tbuckley/cabot-search huggingface dataset:
Generation of Novel AAV Variants by Directed Evolution for Improved CFTR Delivery to Human Ciliated Airway Epithelium
Authors: Wuping Li, Liqun Zhang, Jarrod S Johnson, Wu Zhijian, Joshua C Grieger, Xiao Ping-Jie, Lauren M Drouin, Mavis Agbandje-McKenna, Raymond J Pickles, R Jude Samulski
Journal: Molecular Therapy (2009)

Recombinant adeno-associated virus (AAV) vectors expressing the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been used to deliver CFTR to the airway epithelium of cystic fibrosis (CF) patients. However, no significant CFTR function has been demonstrated likely due to low transduction efficiencies of the AAV vectors. To improve AAV transduction efficiency for human airway epithelium (HAE), we generated a chimeric AAV library and performed directed evolution of AAV on an in vitro model of human ciliated airway epithelium. Two independent and novel AAV variants were identified that contained capsid components from AAV-1, AAV-6, and/or AAV-9. The transduction efficiencies of the two novel AAV variants for human ciliated airway epithelium were three times higher than that for AAV-6. The novel variants were then used to deliver CFTR to ciliated airway epithelium from CF patients. Here we show that our novel AAV variants, but not the parental, AAV provide sufficient CFTR delivery to correct the chloride ion transport defect to ~25% levels measured in non-CF cells. These results suggest that directed evolution of AAV on relevant in vitro models will enable further improvements in CFTR gene transfer efficiency and the development of an efficacious and safe gene transfer vector for CF lung disease. Recombinant adeno-associated virus (AAV) vectors expressing the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been used to deliver CFTR to the airway epithelium of cystic fibrosis (CF) patients. However, no significant CFTR function has been demonstrated likely due to low transduction efficiencies of the AAV vectors. To improve AAV transduction efficiency for human airway epithelium (HAE), we generated a chimeric AAV library and performed directed evolution of AAV on an in vitro model of human ciliated airway epithelium. Two independent and novel AAV variants were identified that contained capsid components from AAV-1, AAV-6, and/or AAV-9. The transduction efficiencies of the two novel AAV variants for human ciliated airway epithelium were three times higher than that for AAV-6. The novel variants were then used to deliver CFTR to ciliated airway epithelium from CF patients. Here we show that our novel AAV variants, but not the parental, AAV provide sufficient CFTR delivery to correct the chloride ion transport defect to ~25% levels measured in non-CF cells. These results suggest that directed evolution of AAV on relevant in vitro models will enable further improvements in CFTR gene transfer efficiency and the development of an efficacious and safe gene transfer vector for CF lung disease.
miR-34b Targets Cyclic AMP–Responsive Element Binding Protein in Acute Myeloid Leukemia
Authors: Martina Pigazzi, Elena Manara, Emma Baron, Giuseppe Basso
Journal: Cancer Research (2009)

The cyclic AMP-responsive element binding protein (CREB) is documented to be overexpressed in leukemia, but the underlying mechanism remains unknown. Here, microRNAs (miRNA), which act as negative regulators of gene expression principally through translational repression, are investigated for the mediation of high CREB protein levels. A series of miRNAs that target CREB were identified. Real-time quantitative PCR revealed that miR-34b was expressed significantly less in myeloid cell lines, previously known for high CREB protein levels. Exogenous miR-34b expression was induced, and results revealed a direct interaction with the CREB 3'-untranslated region, with the consequent reduction of the CREB protein levels in vitro. miR-34b restored expression caused cell cycle abnormalities, reduced anchorage-independent growth, and altered CREB target gene expression, suggesting its suppressor potential. Using reverse-phase protein array, CREB target proteins (BCL-2, cyclin A1, cyclin B1, cyclin D, nuclear factor-kappaB, Janus-activated kinase 1, and signal transducer and activator of transcription 3), as well as many downstream protein kinases and cell survival signaling pathways (AKT/mammalian target of rapamycin and extracellular signal-regulated kinase) usually elicited by CREB, were observed to have decreased. The miR-34b/miR-34c promoter was shown to be methylated in the leukemia cell lines used. This epigenetic regulation should control the observed miR-34b expression levels to maintain the CREB protein overexpressed. In addition, the inverse correlation between miR-34b and CREB expression was found in a cohort of 78 pediatric patients at diagnosis of acute myeloid leukemia, supporting this relationship in vivo. Our results identify a direct miR-34b target gene, provide a possible mechanism for CREB overexpression, and provide new information about myeloid transformation and therapeutic strategies.
European Society of Gastrointestinal Endoscopy (ESGE) guideline: the use of electrosurgical units
Authors: J. Rey, U. Beilenhoff, C. Neumann, J. Dumonceau
Journal: Endoscopy (2010)

