tbuckley/cabot-search huggingface dataset:
Abstract 3774: Hyperthermia treatment overcomes temozolomide resistance in glioma cells by downregulating <i>MGMT</i> expression and increasing temozolomide uptake
Authors: Chen-Ting Lee, Aaron Blackley, Chelsea Landon, Ivan Spasojevic, John P. Kirkpatrick, Mark W. Dewhirst
Journal: Cancer Research (2014)

Abstract Glioblastoma multiforme (GBM) is the most common and malignant brain tumor. Current standard treatment for GBM following maximum safe resection includes temozolomide (TMZ) with concurrent radiotherapy. Despite the improvement of survival by TMZ and radiation, the overall prognosis remains poor for GBM patients. This is partially attributed to drug resistance. Expression of DNA repair protein O6-methylguanine methyltransferase (MGMT) in gliomas confers TMZ resistance and a worse prognosis. Therefore, development of novel therapy to suppress MGMT expression and overcome TMZ resistance is highly desired. Hyperthermia has been shown to increase TMZ sensitivity in melanoma and this provides a good rationale to evaluate whether hyperthermia overcomes TMZ resistance in glioblastoma cells. In this study, we investigated the effect of hyperthermia treatment (43 °C) on TMZ sensitivity of four human glioblastoma cell lines using clonogenic assays. Our results showed that hyperthermia treatment increased TMZ-induced cell death in TMZ-resistant glioma cells, but had no additional beneficial effect in the TMZ-sensitive cells. Hyperthermia in combination with radiation further overcame TMZ resistance. To study the molecular targets, we found that hyperthermia downregulated MGMT expression through increasing proteasome-mediated MGMT degradation, which can be reversed by the proteasome inhibitor bortezomib. Hyperthermia had no effects on p53 expression and MGMT promoter methylation which was responsible for MGMT gene silencing. In addition, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed an increase of TMZ and its downstream product 5-aminoimidazole-4-carboxamide (AIC) in hyperthermia-treated cells, indicating an increase of TMZ drug uptake and breakdown. In conclusion, these results suggest that hyperthermia overcomes MGMT-mediated resistance of glioblastoma cell lines to TMZ and increases TMZ drug uptake. This study suggests a potential benefit of using hyperthermia in the treatment of GBM, particularly those with more adverse prognosis. This work was supported by Debrule Research Fund. Citation Format: Chen-Ting Lee, Aaron Blackley, Chelsea Landon, Ivan Spasojevic, John P. Kirkpatrick, Mark W. Dewhirst. Hyperthermia treatment overcomes temozolomide resistance in glioma cells by downregulating MGMT expression and increasing temozolomide uptake. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3774. doi:10.1158/1538-7445.AM2014-3774
Analysis of Point Mutations in an Ultraviolet-irradiated Shuttle Vector Plasmid Propagated in Cells from Japanese Xeroderma Pigmentosum Patients in Complementation Groups A and F
Authors: Takashi Yagi, Junko Tatsumi-Miyajima, Mayumi Sato, Kenneth H. Kraemer, Hiraku Takebe
Journal: Cancer Research (1991)

Abstract  To assess the contribution to mutagenesis by human DNA repair defects, a UV-treated shuttle vector plasmid, pZ189, was passed through fibroblasts derived from Japanese xeroderma pigmentosum (XP) patients in two different DNA repair complementation groups (A and F). Patients with XP have clinical and cellular UV hypersensitivity, increased frequency of skin cancer, and defects in DNA repair. The XP DNA repair defects represented by complementation groups A (XP-A) and F (XP-F) are more common in Japan than in Europe or the United States. In comparison to results with DNA repair-proficient human cells (WI38-VA13), UV-treated pZ189 passed through the XP-A [XP2OS(SV)] or XP-F [XP2YO(SV)] cells showed fewer surviving plasmids (XP-A less than XP-F) and a higher frequency of mutated plasmids (XP-A greater than XP-F). Base sequence analysis of more than 200 mutated plasmids showed the major type of base substitution mutation to be the G:C → A:T transition with all three cell lines. The XP-A and XP-F cells revealed a higher frequency of G:C → A:T transitions and a lower frequency of transversions among plasmids with single or tandem mutations and a lower frequency of plasmids with multiple point mutations compared to the normal line. The spectrum of mutations in pZ189 with the XP-A cells was similar to that with the XP-F cells. Seventy-six to 91% of the single base substitution mutations occurred at G:C base pairs in which the 5′-neighboring base of the cytosine was thymine or cytosine. These studies indicate that the DNA repair defects in Japanese XP patients in complementation groups A and F result in different frequencies of plasmid survival and mutagenesis but in similar types of mutagenic abnormalities despite marked differences in clinical features. These results, together with comparable studies from United States patients in XP complementation groups A and D, suggest that G:C → A:T somatic mutations may be important in the generation of human skin cancer by UV radiation.
A role for protein arginine methyltransferase 5 (PRMT5) in the mechanism of novel anticancer agent, AS1411.
Authors: Yun Teng, Paula J. Bates
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5507 

