tbuckley/cabot-search huggingface dataset:
Abstract 2993: Impaired PARP1 DNA repair defines chemo-sensitivity in IDH1 mutant cell
Authors: Chunzhang Yang, Yanxin Lu, Yang Liu, Mark Gilbert, Jing Wu
Journal: Cancer Research (2019)

Abstract INTRODUCTION: Mutations in isocitrate dehydrogenase (IDH1/2) are the most prevalent genetic deficiency in lower grade gliomas. IDH-mutated in glioma exhibits better clinical outcomes with longer patient survival, as well as greater sensitivity to chemotherapy. In the present study, we explored the molecular mechanisms that determine the chemo-sensitivity in IDH1-mutated cells, and seek for potential therapeutic strategy by targeting PARP/BER DNA repair pathway. METHODS: We investigated transcriptomic profile from WHO grade II/III glioma based on their IDH1/2 mutation status. We established IDH1-mutated cells and investigated the alterations in nicotinamide adenine dinucleotide (NAD+), Poly (ADP-ribose) polymerase (PARP)-associated DNA repair and DNA damage in these cells in respond to temozolomide (TMZ). Moreover, we evaluated a PARP inhibitor olaparib and its synergistic effect on TMZ-associated cytotoxicity. RESULTS: Our results showed that the IDH1-mutated cells are more vulnerable to genotoxic agent, which recapitulate the disease phenotype in IDH1-mutated glioma. TMZ treatment resulted in over 20-fold increase of cell death in IDH1-mutated cells compared with wild type counterpart. IDH1-mutated cells exhibited over 1.3-fold DNA damage and over 1.42-fold cellular apoptosis under TMZ treatment. Mechanistically, IDH1-mutated cells exhibited compromised NAD+ metabolism, as well as concomitant PARP/BER DNA repair pathway. IDH1-mutated cells produced 83.8% less poly (ADP-ribose) polymer (pADPR), an important substrate for PARP-associated DNA repair, during TMZ treatment, suggesting their incompetence to maintain genomic integrity due to decreased availability of NAD+. Targeting the PARP-associated DNA repair pathway using olaparib, an FDA-approved PARP inhibitor, remarkably potentiated TMZ-induced cytotoxic effects by 2.16-fold in IDH1-mutated cells. CONCLUSION: Our findings demonstrate that metabolic defects in IDH1-mutated cells affect PARP-associated DNA repair pathway via NAD+ depletion, and therefore prompt the sensitivity to chemotherapies. Targeting PARP-associated DNA repair pathway suggests a novel therapeutic avenue for IDH1-mutated gliomas. Citation Format: Chunzhang Yang, Yanxin Lu, Yang Liu, Mark Gilbert, Jing Wu. Impaired PARP1 DNA repair defines chemo-sensitivity in IDH1 mutant cell [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2993.
Active Immunization
Authors: Geoffrey Edsall
Journal: New England Journal of Medicine (1949)

Pertussis Results Obtained with Vaccine Opinion regarding the efficacy of pertussis vaccine is still far from unanimous. Bell,6 in a recent review of the subject, stated that "health officers have sufficient evidence to permit the use of [pertussis vaccine]." Lewis174 sums up the conservative view, more widely held in England, that there is still a need for large-scale field trials, and that until these have been carried out no widespread campaign for whooping-cough inoculation in that country is justified. Parish175 similarly expresses the belief that the laboratory and clinical evidence to date do not prove the effectiveness of specific immunization . . .
Blocked beds.
Authors: F W Murphy
Journal: BMJ (1977)

In a cross-sectional survey of 325 surgical and orthopaedic beds 43 (16%) of the 265 occupied beds were filled by patients who had no medical need to be in an acute ward. They had been in hospital for a median time of 40 weeks up to the survey date. Of the 43 patients, 11 were awaiting transfer to a geriatric ward; 13 to community residential care; and seven to their homes. There was no plan for discharge or transfer for the remaining 12 (28%). Those "at risk" of becoming long-stay patients for social reasons on these wards were women, over 75, living alone or with one relative, who had been admitted to hospital in emergency with a fractured femur, head injury, or other trauma. Action necessary to reduce the number of social long-stay patients includes (a) changing attitudes to the solving of social case problems; (b) revising procedures of assessment and planning of future care; (c) improving teamwork and record keeping within the hospital and the community services; (d) providing a better balance of acute, medium and long-stay hospital beds; and (e) putting more resources into rehabilitation.
Author Index
Authors: M Abate, S Accordino, O Adeyi, Aonso De Araujo, A Agarwal, R Agarwal, L Agostinelli, G Aithal, M Alaibac, I Altorjay, V Carretta, S Caruso, G Casals, D Cassio, L Castera, E Caturelli, G Caviglia, M Cazzaniga, M Cela, F Cerini, L Chan, L Chang, V Chantarangkul, M Charlton, U Chatterji, Y Chawla, K Chayama, O Chazouillères, Y.-W Chen, A.-L Cheng, W Cheng, S Chevaliez, M Chiaramonte, R Chin, Y.-Y Chiou, F Chisari, C Cho, E Cholongitas, Y Chrétien, E Christensen, B Chua, C Davies, S Davies
Journal: Journal of Hepatology (2010)
Gastrointestinal System
Authors: H. A. Ziessman
Journal: Clinical Nuclear Medicine (2008)

Radionuclide methods are ideally suited for evaluation of gastrointestinal disease because of the functional nature of the methodology. Many gastrointestinal radionuclide tests have stood the test of time. For decades, the gastric emptying study has been the gold standard for quantification of gastric motility. Motility studies of the esophagus and intestinal tract, although less commonly requested, provide valuable diagnostic and therapeutic information at many centers. The gastrointestinal bleeding study can noninvasively localize a site of active hemorrhage and guides specific intervention and therapy. Meckel's scan can detect ectopic gastric mucosa as a cause of rectal bleeding in children, and radionuclide methods confirm gastroesophageal reflux with high sensitivity, particularly in neonates and young children.
Affiliation and Reprint Address Omitted.
Journal: JAMA (1992)

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
741 A NOVEL AND VALIDATED PROGNOSTIC INDEX IN HEPATOCELLULAR CARCINOMA: THE INFLAMMATION BASED INDEX (IBI)
Authors: D.J. Pinato, J. Stebbing, M. Ishizuka, S.A. Khan, H.S. Wasan, B.V. North, K. Kubota, R. Sharma
Journal: Journal of Hepatology (2012)
Dysregulation of aquaporin-1 in human CCA cells triggers epithelial-mesenchymal transition
Authors: César Gaspari, Seth Richard, Javier Vaquero, Ander Arbelaiz, Marie Vallette, Aalekhya Biswas, Julieta Marrone, Raúl Marinelli, Laura Fouassier, Sergio Gradilone
Journal: Journal of Hepatology (2020)
Suprasternal ultrasonography
Authors: B. B. Goldberg
Journal: JAMA (1971)

Ultrasound has been used to measure the diameters of the aortic arch, right pulmonary artery, and left atrium. This new method is described in detail. The transducer is placed in the suprasternal region and the ultrasonic beam is directed caudad. Cadaver and clinical experiments have confirmed the reliability of the ultrasonic results. Suprasternal ultrasonic readings were obtained on 100 patients, including 52 normals, 18 with hypertensive cardiovascular disease, 24 with rheumatic heart disease, and 6 with congenital heart disease. Excellent correlation between the ultrasonic and angiographic lumen measurements in both healthy and diseased subjects was shown.
The Goulstonian Lectures ON THE INFLUENCE OF PREGNANCY UPON CERTAIN MEDICAL DISEASES, AND OF CERTAIN MEDICAL DISEASES UPON PREGNANCY: Delivered before the Royal College of Physicians of London
Authors: H. French
Journal: BMJ (1908)

June 7th he complained of pain over, the right lobe of the liver.This continued till, on June gtb, after taking a little nourishment, he suddenly collapeed and died in a few.minutes. Necropyy.At apost-mortem examination on June llth-forly hours after death-tbe following faots were noted: The wound was healthy and well shut off by adhesions, and neither in loin nor pelvis was there any pus.The peritoneum itself was normal, Cut its cavity contained a quantity of serous fluid mixed with pus.A number of -small abscesses were found in the substance of the right lobe of the liver, and also two larger ones, which had communicated, and by projecting on the right surfaes of the lobe had caused the abdominal pain complained of from June 7th, and by their rupture into the general paretoneal cavity had oaused sudden death.The left lobe and gall bladder were normal.The portal vein was normal, and had no communication with the abscesses, so that it was a lymphatic infection of the liver.The interesting points of this case are: 1.That, though the patient had his first rigor on the night of April 14th, It was not till the evening of the 17th that the first physical sign was noticed, and then only a slight one.2. That the antistreptococcus serum did no apparent good, whereas the quinine certainly appeared to lessen the frequency of the rigors.3. That the right lobe of the liver was affected, but not the left.ti OiulTt5tOim 3trturts
Pulmonary Function in Adults with Intracardiac Septal Defect
Journal: JAMA (1963)

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Malignant Melanoma
Authors: Hiram C. Polk
Journal: JAMA (1980)

<i>Malignant Melanoma</i>is a fine monograph authored by Alfred Kopf and his colleagues in dermatology at the New York University School of Medicine and with the special input of A. Bernard Ackerman of the Departments of Dermatology and Pathology. The book is an expansion of an extensive review article previously published in the<i>Journal of Dermatologic Surgery and Oncology</i>. In general, the book is well produced, with clearly readable type, some excellent photographs of melanomatous lesions, and fine photomicrographs in both black and white and color. The 22 chapters review melanoma in great breadth. Virtually every common and exotic manifestation of melanoma is discussed in detail, usually succinctly with carefully developed and valid conclusions. The section on histopathology of cutaneous melanoma occupies more than half the book. It is carefully and exhaustively done; it is perhaps this weighting of effort that is the book's only notable detraction. Staging, prognosis, biopsy,
CARBOLIC ACID GANGRENE.
Journal: JAMA (1900)

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Table of Contents
Authors: Vanesa Bijol, Youssef Farag, David Harris, Adeera Levin, Ajay Singh, Kenar Jhaveri, Luca Perico, Ariela Benigni, V Knoers, Kirsten Renkema, Anatália Labilloy, Ora Weisz, Brooke Chambers, Rebecca Wingert, Craig Langman, Carmel Hawley, Elaine Pascoe, Lesley Inker, Andrew Levey, Michaël Van Baar, Rosalie Scholtes, Daniël Van Raalte, Goce Spasovski, Merita Rroji, Evgueniy Vazelov, Nikolina Jukic, Vladimir Tesar, Marina Ratkovic, Adrian Covic, Radomir Naumovic, Halima Resic, Rumeyza Kazancioglu, Aspasia Pefanis, Francesco Ierino, James Murphy, Peter Cowan, Jonatan Barrera-Chimal, Sophie Girerd, Frederic Jaisser, Rannar Airik, Merlin Airik, Markus Schueler, Carlton Bates, Friedhelm Hildebrandt, Ivan Morace, Robert Pilz, Giuseppina Federico, Richard Jennemann, Damir Krunic, Viola Nordström, Johanna Von Gerichten, Christian Marsching, Ina Schießl, Johannes Müthing, Christian Wunder, Ludger Johannes, Roger Sandhoff, Hermann-Josef Gröne
Journal: Kidney International (2019)
Journal summary
Journal: Annals of the Rheumatic Diseases (1990)

