tbuckley/cabot-search huggingface dataset:
Modulation of Glucocorticoid Resistance in Pediatric T-cell Acute Lymphoblastic Leukemia by Increasing BIM Expression with the PI3K/mTOR Inhibitor BEZ235
Authors: Connor P. Hall, C. Patrick Reynolds, Min H. Kang
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The aim of our study is to evaluate the preclinical therapeutic activity and mechanism of action of BEZ235, a dual PI3K/mTOR inhibitor, in combination with dexamethasone in acute lymphoblastic leukemia (ALL). Experimental Design: The cytotoxic effects of BEZ235 and dexamethasone as single agents and in combination were assessed in a panel of ALL cell lines and xenograft models. The underlying mechanism of BEZ235 and dexamethasone was evaluated using immunoblotting, TaqMan RT-PCR, siRNA, immunohistochemistry, and immunoprecipitation. Results: Inhibition of the PI3K/AKT/mTOR pathway with the dual PI3K/mTOR inhibitor BEZ235 enhanced dexamethasone-induced anti-leukemic activity in in vitro (continuous cell lines and primary ALL cultures) and systemic in vivo models of T-ALL (including a patient-derived xenograft). Through inhibition of AKT1, BEZ235 was able to alleviate AKT1-mediated suppression of dexamethasone-induced apoptotic pathways leading to increased expression of the proapoptotic BCL-2 protein BIM. Downregulation of MCL-1 by BEZ235 further contributed to the modulation of dexamethasone resistance by increasing the amount of BIM available to induce apoptosis, especially in PTEN-null T-ALL where inhibition of AKT only partially overcame AKT-induced BIM suppression. Conclusions: Our data support the further investigation of agents targeting the PI3K/mTOR pathway to modulate glucocorticoid resistance in T-ALL. Clin Cancer Res; 22(3); 621–32. ©2015 AACR.
High seroprevalence of Pneumocystis infection in Spanish children
Authors: N. Respaldiza, F.J. Medrano, A.C. Medrano, J.M. Varela, C. de la Horra, M. Montes-Cano, S. Ferrer, I. Wichmann, D. Gargallo-Viola, E.J. Calderon
Journal: Clinical Microbiology and Infection (2004)
In vivo repopulating ability of genetically-corrected BM cells from Fanconi’s aneamia A patients
Authors: Odile Y. Cohen-Haguenauer, Christian Auclair, Michel Marty
Journal: Molecular Therapy (2004)

Background: Fanconi Aneamia is a rare genomic instability inherited syndrome. Allo-BMT for life-threatening aplastic aneamia is associated to acute toxicity and secondary tumours. Gene therapy is an attractive alternative while obstacles need to be overcome: (i) the scarcity of BM-stem cells; (ii) their flimsiness (iii) gene transfer technical limitations.
On the Interaction Between Tumor Viruses and Cells: A Virogenetic Concept of Tumorigenesis&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: L. A. Zilber
Journal: JNCI Journal of the National Cancer Institute (1961)

This paper presents a virogenetic concept of tumor origin. A virus induces a hereditary transformation of a normal into a tumor cell, conditioned by the supplementary genetic information brought into the normal cell with the nucleic acid of the virus. Such a process cannot be considered a mutation, which is a change of the appropriate genome of the cell, but as a conversion of a normal into a tumor cell which involves incorporation of a genetic substance carrying additional genetic information. The reproduction of the cell with transformed heredity leads to the formation of a tumor, and as an entity the virus will take no part in this process, though it may still exist in the mature form in some tumors. Certain alterations of antigenic structure occur in tumor cells, and they cease then to submit to the growth regulation systems of the organism. The data presented show that some tumors induced by chemical or physical factors are conditioned by latent viruses; therefore the above concept may have a general significance.
<i>In vitro</i>diagnostic assays are effective during the acute phase of delayed-type drug hypersensitivity reactions
Authors: M.E. Polak, G. Belgi, C. McGuire, C. Pickard, E. Healy, P.S. Friedmann, M.R. Ardern-Jones
Journal: British Journal of Dermatology (2012)