AS1411 (formerly AGRO100) is a guanosine-rich phosphodiester oligodeoxynucleotide that is currently being tested in a Phase I clinical trial for the treatment of advanced cancer. This agent has a novel mechanism of action that involves binding to nucleolin, a multifunctional protein that is expressed abnormally by cancer cells. Binding of AS1411 to nucleolin is thought to alter the molecular interactions of nucleolin, which modulates nucleolin function and leads to antiproliferative effects. The purpose of this study was to identify nucleolin-binding proteins whose interactions with nucleolin are perturbed in AS1411-treated cancer cells. The nucleolin complex was isolated by immunoprecipitation (IP) from human prostate cancer DU145 cells. Several nucleolin-interacting proteins, including protein arginine methyltransferase 5 (PRMT5), were identified by MALDI-TOF-mass spectrometry. PRMT5 is a Type II arginine methyltransferase (makes symmetrical dimethylarginine modifications) that has been implicated in the repression of certain tumor suppressor genes. To determine if AS1411 affects the nucleolin-PRMT5 interaction, we compared nucleolin-associated proteins from untreated, AS1411-treated and control oligonucleotide (CRO)-treated DU145 cells using anti-nucleolin IP. The results clearly showed altered interactions between PRMT5 and nucleolin in AS1411-treated cells. Specifically, the nucleolin-PRMT5 interaction was decreased in the nucleus, but increased in the cytoplasm. Further, we compared the activity of PRMT5 and other protein arginine methyltransferases by determining the level of dimethylated arginine (DMA) methylation in treated and untreated DU145 cells using antibodies that specifically recognize symmetrical DMA (sDMA)-containing peptides or asymmetrical DMA (aDMA)-containing peptides. The recognition patterns are distinct but partially overlap as some proteins are both recognized by these antibodies. The results showed that AS1411 treatment resulted in altered levels of sDMA modification, which were in accord with changes in its interactions with nucleolin. To determine if nucleolin is a substrate for methylation by PRMT5 in DU145 cells, we used anti-sDMA antibodies for co-IP. The sDMA-modified nucleolin was found in both nuclear and cytoplasmic extracts and its distribution was altered in AS1411-treated cells. Finally, we examined the expression of selected genes (including the ST7 tumor suppressor) that are repressed by PRMT5 and found a significant increase in AS1411-treated cells, consistent with the decreased nuclear activity of PRMT5. We conclude from our studies that nucleolin is a novel substrate and partner for PRMT5. Furthermore, we have found that a nucleolin-targeted anticancer agent, AS1411, disrupts the specific molecular interactions between nucleolin and PRMT5, which leads to altered distribution and activity of PRMT5.
Abstract 2685: Assessment of Myocardial Perfusion With Stress-Contrast Echocardiography in Diabetics
Authors: Constadina Aggeli, Georgios Giannopoulos, Georgios Roussakis, Euaggelia Christoforatou, Georgios Marinos, Nikolaos Ioakeimidis, Christos Kokkinakis, Christodoulos Stefanadis
Journal: Circulation (2007)