Electrosurgery is used in the majority of endoscopic therapeutic procedures. An understanding of the fundamental electrosurgical principles and various settings available on electrosurgical units is essential for the safe and effective use of electrosurgery during endoscopy. The aims of these technical guidelines are to: (1) expose physical principles relevant to the understanding of electrosurgery during endoscopy; (2) describe and provide practical recommendations regarding electrosurgical units that are commonly in use; (3) discuss the clinical relevance of technologies recently implemented in newer electrosurgical units; and (4) review factors relevant to commonly performed therapeutic procedures, including polypectomy, sphincterotomy, contact thermal hemostasis, and argon plasma coagulation.
A STUDY OF RESULTS IN HOSPITAL TREATMENT OF DRUG ADDICTIONS
Authors: ROBERT G. KNIGHT, CURTIS T. PROUT
Journal: American Journal of Psychiatry (1951)

1. A study has been made of 75 patients admitted to the New York Hospital—Westchester Division between January 1, 1930, and January 1, 1950, for the treatment of drug addiction. 2. The primary drug of addiction was morphine in 34, barbiturates in 24, and other drugs such as heroin, dilaudid, codeine, and demerol in 17 cases. 3. A statistical review of hereditary and environmental factors is presented. 4. Methods of hospital management have been discussed. 5. A plan for a standardized psychological survey has been presented. 6. Follow-up studies revealed that 15 have remained abstinent following hospitalization for 1 to 14 years and that, as a result of the treatment, 12 more are managing better, indicating that about 36% seem to have been benefited.
Topical mechlorethamine therapy for mycosis fungoides
Authors: NORMAN M. PRICE, VICTOR S. CONSTANTINE, RICHARD T. HOPPE, ZVI Y. FUKS, EUGENE M. FARBER
Journal: British Journal of Dermatology (1977)

Patients with limited skin involvement by mycosis fungoides were treated with daily topical mechlorethamine. Seven of thirteen patients had a complete remission of diseases. Six of these seven experienced a contact dermatitis and four underwent a successful topical desensitization programme. The possible beneficial therapeutic effects of developing a contact allergy are discussed.
Schonlein-Henoch Syndrome After Insect Bite
Authors: G. Sharan, R. K. Anand, K. P. Sinha
Journal: BMJ (1966)

In the available literature only one case of Sch6nlein-Henoch syndrome occurring after an insect bite has so far been published (Burke and Jellinek, 1954).The present case is of added interest because of the patient's poor response to steroids.In Burke and Jellinek's case the response was said to be dramatic. CASE REPORTA 10-year-old girl was bitten by an insect on her right leg (see Fig.).Two days later, according to her parents, she was found to have urticaria on the dorsum of both feet, pain in the abdomen with mucus in the stool, and nausea and vomiting.There was no history of a sore throat or of allergy in the child or in the family, nor had any drug been given before the present illness.H i . . ., . . .~~~~~~~~.. . . .
Long-term Survival Following Bacteremia or Fungemia
Authors: Leonard Leibovici
Journal: JAMA (1995)

<h3>Objective.</h3> —To delineate long-term survival after an episode of bacteremia or fungemia and risk factors for mortality. <h3>Design.</h3> —Cohort study. <h3>Setting.</h3> —A 900-bed university hospital in Israel. <h3>Patients.</h3> —Study group comprising 1991 patients 18 years of age or older in whom bacteremia or fungemia were detected between March 1988 and October 1992, and a control group comprising 1991 inpatients without any infectious diseases, matched for age, sex, department, date of admission, and underlying disorders. <h3>Interventions.</h3> —None. <h3>Measurements.</h3> —Interval from the date of the first positive blood culture (study group) or from date of the identical hospital day (in the matched control patient) to the date of death as recorded in the Israeli National Population registry or, if alive, to June 1, 1994. <h3>Results.</h3> —The median age of patients was 72 years. In the study group, the mortality rate was 26% at 1 month, 43% at 6 months, 48% at 1 year, and 63% at 4 years, and the median survival was 16.2 months. In the control group, the mortality rate was 7% at 1 month, 27% at 1 year, and 42% at 4 years, and the median survival was greater than 75 months (<i>P</i>&lt;.001). Factors significantly and independently associated with mortality in bacteremic patients were functional class (median survival, 0.5 month in bedridden patients), septic shock (median survival, 0.2 month), serum albumin (median survival, 1.1 months in the lowest quartile), serum creatinine (median survival, 2.9 months in the highest quartile), age (median survival, 2.9 months in the highest quartile [age &gt;80 years]), inappropriate empirical antibiotic treatment (median survival, 4.9 months), nosocomial infection (median survival, 9.6 months), and malignancy (median survival, 2.4 months). <h3>Conclusions.</h3> —Bacteremia is associated with high short-term mortality, but also a sign of severely curtailed long-term prognosis, especially in patients with low functional capacity, low serum albumin, high serum creatinine, nosocomial infections, malignancy, inappropriate antimicrobial treatment, and septic shock and in elderly patients. (<i>JAMA</i>. 1995;274:807-812)
A comparison of the results of renal transplantation from non–heart-beating, conventional cadaveric, and living donors
Authors: Michael L. Nicholson, Matthew S. Metcalfe, Steven A. White, Julian R. Waller, Tahir M. Doughman, Terry Horsburgh, John Feehally, Susan J. Carr, Peter S. Veitch
Journal: Kidney International (2000)
Absolute granulocyte, lymphocyte, and moncyte counts. Useful determinants of prognosis for patients with metastatic cancer of the stomach
Authors: H. W. Bruckner
Journal: JAMA (1982)

Pretreatment absolute granulocyte (&lt;6,000/cu mm), lymphocyte (&gt;1,500/cu mm), and monocyte (300 to 900/cu mm) counts are three independent indicators of good prognosis for patients with metastatic gastric cancer. These tests improve the prediction of survival significantly compared with estimates based on ambulatory status alone. If the patient is completely ambulatory, median survival (MS) is 27.6 weeks, and it improves further to 37.6 weeks if results of two hematology tests indicate a good prognosis. If the patient is partially ambulatory, MS is 16.2 weeks; however, if results of two blood tests indicate a good prognosis, MS is 25.7 weeks, and if two tests indicate a poor prognosis, MS is only 11.1 weeks. The model corrected a false assessment of a poor prognosis for 56% of all patients. (<i>JAMA</i>1982;247:1004-1006)
Acute Hemorrhagic Pancreatitis Associated with Administration of Chlorthalidone
Authors: Martin F. Jones, John R. Caldwell
Journal: New England Journal of Medicine (1962)

CHLOROTHIAZIDE, since its introduction in 1957, has been followed by a large number of congeners. These agents are benzothiadiazine derivatives which pharmacologically act in the same manner in that they inhibit the reabsorption of sodium by the renal tubules and increase excretion of sodium chloride and potassium.1 , 2 Some uncommon toxic manifestations have been reported as a result of their use. Most of the reports implicate chlorothiazide or hydrochlorothiazide mainly because these compounds were among the first to appear on the market and enjoy a much wider use than the others. The uncommonly reported toxic manifestations have included skin rash, gastrointestinal . . .
Reply from Authors re: Alexandre M. Mottrie. The Introduction of Robot-Assisted Surgery in Urologic Practice: Why Is It So Difficult? Eur Urol 2010;57:747–9 and Manfred P. Wirth, Michael Froehner. Robot-Assisted Radical Prostatectomy: The New Gold Standard? Eur Urol 2010;57:750–1
Authors: Declan G. Murphy
Journal: European Urology (2010)
Cell Phone Activation and Brain Glucose Metabolism—Reply
Authors: Nora D. Volkow
Journal: JAMA (2011)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
An Increased Expression of Cysteinyl Leukotriene 2 Receptor in Colorectal Adenocarcinomas Correlates with High Differentiation
Authors: Cecilia Magnusson, Roy Ehrnström, Jørgen Olsen, Anita Sjölander
Journal: Cancer Research (2007)

Abstract Increased levels of inflammatory mediators such as cysteinyl leukotrienes (CysLT) have been found in and around tumors. These data, along with our previous observation that the G-protein–coupled receptor CysLT1R, which signals survival and proliferation, is up-regulated in colon cancer, suggest an important role for CysLT1R in tumor development. The objective of this study was to examine the expression and function of the low-affinity CysLT2 receptor (CysLT2R) in colon cancer. We found lower expression levels of CysLT2R compared with CysLT1R in cancer cell lines as well as clinical tumor material. Interestingly, CysLT2R, like CysLT1R, was found to be one of few G-protein–coupled receptors that are located both at the plasma membrane and the nuclear membrane. No effect of CysLT2R signaling on cell proliferation was observed, nor was there a correlation between CysLT2R and different proliferation markers such as Ki-67 and cyclooxygenase-2 in the tumor material. Instead, we found that activation of this receptor in colon cancer cells led to cellular differentiation similar to the effects of butyrate treatment. In accordance with this finding, we found that reduced expression of CysLT2R in colon cancer was associated with poor prognosis. We report the novel finding that CysLT2R signaling leads to terminal differentiation of colon carcinoma cells and growth inhibition, and that its expression is relatively high in less malignant forms of colon cancer. These data suggest that the balance between these two receptors is important for tumor progression and disease outcome. [Cancer Res 2007;67(19):9190–8]
Adult Clinical Cardiology Self-Assessment Program: ACCSAP 2000
Authors: Craig H. Scott
Journal: Annals of Internal Medicine (2000)

Medical Writings: Book Notes1 February 2000Adult Clinical Cardiology Self-Assessment Program: ACCSAP 2000Craig H. Scott, MDCraig H. Scott, MDFrom University of Pennsylvania, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-3-200002010-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Conti CR, Lewis RP, eds. Bethesda, MD: American Coll of Cardiology; 2000. Single-user price, $345.00. Order phone 800-253-4636, ext. 694.Field of medicine: Adult cardiovascular medicine.Format: CD-ROM software and printed booklets.Minimum system requirements: PC: Windows 95, 100-MHz Pentium with 32 Mb of RAM, 20 Mb of free hard disk space, 16-bit sound card, 800 × 600 resolution monitor with 256 colors, and 4× CD-ROM. Macintosh: System 8, PowerPC with 16 Mb of RAM, 20 Mb of free hard disk space, 800 × 600 resolution monitor with thousands of colors, 4× CD-ROM, and QuickTime 3.0.Audience: Specialists in adult ... Author, Article, and Disclosure InformationAffiliations: From University of Pennsylvania, Philadelphia, Pennsylvania. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 2000Volume 132, Issue 3Page: 252KeywordsCardiology and cardiovascular diseasesCardiovascular diseasesCatheterizationElectrocardiographyMedical educationSoftware tools ePublished: 15 August 2000 Issue Published: 1 February 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A new prognostic model for hepatocellular carcinoma based on total tumor volume: The Taipei Integrated Scoring system
Authors: Chia-Yang Hsu, Yi-Hsiang Huang, Cheng-Yuan Hsia, Chien-Wei Su, Han-Chieh Lin, Che-Chuan Loong, Yi-You Chiou, Jen-Huey Chiang, Pui-Ching Lee, Teh-Ia Huo, Shou-Dong Lee
Journal: Journal of Hepatology (2010)
Personal Physician and Moonlighting
Authors: P. W. Van Metre
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Personal Physician, so ably described by Dr. Zanof in five-syllable words, should also be able to resist Lucifer, the Prince of Deceivers, who assures the gullible that life consists in the abundance of things one possesses, the abundance being in riches, not wisdom. Today's young interns and residents see doctor-devotees of this devilish doctrine all about them and are tempted to "moonlight" to acquire their abundance.
Why quantum probability does not explain the conjunction fallacy
Authors: Katya Tentori, Vincenzo Crupi
Journal: Behavioral and Brain Sciences (2013)

Abstract We agree with Pothos &amp; Busemeyer (P&amp;B) that formal tools can be fruitfully employed to model human judgment under uncertainty, including well-known departures from principles of classical probability. However, existing findings either contradict P&amp;B's quantum probability approach or support it to a limited extent. The conjunction fallacy serves as a key illustration of both kinds of problems.
Could the "real" preconditioning mechanism please stand up? (or, a polyplanic platitude to preconditioning)
Authors: A. Banerjee
Journal: Cardiovascular Research (1994)

Journal Article Could the “real” preconditioning mechanism please stand up? (or, a polyplanic platitude to preconditioning) Get access Anirban Banerjee Anirban Banerjee Associate Professor Department of Surgery, University of Colorado Health Sciences Center, Denver, CO, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 12, December 1994, Pages 1872–1873, https://doi.org/10.1093/cvr/28.12.1872 Published: 01 December 1994
Did sculpting give artists a health advantage before antibiotics?
Authors: Roger Dobson
Journal: BMJ (2007)

A study has shown that great sculptors live longer than great painters, and the reason may lie in the greater level of exertion needed for the first job compared with the second.

Old master sculptors lived on average three years longer than old master painters, and the physical work involved may have helped boost the ability of their immune systems to fight off infections in the age before antibiotics, researchers say ( Age and Ageing 2007 Dec 3 doi: 10.1093/ageing/afm172).

In the study, the authors created a database of European old master painters and sculptors, excluding those who had lived in the 20th century. Although Michelangelo was …
Cocaine Deaths Reported for Century or More
Authors: Teri Randall
Journal: JAMA (1992)

THE COCAINE craze that swung through Europe and the United States during the turn of the century has come full circle in recent decades. It is uglier and deadlier this time around. Yet to those who study medical history, it is strangely familiar, a repetition of the past that holds few surprises. "We are seeing today a lot of problems that were seen 100 years ago. Medical, political, and social, they are repeating," says Steven Karch, MD, research director of the Trauma Center at the University Medical Center of Southern Nevada, Las Vegas. Karch, a cardiac researcher, became interested in cocaine cardiotoxicity because it appears to be mediated by the same hormonal mechanisms involved in severe stress and resuscitation. He has also written on the history of cocaine toxicity (<i>Hum Pathol</i>. 1989;20:1037-1039), and last December spoke at the Third National Conference on Death and Injury Investigation in Wichita, Kan. "Contrary
Dying matters: let's talk about it
Authors: J. E. Seymour, J. French, E. Richardson
Journal: BMJ (2010)

As death has become less common in our daily lives, it has become harder to consider our own mortality or that of those close to us. Lack of openness about death has negative consequences for the quality of care provided to the dying and bereaved. Eradicating ignorance about what can be achieved with modern palliative care and encouraging dialogue about end of life care issues are important means of changing attitudes.