Previous reports have suggested that drug-specific lymphocyte proliferation assays (LPA) can be used retrospectively to confirm the culprit drug following delayed-type drug hypersensitivity reactions (DHR). However, only limited evidence supports their use in aiding acute clinical management. The aim of this study was to compare the LPA against combination cytokine assays for potential use in the acute setting.A total of 43 patients with DHR (19 during the acute reaction, 20 after recovery, four during acute and after recovery) and 14 control subjects without DHR were investigated using ex vivo analysis of drug-specific proliferation, and interferon (IFN)-γ and interleukin (IL)-4 production.Healthy controls showed negative drug-specific proliferation and cytokine release in contrast to individuals with a known sensitivity (P < 0·0001). The assays demonstrated a test specificity of 95% (LPA), 83% (IFN-γ) and 92% (IL-4). The sensitivity of combined measurement of drug-specific IFN-γ and IL-4 cytokines during acute DHR was better than LPA (82% vs. 50%), but all assays were less sensitive during the recovery phase. The correlation between LPA and IFN-γ assays was strong (r = 0·7, P < 0·0001), whereas the IL-4 assay did not correlate as well with either of these assays. In contrast to LPA, drug enzyme-linked immunosorbent spot assays showed positive responses in patients concurrently taking immunosuppressive medication.In vitro assays of drug-specific IFN-γ and IL-4 production offer potential for use as rapid diagnostic tests. Cytokine detection offers distinct advantages over the LPA, including a shorter assay time, a greater sensitivity and effectiveness in testing immunosuppressed patients.
ABC of diseases of liver, pancreas, and biliary system: Chronic viral hepatitis
Authors: S D Ryder
Journal: BMJ (2001)

<h3>ABSTRACT</h3> The Covid19 pandemic caused by SARS-CoV-2 has created panic around most of the nations. Statistical and epidemiological data from its predecessor SARS-CoV-1 imply temperature sensitivity of the virus. However, we still lack molecular level understanding of the same. Spike protein is the outermost structural protein of the virus which interacts with the human receptor ACE2 and enters the respiratory system. It is also one of largest proteins which have primary exposure to external environmental conditions. In this study, we performed an all atom molecular dynamics simulation to study the effect of temperature on the structure of the Spike protein. After 200ns of simulation at different temperatures, we came across some interesting phenomena exhibited by the protein. We found that the receptor binding motif of the virus is sensitive to the surrounding temperature and behaves differently at altered temperatures. Bioinformatics and structural studies hinted that the N-terminal Domain of the Spike protein is capable of binding to receptors and should not be overlooked. We also observed that at higher temperatures, the structure of the Spike protein is in a more confined conformation. The study would not only prove very beneficial for understanding the fundamental nature of the virus, but will also support in the development of vaccines and therapeutics.
Geographical Differences In Transfusion and Iron Chelation Practices In 1558 Patients with Transfusion-Dependent Anemias
Authors: Vip Viprakasit, Norbert Gattermann, Jong Wook Lee, John B. Porter, Ali Taher, Dany Habr, Bernard Roubert, Gabor Domokos, Maria Domenica Cappellini
Journal: Blood (2010)
A NEW TYPE OF GRADUATE COURSE IN INTERNAL MEDICINE
Authors: N. L. Crone, J. H. Means
Journal: Annals of Internal Medicine (1941)

Article1 June 1941A NEW TYPE OF GRADUATE COURSE IN INTERNAL MEDICINEN. L. CRONE, M.D., J. H. MEANS, M.D., F.A.C.P.N. L. CRONE, M.D.Search for more papers by this author, J. H. MEANS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-12-2292 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe development in recent years of a steadily mounting demand for graduate training in the specialties, including that of internal medicine, of a sustained and practical sort, quite different from that provided by the usual "refresher" course, has occasioned a search for new types of curriculum. Hospital residencies, to be sure, may provide such training, but with the pressure generated by the various specialty boards the opportunities which residencies provide are inadequate.To meet the demand in a new way, in the field of internal medicine, the course which we are about to describe was put into operation in the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*From the Medical Clinic of the Massachusetts General Hospital and the Harvard Medical School Courses for Graduates.†The money received in fees is used to pay salaries to those instructors devoting a considerable amount of time to the course, chiefly the tutor in general charge. The payment in service may be looked upon as payment to the clinic for overhead and for a considerable amount of instruction given by many of its staff, without remuneration, as part of their regular routine. That is to say, the graduate student helps the clinic, and in turn the clinic helps the graduate student. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1941Volume 14, Issue 12Page: 2292-2295KeywordsGraduate medical educationHospital medicineResidency ePublished: 1 December 2008 Issue Published: 1 June 1941 PDF downloadLoading ...
Gene Fusion Found in Prostate Cancer
Authors: Tracy Hampton
Journal: JAMA (2005)

Back the Same is an abstract female figure with hair fashioned from 2400 bobby pins. The work’s title recalls women’s many conversations about hair loss. In Dear Diary, a head swathed in snippets of Mary’s extensive treatmentrelated paperwork rests on a pillow. Mary made the pillowcase from a skirt she could not fasten after developing abdominal bloating, a characteristic but often overlooked symptom of ovarian cancer. She embroidered her treatment dates on the pillowcase. A 7-foot-square photo montage overlooks the exhibit, featuring 25 digitally enhanced candid snapshots of Mary. The first photo shows Mary before her diagnosis, her hair wind-tossed. In most of those taken during treatment, she wears a colorful hat, a scarf, or a wig, along with a pearl necklace and, almost always, a smile. In three, she is bald. Finally, there is Mary in remission, her hair growing back, shorter and grayer; she wears dangling earrings with stars. This work’s title: Survivor. Funding for the show comes from the Massachusetts General Hospital Cancer Center; the National Ovarian Cancer Coalition, based in Boca Raton, Fla; and other donors. The exhibit has made nine previous stops around the country and will open in Spartanburg, SC, in May 2006. For information on the Washington exhibit, see http://www .nmhm.washingtondc.museum. For images and John Magnan’s comments on the works, see http://www .bodyimage-bodyessence.com.
Cluster randomised trials: time for improvement
Authors: M. K Campbell, J. M Grimshaw
Journal: BMJ (1998)

Cluster randomised trials, where groups of patients rather than individuals are randomised, are increasingly being used in health services research. Randomisation by individual is inappropriate for evaluating some interventions, such as organisational changes, where it may not be feasible to randomise at the patient level. In such cases cluster randomisation at the level of the health professional or organisation is necessary. Such randomisation can also minimise the potential for contamination between treatments when trial patients are managed within the same setting.

The main consequence of adopting a cluster design is that the outcome for each patient can no longer be assumed to be independent of that for any other patient (which is the case in an individually randomised trial). Patients within any one cluster are more likely to have similar outcomes. For example, the management of patients within a single general practice is more likely to be consistent …
<i>Trouville, The Jetties, High Tide</i>
Authors: M. Therese Southgate
Journal: JAMA (2003)

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 Journals 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 2024 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
Abstract 5144: Extended-Release Niacin Reduces LDL-C Particle Number Even In The Absence Of Changes In Total LDL-C Levels
Authors: Haseeb Jafri, Jeffrey T Kuvin, Alawi A Alsheikh-Ali, Paula Mooney, Carey D Kimmelstiel, Richard H Karas
Journal: Circulation (2008)

Introduction: The importance of the number of circulating low-density lipoprotein cholesterol (LDL-C) particles, in addition to the total level of LDL-C is increasingly recognized. The effects of Extended Release Niacin (ERN) on LDL-C particle number have not been studied. The primary objective of this study was to evaluate ERN’s effects on LDL-C particle number. ERN’s effect on high-density lipoprotein cholesterol (HDL-C) particle number was a secondary objective. Hypothesis : In patients with stable coronary artery disease (CAD) and LDL-C at goal, the addition of ERN will favorably alter LDL-C particle number. Methods: 60 patients with stable CAD and well-controlled LDL-C levels were randomly assigned to 3 months of ERN (1g/d) or placebo in addition to their baseline medications. Particle number was analyzed by proton nuclear magnetic resonance spectroscopy at baseline and after 3 months. Results: Baseline and follow up lipid values are shown in Table . Compared to baseline, while ERN had no significant effect on total LDL-C levels, it significantly decreased the mean number of medium and small very small LDL-C particles (p=0.005). The percent change in each of these particle numbers was significantly greater in the ERN group compared to placebo as well (p&lt;0.05 for each) ERN therapy raised HDL-C levels and also significantly shifted from small to large HDL-C particles (p&lt;0.001). There were no significant changes in lipid values or particle numbers in the placebo-treated patients ( Table ). Conclusion: In patients with stable CAD and well-controlled LDL-C levels, ERN significantly reduced the number of circulating particles of the more atherogenic subtypes of LDL-C, despite having no effect on total LDL-C levels. ERN also favorably altered particle numbers of HDL-C. These findings suggest that ERN-induced alterations in particle number may contribute to its anti-atherosclerotic effects, and that these effects may not be evident from the standard lipid profile.
Soluble receptor of advanced glycation end products levels are related to ischaemic aetiology and extent of coronary disease in chronic heart failure patients, independent of advanced glycation end products levels
Authors: Sergio Raposeiras‐Roubín, Bruno K. Rodiño‐Janeiro, Lilian Grigorian‐Shamagian, María Moure‐González, Ana Seoane‐Blanco, Alfonso Varela‐Román, Ezequiel Alvarez, José R. González‐Juanatey
Journal: European Journal of Heart Failure (2010)
Books CDs: QBase: Anaesthesia: 1-3
Authors: I. Barker
Journal: BMJ (1999)

QBase: Anaesthesia: 1 E Hammond Greenwich Medical Media, £19.50, pp 160 ISBN 1 900151 758 QBase: Anaesthesia: 2 E Hammond, Andrew McIndoe Greenwich Medical Media, £19.50, pp 208 ISBN 1 900151 324 QBase: Anaesthesia: 3 E Hammond, Andrew McIndoe Greenwich Medical Media, £22.50, pp 208 ISBN 1 900151 588 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> (books ![Graphic][4]</img>![Graphic][5]</img>![Graphic][6]</img>, CDs ![Graphic][7]</img>![Graphic][8]</img>) Candidates have different techniques for answering multiple choice exams. Many simply tick the answers they believe to be correct and then leave the room, but there are other, more complex, patterns of behaviour: the gambler, “I'm not sure about this answer, but the chances are that it's correct so I'll tick it”; the bookmaker, “If I answer 75% of the questions correctly then I'll pass the exam no matter what the results of the rest”; the compulsive ticker, “I can't bear to see both boxes left blank without my pencil mark … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif [5]: /embed/inline-graphic-5.gif [6]: /embed/inline-graphic-6.gif [7]: /embed/inline-graphic-7.gif [8]: /embed/inline-graphic-8.gif
ET-03 * CAVITATION-BASED THIRD VENTRICULOSTOMY USING MRI-GUIDED FOCUSED ULTRASOUND
Authors: R. Alkins, Y. Huang, K. Hynynen
Journal: Neuro-Oncology (2014)