Background and purpose: The combination of myocardial contrast echocardiography with dobutamine-atropine stress echocardiography has shown promising results in the diagnostic approach of coronary heart disease (CHD). However, its diagnostic value in specific patient populations has not been clearly specified. The aim of the present study was to assess the value of stress contrast echocardiography (SCE) in diagnosing significant coronary heart disease in diabetic versus non-diabetic patients. Methods: 127 individuals (60 males, 62±9.8 years old) with no known history of CHD, among which 59 patients with Type 2 diabetes mellitus, were submitted to stress echocardiography (four-stage dobutamine protocol 10 – 40 mcg/kg/min, with use of atropine as required to reach 90% of age-adjusted target heart rate), combined with intravenous contrast use to perform myocardial contrast echocardiography. New or worsening wall motion abnormalities during stress or reversible perfusion defects in &gt;2 contiguous segments were considered as signs of ischemia. Significant CHD was defined as &gt;50% stenosis in a major epicardial artery on coronary angiography (CAG). Results: Among the 68 non-diabetic subjects and the 59 diabetics, 58 (85.3%) and 45 (76.3%) were found to have significant CHD on CAG, respectively. There were no significant differences as regards to age, sex and other major risk factors between diabetics and non-diabetics. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) in the total of 127 patients were 92%, 63%, 91%, 65% and 87%, respectively. These diagnostic parameters in non-diabetic vs. diabetic subjects were 93% vs. 91% (p= NS ), 90% vs. 43% (p&lt;0.01), 98% vs. 84% (p&lt;0.05) and 69% vs. 60% (p= NS ). Conclusions: Stress contrast echocardiography is an exceptionally reliable technique for CHD diagnosis. However, our findings suggest that in diabetic patients it appears to exhibit inferior specificity and PPV compared to non-diabetics. A possible explanation could be that microcirculation abnormalities, which are common in diabetes, may cause appearance of signs of ischemia (wall-motion abnormalities and/or perfusion defects) on SCE, without presence of angiographically significant CHD.
Detergent Enzymes and Occupational Safety
Authors: H. Zachariae, J. Høegh‐Thomsen, O. Witmeur, L. Wide
Journal: Allergy (1981)

During a 10-year survey of 667 workers producing the detergent enzyme Esperase, derived from an alkolophilic strain of Bacillus licheniformis, 31 were found to have been sensitized. All but one were at the same time sensitized to subtilisins, with which they also had been working. No distinction could be made between symptoms attributed to Esperase and symptoms attributed to enzymes derived from Bacillus subtilis (licheniformis) or other enzymes. Symptoms, when present, were mainly from the lower respiratory tract. Nine sensitized workers were symptom-free. Sensitization was by IgE antibodies and detected by the RAST test. Twenty-one sensitized workers were transferred for precautionary measures or left the company. All 26 sensitized workers, whom it was possible to follow and reinvestigate, were no longer RAST-positive. Ten workers remained in their jobs. No signs of deteriorating lung function or permanent lung damage were found. The study indicated that, when strictly enforced, recommended operating procedures for workers handling hitherto well-known detergent enzymes are sufficient for dealing with Esperase. The data suggest there is no significant risk of consumer sensitization.
Still Life With Fish, Vegetables, Gougères, Pots, and Cruets on a Table
Authors: M. Therese Southgate
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 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
Ivy in Flower
Authors: M. Therese Southgate
Journal: JAMA (2001)

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
Effects of systemic β-blocker therapy on the efficacy and safety of topical brimonidine and timolol11None of the clinical investigators or authors have a proprietary interest in the products discussed in this manuscript; Pamela Barnett, Amy Batoosingh, Kuankuan Chen, Robert David, MD, Marsha Harrold, and Amanda VanDenburgh are employees of Allergan, Inc.
Authors: Joel S Schuman
Journal: Ophthalmology (2000)
Handbook of Stress, Medicine and Health, by Ed Cary L Cooper
Authors: J. Herbert
Journal: BMJ (1997)

Ed Cary L Cooper CRC Press, £69, pp 388 ISBN 0 849 32908 6

Medicine has yet to decide its role in understanding and treating stress related disorders. There is a huge and increasing public interest in the part played by stress in illness, and a firm general belief that this role is a considerable one. Medical science–preoccupied with such contemporary excitements as molecular biology, transplants, and imaging technology–seems reluctant to listen to the clamour at its door.

