cells. Methods: Nasal biopsies were taken from healthy controls and patients with grass‐pollen AR preseason. The AR patients were randomized to receive treatment with either fluticasone propionate (FP) or a placebo, and additional biopsies were taken during the pollen season. FOXP3 + , GATA‐3 + and T‐bet + cells in nasal mucosa were quantified by immunohistochemistry. Results: The number of FOXP3 + and GATA‐3 + cells, but not T‐bet + cells, was significantly higher in AR patients vs controls preseason. The number of FOXP3 + cells remained unchanged in the former group after the pollen season but decreased significantly in the nasal mucosa as a result of FP treatment. The pollen season substantially increased the number of GATA‐3 + cells, which was inhibited by FP. The number of T‐bet + cells was not affected by pollen or FP. Conclusion: These data suggest that nasal glucocorticoids attenuate the allergic inflammation partly by reducing the number of T H 2 cells, but not by means of local upregulation of Treg cells. The local relationship between T H 1 and T H 2 cells as well as between Treg and T H 2 is maintained by nasal glucocorticoid treatment.
Mast Cells in Rupture-Prone Areas of Human Coronary Atheromas Produce and Store TNF-α
Authors: Maija Kaartinen, Antti Penttila¨, Petri T. Kovanen
Journal: Circulation (1996)

Background Mast cells, a cell type involved in inflammatory reactions, are present in coronary atheromas and localize to the erosion or rupture site of atheromas in myocardial infarction. Here we report the presence of TNF-α, a proinflammatory cytokine, in mast cells of human coronary atheromas. Methods and Results From samples of 37 coronary arteries from subjects autopsied for medicolegal reasons, sections of the bifurcation area of the left coronary artery were stained immunohistochemically for mast cells and TNF-α. In addition, macrophages, T lymphocytes, smooth muscle cells, and endothelial cells were investigated for their content of TNF-α. In normal intimas and fatty streaks, none of the cell types studied were TNF-α–positive. In 14 of the 24 atheromas found, TNF-α–positive cells were present. Of the total number of mast cells, 23% stained for TNF-α; of the macrophages, 1.3%; and of the smooth muscle cells, 0.4%. The majority (55%) of TNF-α–positive mast cells in the atheromas were located in the shoulder region and the remaining 35% in the cap and 10% in the core regions. Immunoelectron microscopy showed that the TNF-α in mast cells resided within their cytoplasmic secretory granules, demonstrating that these cells contain stores of TNF-α that will be released on degranulation. Conclusions This study demonstrates the presence of mast cells with TNF-α–containing secretory granules, particularly in the shoulder region of human coronary atheromas. By releasing their TNF-α, mast cells may play an active role in the inflammatory reactions of these rupture-prone areas of atheromas.
A Blinded, Randomized Comparison of a Novel, Low-Dose, Triple Regimen with Fleet Phospho-Soda: A Study of Colon Cleanliness, Speed and Success of Colonoscopy
Authors: A. P. Chilton, M. O'Sullivan, M. A. Cox, D. E. Loft, C. U. Nwokolo
Journal: Endoscopy (2002)

Background and Study Aims: A clean colon is essential for an efficient examination. The aim of this study was to compare a novel low-dose, low volume triple regimen with Fleet Phospho-soda.
Tissue plasminogen activator promotes platelet disaggregation in plasma.
Authors: J Loscalzo, D E Vaughan
Journal: Journal of Clinical Investigation (1987)

We studied the disaggregation of human platelets by tissue-type plasminogen activator (t-PA). When added to a suspension of human platelets induced to aggregate in plasma with adenosine 5'-diphosphate, t-PA promoted disaggregation of platelets over several minutes. Addition of fresh plasma or purified human fibrinogen to disaggregated platelets facilitated (reversible) aggregation and subsequent disaggregation. Aspirin treatment of platelets markedly potentiated the ability of t-PA to induce disaggregation. Disaggregation was inhibited by alpha-2-antiplasmin. Comparative analysis of the rate of proteolysis of platelet-bound fibrinogen with that of ambient plasma fibrinogen suggested that fibrinogenolysis of cohesive fibrinogen occurred more rapidly than fibrinogenolysis of ambient fibrinogen. These data demonstrate that t-PA facilitates platelet disaggregation in plasma through kinetically selective proteolysis of cohesive fibrinogen by plasmin, and suggest that thrombolytic mechanisms may serve both to remove platelets from platelet-fibrin thrombi and to disperse circulating platelet aggregates.
Making the Rounds
Authors: George Young
Journal: Annals of Internal Medicine (2000)

Ad Libitum17 October 2000Making the RoundsGeorge Young, MDGeorge Young, MDBoulder, CO 80304 (Young)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-8-200010170-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail You know her … skinny, blond, pinched mouth, pinched brow, handshakelike a dead trout, paineverywhere, making the rounds, to neurologist,cardiologist, gastroenterologist, psychiatrist, rheumatologist, referredby her PCP (God bless him)to you.She is separated, getting a divorce, can't sleep. System Review lights uplike a pinball machine. Into the ER last week twicefor Demerol for headaches, chest pain.Scheduled foran MRI and a treadmill ECG next week. She asksabout Mayo's. You wonder … would it helpif you could just wrap your arms around her, smooththe damp tendrils of hair from her temple, kissher pale forehead?No! That is not allowed!You ... Author, Article, and Disclosure InformationAffiliations: Boulder, CO 80304 (Young)Corresponding Author: George Young, MD, Boulder Medical Center, 2750 Broadway, Boulder, CO 80304. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 October 2000Volume 133, Issue 8Page: 608KeywordsDeoxyadenosine monophosphateGastroenterology and hepatologyIschemiaMouthPainRheumatic painSleepSystematic reviews ePublished: 17 October 2000 Issue Published: 17 October 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
COMBINED SYSTEM DISEASE IN VITAMIN B_12-TREATED PERNICIOUS ANEMIA
Authors: KUNIO OKUDA
Journal: Annals of Internal Medicine (1966)

Letters and Comments1 October 1966COMBINED SYSTEM DISEASE IN VITAMIN B12-TREATED PERNICIOUS ANEMIAKUNIO OKUDA, M.D., HISATOSHI TAKEDATSU, M.D.KUNIO OKUDA, M.D.Search for more papers by this author, HISATOSHI TAKEDATSU, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-65-4-865_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: We read with great interest the article by Dr. G. J. Ellis and his associates in the March 1966 issue of this journal on a patient with pernicious anemia who developed clinical evidence of combined system disease during the course of adequate parenteral vitamin B12 therapy.Their patient apparently had recurrent bouts of diarrhea and then developed posterolateral spinal column involvement in spite of B12administration. The spinal lesion in this case might be entirely unrelated to B12deficiency and reminds us of a new disease entity that has recently received general attention in Japan. The disease...References1. KUSUI K: Symposium on non-specific encephalomyelitis. Jap. J. Med. 4: 177, 1965. CrossrefGoogle Scholar2. OKUDA K: Jap. Med. J. 2159: 8, 1965. Google Scholar3. SHINGU M: J. Jap. Soc. Infect. Dis. 39: 139, 1965. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine Kurume University School of Medicine Kurume, Japan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1966Volume 65, Issue 4Page: 865-865KeywordsDiarrheaLesionsPernicious anemiaSpineSystemic diseases Issue Published: 1 October 1966 PDF DownloadLoading ...
Solid Organ Transplantation. 2: Ethical Considerations
Authors: Paul Kefalides
Journal: Annals of Internal Medicine (1999)