Transcranial focused ultrasound is increasingly being investigated as a minimally invasive treatment for a range of intracranial pathologies. At higher peak rarefaction pressures than those used for thermal ablation, focused ultrasound can initiate inertial cavitation and create holes in the brain by fractionation of the tissue elements. We investigated the technical feasibility of using MRI-guided focused ultrasound to perform a third ventriculostomy as a possible noninvasive alternative to endoscopic third ventriculostomy for hydrocephalus. A craniectomy was performed in male pigs weighing 13-19 kg to expose the supratentorial brain, leaving the dura mater intact. Seven pigs were treated through the craniectomy, while 2 pigs were treated through ex vivo human skulls placed in the beam path. Registration and targeting was done using T2-weighted MRI sequences. For transcranial treatments a CT scan was used to correct the beam from aberrations due to the skull and maintain a small, high-intensity focus. Sonications were performed at both 650 kHz and 230 kHz at a range of intensities, and the in situ pressures were estimated both from simulations and experimental data to establish a threshold for tissue fractionation in the brain. In craniectomized animals at 650 kHz, a peak pressure 3 22.7 MPa for 1 second was needed to reliably create a ventriculostomy. Transcranially at this frequency the ExAblate 4000 was unable to generate the required intensity to fractionate tissue, although cavitation was initiated. At 230 kHz, ventriculostomy was successful through the skull with a peak pressure of 8.8 MPa. This is the first study to suggest that it is possible to perform a completely noninvasive third ventriculostomy using ultrasound. This may pave the way for future studies and eventually provide an alternative, non-invasive means for the creation of CSF communications in the brain, including perforation of the septum pellucidum or intraventricular membranes.
Abstract 1639: Development of novel thiobarbituric acid derivatives as potential cancer therapeutics
Authors: Srinivasa R. Ramisetti, Sang Y. Lee, Manoj K. Pandey, Shantu G. Amin, Arun K. Sharma
Journal: Cancer Research (2014)

Abstract Chemotherapy drugs for the treatment of cancer are generally directed to inhibit the reproduction of malignant cells and killing cells, thereby preventing tumor growth or reducing tumor size. Many of these drugs develop resistance to tumor cells by different mechanisms. Therefore a significant clinical need exists for the development of additional chemotherapeutic agents that are toxic to a wide range of tumor cells, in particular tumors that are resistant to current treatments such as radiotherapy and chemotherapy. From recent past, it has been known that barbituric acid derivatives exhibit different biological activities such as anti-depressant, anti-convulsant, anti-viral and anti-cancer activities. Among them some thiobarbituric acid derivatives, such as merocyanine and merbarone have been proposed as possible modulators of apoptosis in several cancer cells including glioblastoma multiforme (GBM), lung, melanoma, leukemia, breast cancer, prostate cancer, and cervical cancer; albeit not particularly for cancers that are resistant to current therapy. We designed and synthesized novel thio- and seleno- barbituric derivatives by varying the substituents at N1, N3 (ethyl, methyl, allyl, and phenyl) and C5 tethered with dienyl and trienyl moieties attached with different substituents like phenyl, 2-furanyl, 2-thiophenyl, 1-naphthyl &amp; 3-pyridyl. These compounds were tested against both chemotherapy sensitive and resistant, melanoma (UACC903 and CHL-1), GBM (U87-MG, T98G, and CCF-STTG1) , and lung cancer (A549, H460, H520and H69) cells. Most of these compounds reduced cell viability in a dose and time dependent manner. Among all the compounds ASR-198, ASR-199, ASR-243 and ASR-244 were most cytotoxic to both chemotherapy resistant and sensitive cells. In addition, these compounds triggered a dose dependent induction of apoptosis by activation of caspase-3 and PARP cleavage in melanoma cells. Overall compound ASR-198, having a 2-thiophen-dienyl substitution and C-5 position, emerged as the most efficacious compound in all three cancer cell lines. Interestingly its isosteric selenium analogs were relatively less cytotoxic. In summary, this structure-activity relationship study clearly indicates that more efficacious compounds, compared to existing thiobarbituric analogs, can be developed based on barbituric acid scaffold, by rational modifications of the chemo type compounds. Detailed results of these investigations will be presented. Citation Format: Srinivasa R. Ramisetti, Sang Y. Lee, Manoj K. Pandey, Shantu G. Amin, Arun K. Sharma. Development of novel thiobarbituric acid derivatives as potential cancer therapeutics. [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 1639. doi:10.1158/1538-7445.AM2014-1639
CD40 activation in vivo overcomes peptide-induced peripheral cytotoxic T-lymphocyte tolerance and augments anti-tumor vaccine efficacy
Authors: Linda Diehl, Annemieke Th. den Boer, Stephen P. Schoenberger, Ellen I.H. van der Voort, Ton N.M. Schumacher, Cornelis J.M. Melief, Rienk Offringa, Rene E. M. Toes
Journal: Nature Medicine (1999)