LEADERHepatitis and non-steroidal anti-inflammatory drugs p 489 We have long become used to the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the gut, but this leader comes as a reminder to us that it is not only upon the gastrointestinal tract that the effects exert their action.It is on the liver too that NSAIDs (including aspirin) may exert an adverse action.Fortunately this is usually reversible and mild, though in the case of benoxaprofen it proved not to be so.Though rare, nevertheless this effect is important.
Overexpression of TOSO in CLL Is Triggered by B-Cell Receptor Signaling and Associated with Progressive Disease.
Authors: Christian P Pallasch, Alexandra Schulz, Nadine Kutsch, Janine Schwamb, Susanne Hagist, Claudia Wickenhauser, Alfred Ultsch, Hamid Kashkar, Michael Hallek, Clemens-Martin Wendtner
Journal: Blood (2008)
Mitochondrial DNA: A New Frontier in Acquired and Inborn Gene Defects
Journal: JAMA (1991)

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
Handbuch der Therapie: Therapie des praktischen Arztes in Einzeldarstellungen
Journal: JAMA (1949)

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
ACTR-10. PHASE 0 TRIAL OF CERITINIB IN BRAIN METASTASES AND RECURRENT GLIOBLASTOMA
Authors: Roberto Fiorelli, Jing Li, Xun Bao, Alanna DeRogatis, Chelsea Pennington-Krygier, Seongho Kim, Shwetal Mehta, Nader Sanai
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Ceritinib is an orally bioavailable, small molecule inhibitor for ALK/IGFR1/FAK, which are highly expressed in glioblastoma and brain metastases. Preclinical and clinical reports suggest ceritinib activity in central nervous system (CNS) malignancies, yet there is no direct evidence in patients. This study assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of ceritinib in brain metastases and recurrent glioblastoma patients. METHODS Ten patients with brain metastases (n=3) or glioblastoma (n=7) exhibiting high expression of pSTAT5b/pFAK/pIGFR1 were treated with 10 days of oral ceritinib (750 mg daily) prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at ~ 4 and 24 h following the last dose. Total and unbound drug concentrations were determined using LC-MS/MS. PD response was assessed by immunohistochemical analysis of pALK, pFAK, pIGFR1, and pIRS1 staining in treated tumor and matched archival tissues. RESULTS Ceritinib was highly bound to human plasma protein (median fraction unbound (Fu), 1.4%) and to brain tumor tissue (median Fu, 0.073% and 0.14% in enhancing and non-enhancing regions respectively). There was a large interindividual variability in drug CNS penetration, with the median unbound concentrations in enhancing, non-enhancing, and CSF of 0.040, 0.006, and 0.012 µM, respectively. The median unbound tumor-to-plasma ratio was 2.44 and 0.33 in enhancing and non-enhancing areas, respectively. In one brain metastasis patient, drug binding to enhancing tumor was significantly lower (Fu, 1.62%), resulting in a higher unbound drug tumor and CSF concentration as compared to all other patients. In all patients, no pharmacodynamic response was detected in sampled tumor tissue. CONCLUSION Ceritinib is highly bound to plasma proteins and tumor tissues. Unbound drug concentrations in brain metastasis and glioblastoma appear insufficient for target modulation. Despite recent reports of clinical response, our findings suggest no role for ceritinib in treating glioblastoma and an unfavorable profile for brain metastases.
Editorial: Treatment of herpesvirus infections
Authors: W. E. Rawls
Journal: JAMA (1976)

Members of the herpesvirus group that infect man include herpes simplex virus types 1 and 2, cytomegalovirus, varicellazoster virus, and Epstein-Barr virus. Infections with these viruses are often asymptomatic or associated with a mild self-limiting illness. After primary infections, the viruses persist in a latent form. Recurrent lesions are caused by reactivation of the latent viruses, and recurrent lesions are especially common with the herpes simplex viruses. The recurrent lesions are usually localized and of limited duration; however, they may produce not only physical discomfort but considerable psychological distress, especially among patients with genital herpes. Occasionally, infections by these viruses are severe, as exemplified in herpes simplex encephalitis and by infections in the newborn. Severe infections are also observed in immunocompromised patients. Finally, evidence suggests that members of this group of viruses may be oncogenic. Thus, the need for effective methods of treating infections by members of the herpesvirus group
WASHINGTON
Journal: JAMA (1967)

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