Currents19 January 1999Solid Organ Transplantation. 2: Ethical ConsiderationsPaul Kefalides, MDPaul Kefalides, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-2-199901190-00101 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the United States, 61 000 individuals await organ transplants. Developing new approaches to deal with the waiting list for solid organs is an ongoing struggle, as explained in the 5 January issue of Annals. However, addressing the ethical dilemma of placing healthy individuals at risk for the benefit of another individual—particularly when the donor is not a blood relative or spouse—is perhaps a greater challenge.“Frequently the question we have is: ‘Is money being paid under the table?’,” F. John Gennari, MD, Professor of Medicine and Director of Nephrology at the University of Vermont, pointed out.Donors and Recipients... Author, Article, and Disclosure InformationAffiliations: Corresponding Author: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPerspective review on solid-organ transplant: needs in point-of-care optical biomarkersSocial, ethical and legal issues in chronic hemodialysis and transplantation 19 January 1999Volume 130, Issue 2Page: 169-170KeywordsBlood banksLegislationLiverMedical ethicsMedical servicesMotivationNephrologySolid organ transplantationSurgeryTransplantation Issue Published: 19 January 1999 CopyrightCopyright © 1999 by American College of Physicians. All Rights Reserved.Loading ...
Therapeutic Evaluation of Epstein-Barr Virus-encoded Latent Membrane Protein-1 Targeted DNAzyme for Treating of Nasopharyngeal Carcinomas
Authors: Ya Cao, Lifang Yang, Wuzhong Jiang, Xiaoyi Wang, Weihua Liao, Guolin Tan, Yuping Liao, Yuanzheng Qiu, Deyun Feng, Faqing Tang, Bob L Hou, Ling Zhang, Jia Fu, Fengjiao He, Xiaoyu Liu, Wenjuan Jiang, Tubao Yang, Lun-Quan Sun
Journal: Molecular Therapy (2013)

The ability of the 10-23 DNAzyme to specifically cleave RNA with high efficiency has fuelled expectation that this agent may have useful applications for targeted therapy. Here, we, for the first time, investigated the antitumor and radiosensitizing effects of a DNAzyme (DZ1) targeted to the Epstein-Barr virus (EBV)-LMP1 mRNA of nasopharyngeal carcinoma (NPC) in patients. Preclinical studies indicated that the DNAzyme was safe and well tolerated. A randomized and double-blind clinical study was conducted in 40 NPC patients who received DZ1 or saline intratumorally, in conjunction with radiation therapy. Tumor regression, patient survival, EBV DNA copy number and tumor microvascular permeability were assessed in a 3-month follow-up. The mean tumor regression rate at week 12 was significantly higher in DZ1 treated group than in the saline control group. Molecular imaging analysis showed that DZ1 impacted on tumor microvascular permeability as evidenced by a faster decline of the K(trans) in DZ1-treated patients. The percentage of the samples with undetectable level of EBV DNA copy in the DZ1 group was significantly higher than that in the control group. No adverse events that could be attributed to the DZ1 injection were observed in patients.
Terfenadine and Hepatitis
Authors: DOMINIQUE LARREY
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 October 1985Terfenadine and HepatitisDOMINIQUE LARREY, M.D., LAURENT PALAZZO, M.D., JEAN-PIERRE BENHAMOU, M.D.DOMINIQUE LARREY, M.D.Search for more papers by this author, LAURENT PALAZZO, M.D.Search for more papers by this author, JEAN-PIERRE BENHAMOU, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-103-4-634_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We write to report a case of acute hepatitis probably caused by terfenadine, an H1-receptor antagonist widely used as an antiallergic agent in Europe since 1982 and introduced in the United States in May 1985.On 15 September 1983, a 43-year-old woman started taking terfenadine, 60 mg/d, for treatment of recurrent urticaria. On 20 February 1984, she complained of asthenia and jaundice. She had no history of previous disease of the liver or biliary tract, had never received blood transfusion or blood products, and had no recent surgery. Clinical findings were normal except for jaundice. Her serum... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hôpital Beaujon 92118 Clichy France PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCetirizine-induced hepatotoxicity: case series and review of the literatureDRUG-INDUCED LIVER DISEASECinnarizine-induced cholestasisTerfenadine and risk of acute liver diseaseTerfenadine-induced cholestatic hepatitis 1 October 1985Volume 103, Issue 4Page: 634-634KeywordsBiliary systemBlood transfusionHepatitis ALiver diseasesSurgeryUrticaria Issue Published: 1 October 1985 PDF DownloadLoading ...