Only psychiatry has accepted–not always unanimously–that stress can be important in the genesis of illness, and that understanding more about stress could open new avenues of treatment. Some serious proselytising is …
Cardiovascular Effects of Ephedra
Authors: Jose Ness
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 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
Evaluation of bone marrow reticulin in patients with chronic immune thrombocytopenia treated with eltrombopag: Data from the EXTEND study
Authors: Russell K. Brynes, Attilio Orazi, Dickens Theodore, Paul Burgess, Christine K. Bailey, Maung M. Thein, Kalpana K. Bakshi
Journal: American Journal of Hematology (2015)

Thrombopoietin receptor agonists, which raise platelet counts in patients with chronic immune thrombocytopenia, may be associated with increases in bone marrow (BM) reticulin. Patients with chronic immune thrombocytopenia participating in the Eltrombopag Extended Dosing (EXTEND) study underwent BM biopsies to identify clinically relevant BM fibrosis-related increases. Specimens were centrally reviewed by 2 hematopathologists. Two hundred thirty-two biopsy specimens were collected from 117 patients treated for ≤5.5 years. Moderate to marked reticulin fibrosis was found in 2 patients. After withdrawing from the study, the biopsy of 1 patient reverted to normal. There were no other pathologic changes identified among on-treatment specimens, and no pattern of abnormal reticulin deposition associated with eltrombopag treatment was evident.
Incidence of hospital admission does not equal incidence of disease
Authors: L. H Pobereskin
Journal: BMJ (2000)

Fallout from the Shipman case Deaths should be investigated more plainly and effectivelyEditor-O'Neill's editorial and the news article by Dyer, which both arose from the Shipman case, raise several points that merit further consideration. 1 2 The fact that a central registry of doctors' prescribing habits is geared to financial rather than good practice principles perhaps reflects the current fiscal climate.Concern about death certification and coroners dates back to the Brodrick committee. 3 I wonder what was entered on the death certificates of Shipman's patients, how carefully the certificates were scrutinised by the registrar of births, deaths, and marriages, and what was the degree of training and expertise of those scrutinising them.Australian experience mirrors that of the United Kingdom, with inaccuracies in death certificates.Surely, however, characterising the immediate cause of death of valued citizens, irrespective of their age or sex, can never be meddlesome.Inaccuracy in documenting any aspect of medical practice should not be readily accepted.
Abstract 11582: Catheter Ablation of Supraventricular Tachycardia in Patients With Total Cavopulmonary Connection
Authors: Keiko Toyohara, Tomomi Nishimura, Morio Shoda, Toshio Nakanishi
Journal: Circulation (2014)

Introduction: Management of arrhythmias after the Fontan operation is difficult. Total cavopulmonary connection (TCPC), rather than atriopulmonary connection, is considered the optimal method to minimize the risk of arrhythmias, although they are sometimes still observed after TCPC. Catheter ablation (CA) for supraventricular tachycardia (SVT) is extremely difficult after TCPC because the systemic venous route is excluded from the atria. The purpose of this study was to evaluate the efficacy of CA in treating SVT after TCPC. Results: CA was attempted after TCPC in 14 patients aged 8-37 years (median: 23 years). TCPC was performed using the lateral tunnel approach in 5 patients, the intra-atrial conduit procedure in 2, and the extracardiac polytetrafluoroethylene conduit procedure in 7. During CA, the atrium was approached either by a transseptal puncture (12 patients), a fenestration in the patch (1 patient), or suture leakage (1 patient). Transseptal puncture was performed using a conventional Brockenbrough needle in all 12 patients. There were no clinically significant complications and only one unsuccessful puncture. SVT included atrial flutter in 4 patients, atrial tachycardia in 7, atrioventricular reentrant tachycardia (AVRT) via the accessory pathway in 1, and AVRT involving twin atrioventricular nodes in 2. Acute treatment of SVT with CA was achieved in 10 patients (71%), but tachycardia recurred in 3 during follow-up. Deterioration of cyanosis was not observed after transseptal puncture, and closure of the puncture site was confirmed in all 12 patients. Overall, SVT was successfully managed using CA in 7 out of 14 patients (50%), and with medication in the remaining patients. Conclusions: SVT may arise after the TCPC procedure. Puncture of the extracardiac conduit is feasible, and CA can be an effective treatment option for refractory SVT after TCPC.
Prediction of challenge test results by flour‐specific IgE and skin prick test in symptomatic bakers
Authors: V. Van Kampen, S. Rabstein, I. Sander, R. Merget, T. Brüning, H. C. Broding, C. Keller, H. Müsken, A. Overlack, G. Schultze‐Werninghaus, J. Walusiak, M. Raulf‐Heimsoth
Journal: Allergy (2008)

Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker's asthma is based on inhalation challenge tests with flours.To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker's asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing.Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard.Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74-100% (74-100%) for wheat and 82-100% (91-100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour.High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers.