tbuckley/cabot-search huggingface dataset:
Immune-Regulatory Molecule CD69 Controls Peritoneal Fibrosis
Authors: Georgios Liappas, Guadalupe Tirma González-Mateo, Raquel Sánchez-Díaz, Juan José Lazcano, Sandra Lasarte, Adela Matesanz-Marín, Rafal Zur, Evelina Ferrantelli, Laura García Ramírez, Abelardo Aguilera, Elena Fernández-Ruiz, Robert H.J. Beelen, Rafael Selgas, Francisco Sánchez-Madrid, Pilar Martín, Manuel López-Cabrera
Journal: Journal of the American Society of Nephrology (2016)

Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69−/− mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody–mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69−/− mice. Finally, IL-17 blockade in cd69−/− mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from c d69 −/− and Rag2 −/− γ c −/− mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in c d69 −/− mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation.
Risk factors for hospital utilization in chronic dialysis patients. Southeastern Kidney Council (Network 6).
Authors: M V Rocco, J M Soucie, D M Reboussin, W M McClellan
Journal: Journal of the American Society of Nephrology (1996)

It is not known if the risk factors for hospital utilization are similar to the risk factors for mortality in chronic dialysis patients. The risk factors associated with hospital days per year of patient risk were identified in a subset of patients in Network 6 (the states of North Carolina, South Carolina, and Georgia) who began dialysis in 1989. The demographic characteristics of this cohort of 1572 patients included a mean (+/- SD) age of 57.4 +/- 15.0 yr; 63.7% of the patients were African American, 52.4% were female, and 33.0% had diabetes mellitus as the primary cause of ESRD. The median number of hospital days per year of patient risk was 8.8, with 25th and 75th quartiles of 3.9 and 20.1, respectively. By using multiple regression analysis, the strongest predictors of the number of hospital days per year of patient risk included low serum albumin level (P = 0.0001), decreased activity level (P = 0.0006), diabetes mellitus as the primary cause of ESRD (P = 0.002), peripheral vascular disease (P = 0.004), white race (P = 0.01), increasing age (P = 0.03), the absence of hypertension (P = 0.03), and the presence of angina (P = 0.03), smoking (P = 0.03), and congestive heart failure (P = 0.045). These risk factors are similar to those reported for an increased risk of mortality in dialysis patients and some of them, such as smoking, are modifiable and may be amenable to interventional strategies.
Assessing Temporal and Spatial Patterns of Observed and Predicted Ozone in Multiple Urban Areas
Authors: Heather Simon, Benjamin Wells, Kirk R. Baker, Bryan Hubbell
Journal: Environmental Health Perspectives (2016)

Ambient monitoring data show spatial gradients in ozone (O3) across urban areas. Nitrogen oxide (NOx) emissions reductions will likely alter these gradients. Epidemiological studies often use exposure surrogates that may not fully account for the impacts of spatially and temporally changing concentrations on population exposure.We examined the impact of large NOx decreases on spatial and temporal O3 patterns and the implications on exposure.We used a photochemical model to estimate O3 response to large NOx reductions. We derived time series of 2006-2008 O3 concentrations consistent with 50% and 75% NOx emissions reduction scenarios in three urban areas (Atlanta, Philadelphia, and Chicago) at each monitor location and spatially interpolated O3 to census-tract centroids.We predicted that low O3 concentrations would increase and high O3 concentrations would decrease in response to NOx reductions within an urban area. O3 increases occurred across larger areas for the seasonal mean metric than for the regulatory metric (annual 4th highest daily 8-hr maximum) and were located only in urban core areas. O3 always decreased outside the urban core (e.g., at locations of maximum local ozone concentration) for both metrics and decreased within the urban core in some instances. NOx reductions led to more uniform spatial gradients and diurnal and seasonal patterns and caused seasonal peaks in midrange O3 concentrations to shift from midsummer to earlier in the year.These changes have implications for how O3 exposure may change in response to NOx reductions and are informative for the design of future epidemiology studies and risk assessments.Simon H, Wells B, Baker KR, Hubbell B. 2016. Assessing temporal and spatial patterns of observed and predicted ozone in multiple urban areas. Environ Health Perspect 124:1443-1452; http://dx.doi.org/10.1289/EHP190.
Noninvasive Ventilation and Outcomes Among Immunocompromised Patients
Authors: Jean-Pierre Frat, Rémi Coudroy, Arnaud W. Thille
Journal: JAMA (2016)

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
Boxed Warning for Most Opioids
Authors: Rebecca Voelker
Journal: JAMA (2016)

In a related step to tackle opioid abuse, the FDA recently announced labeling changes, including a boxed warning, for immediate-release (IR) opioid pain medications. The changes will affect more than 200 opioid-containing products, FDA officials said during a media briefing.

“I can’t stress enough how critical it is for prescribers to have the most current information about the potential risks these products pose to both patients and nonpatients,” FDA Commissioner Robert Califf, MD, said during the briefing (http://1.usa.gov/1MF96rY).
CSF somatostatin in patients with Alzheimer's disease, older depressed patients, and age-matched control subjects
Authors: T Sunderland, D R Rubinow, P N Tariot, R M Cohen, P A Newhouse, A M Mellow, E A Mueller, D L Murphy
Journal: American Journal of Psychiatry (1987)

Somatostatin-like immunoreactivity was measured in the CSF of 12 patients with Alzheimer's disease, 15 age-matched control subjects, and 20 older depressed subjects. Patients with dementia or depression were found to have lower CSF somatostatin concentrations than control subjects despite markedly different clinical presentations. Severity of depression was clearly different in all three groups but showed no significant correlation with CSF concentration of somatostatin. There was a significant positive correlation between CSF somatostatin-like immunoreactivity and cognitive functioning in all 47 subjects, but this association was not statistically significant within individual diagnostic groups. These data raise interesting questions about possible biological links between Alzheimer's disease and depression in older patients.
Utilidad de la USE-PAAF en el diagnóstico del Cáncer de Páncreas. Experiencia en nuestro centro
Authors: A Jiménez-García Victoria, R Romero-Castro, F Argüelles-Arias, M Rodríguez-Téllez, J Romero-Vázquez, F Pellicer-Bautista, A Nogales-Muñoz, A Caunedo-Álvarez, M Romero-Gómez, JM Herrerias
Journal: Endoscopy (2015)

Introducción: La Ultrasonografía Endoscópica con Punción-Aspiración con Aguja Fina (USE-PAAF) juega un papel importante en el diagnóstico del cáncer de páncreas (CP), con una sensibilidad (S) del 80 – 95% y una especificidad del 75 – 100%.
Postoperative Radiotherapy in Resected Ypn2 Stage Iii-N2 Non-Small Cell Lung Cancer: Can Modern Conformal Radiotherapy Compensate for the Poor Outcome?
Authors: C. Billiet, Z. Gouw, G. Defraene, H. Decaluwe, S. Peeters, J.F. Vansteenkiste, P. De Leyn, C. Dooms, D. De Ruysscher
Journal: Annals of Oncology (2014)
前処置強度を弱めた造血幹細胞移植(RIST)後の治療関連毒性(RRT):Bearmanの基準とNCI‐CTC2.0版の比較
Authors: Sakiyama M, Kami M, Hori A, Imataki O, Kojima R, Kim Sw, Makimoto A, Tanosaki R, Mineishi S, Takaue Y
Journal: Blood (2002)
ASH1L Links Histone H3 Lysine 36 Dimethylation to MLL Leukemia
Authors: Li Zhu, Qin Li, Stephen H.K. Wong, Min Huang, Brianna J. Klein, Jinfeng Shen, Larissa Ikenouye, Masayuki Onishi, Dominik Schneidawind, Corina Buechele, Loren Hansen, Jesús Duque-Afonso, Fangfang Zhu, Gloria Mas Martin, Or Gozani, Ravindra Majeti, Tatiana G. Kutateladze, Michael L. Cleary
Journal: Cancer Discovery (2016)

Numerous studies in multiple systems support that histone H3 lysine 36 dimethylation (H3K36me2) is associated with transcriptional activation; however, the underlying mechanisms are not well defined. Here, we show that the H3K36me2 chromatin mark written by the ASH1L histone methyltransferase is preferentially bound in vivo by LEDGF, a mixed-lineage leukemia (MLL)-associated protein that colocalizes with MLL, ASH1L, and H3K36me2 on chromatin genome wide. Furthermore, ASH1L facilitates recruitment of LEDGF and wild-type MLL proteins to chromatin at key leukemia target genes and is a crucial regulator of MLL-dependent transcription and leukemic transformation. Conversely, KDM2A, an H3K36me2 demethylase and Polycomb group silencing protein, antagonizes MLL-associated leukemogenesis. Our studies are the first to provide a basic mechanistic insight into epigenetic interactions wherein placement, interpretation, and removal of H3K36me2 contribute to the regulation of gene expression and MLL leukemia, and suggest ASH1L as a novel target for therapeutic intervention.Epigenetic regulators play vital roles in cancer pathogenesis and represent a new frontier in therapeutic targeting. Our studies provide basic mechanistic insight into the role of H3K36me2 in transcription activation and MLL leukemia pathogenesis and implicate ASH1L histone methyltransferase as a promising target for novel molecular therapy. Cancer Discov; 6(7); 770-83. ©2016 AACR.See related commentary by Balbach and Orkin, p. 700This article is highlighted in the In This Issue feature, p. 681.
Day-and-Night Closed-Loop Glucose Control in Patients With Type 1 Diabetes Under Free-Living Conditions: Results of a Single-Arm 1-Month Experience Compared With a Previously Reported Feasibility Study of Evening and Night at Home
Authors: Eric Renard, Anne Farret, Jort Kropff, Daniela Bruttomesso, Mirko Messori, Jerome Place, Roberto Visentin, Roberta Calore, Chiara Toffanin, Federico Di Palma, Giordano Lanzola, Paolo Magni, Federico Boscari, Silvia Galasso, Angelo Avogaro, Patrick Keith-Hynes, Boris Kovatchev, Simone Del Favero, Claudio Cobelli, Lalo Magni, J. Hans DeVries
Journal: Diabetes Care (2016)

OBJECTIVE After testing of a wearable artificial pancreas (AP) during evening and night (E/N-AP) under free-living conditions in patients with type 1 diabetes (T1D), we investigated AP during day and night (D/N-AP) for 1 month. RESEARCH DESIGN AND METHODS Twenty adult patients with T1D who completed a previous randomized crossover study comparing 2-month E/N-AP versus 2-month sensor augmented pump (SAP) volunteered for 1-month D/N-AP nonrandomized extension. AP was executed by a model predictive control algorithm run by a modified smartphone wirelessly connected to a continuous glucose monitor (CGM) and insulin pump. CGM data were analyzed by intention-to-treat with percentage time-in-target (3.9–10 mmol/L) over 24 h as the primary end point. RESULTS Time-in-target (mean ± SD, %) was similar over 24 h with D/N-AP versus E/N-AP: 64.7 ± 7.6 vs. 63.6 ± 9.9 (P = 0.79), and both were higher than with SAP: 59.7 ± 9.6 (P = 0.01 and P = 0.06, respectively). Time below 3.9 mmol/L was similarly and significantly reduced by D/N-AP and E/N-AP versus SAP (both P &amp;lt; 0.001). SD of blood glucose concentration (mmol/L) was lower with D/N-AP versus E/N-AP during whole daytime: 3.2 ± 0.6 vs. 3.4 ± 0.7 (P = 0.003), morning: 2.7 ± 0.5 vs. 3.1 ± 0.5 (P = 0.02), and afternoon: 3.3 ± 0.6 vs. 3.5 ± 0.8 (P = 0.07), and was lower with D/N-AP versus SAP over 24 h: 3.1 ± 0.5 vs. 3.3 ± 0.6 (P = 0.049). Insulin delivery (IU) over 24 h was higher with D/N-AP and SAP than with E/N-AP: 40.6 ± 15.5 and 42.3 ± 15.5 vs. 36.6 ± 11.6 (P = 0.03 and P = 0.0004, respectively). CONCLUSIONS D/N-AP and E/N-AP both achieved better glucose control than SAP under free-living conditions. Although time in the different glycemic ranges was similar between D/N-AP and E/N-AP, D/N-AP further reduces glucose variability.
Development of optimal Lu-177 labeled monoclonal antibody (7E11) constructs for radioimmunotherapy of prostate cancer
Authors: J. Tedesco, W. Goeckeler, M. Becker, K. Frank, G. Gulyas, S. A. Young
Journal: Journal of Clinical Oncology (2005)

4765 Background: Prostate-specific membrane antigen (PSMA) is highly over expressed on the surface of prostate cancer cells. Radioimmunoimaging using an anti-PSMA monoclonal antibody (7E11) coupled to Indium-111 via the bifunctional chelating agent (BFC) GYK-DTPA is currently FDA approved. In prior clinical studies evaluating therapeutic constructs of this antibody and BFC labeled with Y-90, the dose that could be safely administered was limited by toxicity secondary to loss of radionuclide from the BFC. We have investigated the use of kinetically inert cyclic BFCs (of the DOTA family) conjugated to this antibody and labeled with Lutetium-177 to produce immunoconjugates that reduce radiation doses to bone marrow thereby allowing administration of higher and potentially more efficacious doses. Methods: A number of DOTA based 7E11 immunoconjugates were generated using a variety of pH, ionic and temperature conditions. Characterization of the resultant immunoconjugates was performed using SDS-PAGE and HPSEC to assess purity and apparent molecular weight and MALDI-MS to determine ratios of BFC to antibody. Specificity and biological activity of the resultant conjugates were evaluated using an immunoaffinity binding ELISA that targets the N-terminal epitope on PSMA recognized by 7E11. Optimal radiolabeling conditions using Lu-177 have also been determined. Results: Conjugation of DOTA based BFC to 7E11 has been achieved using conditions that preserve the integrity of 7E11 and its ability to specifically bind PSMA. Molar ratios of linker to antibody ranged from 0.2 to 5.3. Purity of the immunoconjugates ranged from 96% to 98%. These conjugates have also been shown to be more stable than previous constructs resulting in lower levels of loss of radionuclide in both in vitro and in vivo studies. Conclusions: Based on these studies, a Lutetium-177 labeled radioimmunoconjugate that should allow administration of higher doses than previous constructs has been developed and is being scaled up for human clinical testing. No significant financial relationships to disclose.
Gap in lifespan of rich and poor grows for the first time in 150 years
Authors: Ingrid Torjesen
Journal: BMJ (2016)

The gap between the life expectancy of rich and poor people in England and Wales has increased for the first time in almost 150 years, a report from the Cass Business School and the International Longevity Centre-UK (ILC-UK) has found.1

Using data from the Human Mortality Database, the report’s authors measured the differences in age between the earliest 10% of adult deaths in England and Wales and the latest 5%.

They found that while …
Small-bowel pseudomelanosis
Authors: Eduardo Rodrigues-Pinto, Helder Cardoso, Rosa Coelho, Margarida Marques, Patricia Andrade, Nataly Dantas, Guilherme Macedo
Journal: Endoscopy (2015)

An 80-year-old man with a past medical history of hypertension and stage 3 chronic renal failure was referred for capsule enteroscopy because of iron deficiency anemia without overt bleeding. Previous upper gastrointestinal endoscopy and colonoscopy had revealed no significant changes. He had been on oral therapy with ferrous sulfate, in addition to candesartan cilexitil/hydrochlorothiazide.
METB-08INHIBITION OF HEXOKINASE 2 USING TUMOR GLYCOLYSIS INHIBITORS IDENTIFIED THROUGH A DRUG SCREEN INHIBITS GLIOBLASTOMA GROWTH IN VITRO AND IN VIVO
Authors: Gelareh Zadeh, Kenneth Aldape, Mira Li, Sameer Agnihotri, Kelly Burrell, Alenoush Vartanian, Amir Alamsahebpour, Shahrzad Jalali
Journal: Neuro-Oncology (2015)

METB-08. INHIBITION OF HEXOKINASE 2 USING TUMOR GLYCOLYSIS INHIBITORS IDENTIFIED THROUGH A DRUG SCREEN INHIBITS GLIOBLASTOMA GROWTH IN VITRO AND IN VIVO Gelareh Zadeh1,2, Kenneth Aldape1, Mira Li1, Sameer Agnihotri1, Kelly Burrell1, Alenoush Vartanian1, Amir Alamsahebpour1, and Shahrzad Jalali1; MacFeeters Hamilton Center for Neuro-Oncology, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada Current research in cancer has demonstrated that normal and cancer cells use glucose differently. Normal cells will use glycolysis and oxidative phosphorylation to generate ATP, whereas proliferating tumor cells have additional demands including biomass generationand harbor glycolysis rates up to 200 times higher than normal cells. To generate biomass, proliferating tumor cells preferentially use the Warburg effect or aerobic glycolysis and in the process consume less oxygen and produce large amounts of lactate. Our ongoing work has demonstrated that hexokinase 2 (HK2) but not HK1 or HK3 is a critical mediatorof the Warburg effect in glioblastomas (GB). Currently, no direct inhibitor of HK2 exists. By using a systems biology approach and a rationale drug screen we identified several azole antifungal agents as inhibitors of tumor metabolism that reduce proliferation, lactate production, glucose uptake in GB cells but not in primary normal human astrocytes or normal neural stem cells. Dynamic metabolic flux analysis with 13C-labeling experiments followed by liquid chromatography-mass spectrometry (LC-MS) demonstrated that GB cell lines and GB glioma stem cell cultures treated with several azoles reduced some pro-anabolic glycolytic intermediates. Loss of HK2inGBcells dampened theeffectof several azoles suggesting that themechanism of action is mediated in part through HK2. Furthermore, we tested several azole compounds known to cross the blood brain barrier in vivo. Clinically achievable doses of azoles as single agents increased survival in several orthotopic xenograft GB mouse models. Current studies are underway to determine the oncogenic molecular pathways inhibited by these drug compounds and whether azole treatment with the current standard of care (temozolomide and radiation) has a synergistic effect in vivo. In summary, the azole class of antifungals may represent a new way of targeting tumor metabolism in tumors dependent on aerobic glycolysis. Neuro-Oncology 17:v135–v137, 2015. doi:10.1093/neuonc/nov221.8 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.
Next-Generation NAMPT Inhibitors For ALL Identified By Sequential High-Throughput Phenotypic Chemical and Functional Genomic Screens
Authors: Michael C. Wei, Christina J. Matheny, Michael C. Bassik, Alicia J. Donnelly, Martin Kampmann, Masayuki Iwasaki, Obdulio Piloto, David E. Solow-Cordero, Donna Bouley, Rachel E. Rau, Patrick Brown, Michael T. McManus, Jonathan S. Weissman, Michael L. Cleary
Journal: Blood (2013)
A Phase II Study Of Proteasome-Inhibition For Initial Therapy Of Chronic Graft-Versus-Host Disease
Authors: Alex F. Herrera, Haesook T. Kim, Bhavjot Bindra, Edwin P. Alyea, Philippe Armand, Corey S. Cutler, Vincent T. Ho, Jerome Ritz, Bruce R. Blazar, Joseph H. Antin, Robert J. Soiffer, John Koreth
Journal: Blood (2013)
Red-blood-cell alloimmunisation in relation to antigens' exposure and their immunogenicity: a cohort study
Authors: Dorothea Evers, Rutger A Middelburg, Masja de Haas, Saurabh Zalpuri, Karen M K de Vooght, Daan van de Kerkhof, Otto Visser, Nathalie C Péquériaux, Francisca Hudig, Henk Schonewille, Jaap Jan Zwaginga, Johanna G van der Bom
Journal: The Lancet Haematology (2016)
A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth
Authors: Henk M. De Feyter, Kevin L. Behar, Jyotsna U. Rao, Kirby Madden-Hennessey, Kevan L. Ip, Fahmeed Hyder, Lester R. Drewes, Jean-François Geschwind, Robin A. de Graaf, Douglas L. Rothman
Journal: Neuro-Oncology (2016)

Background.The dependence of tumor cells, particularly those originating in the brain, on glucose is the target of the ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations.The use of ketogenic diets has been of particular interest for therapy in brain tumors, which reportedly lack the ability to oxidize ketone bodies and therefore would be starved during ketosis.Because studies assessing the tumors' ability to oxidize ketone bodies are lacking, we investigated in vivo the extent of ketone body oxidation in 2 rodent glioma models.Methods.Ketone body oxidation was studied using 13 C MR spectroscopy in combination with infusion of a 13 C-labeled ketone body (beta-hydroxybutyrate) in RG2 and 9L glioma models.The level of ketone body oxidation was compared with nontumorous cortical brain tissue.Results.The level of 13 C-beta-hydroxybutyrate oxidation in 2 rat glioma models was similar to that of contralateral brain.In addition, when glioma-bearing animals were fed a ketogenic diet, the ketone body monocarboxylate transporter was upregulated, facilitating uptake and oxidation of ketone bodies in the gliomas.Conclusions.These results demonstrate that rat gliomas can oxidize ketone bodies and indicate upregulation of ketone body transport when fed a ketogenic diet.Our findings contradict the hypothesis that brain tumors are metabolically inflexible and show the need for additional research on the use of ketogenic diets as therapy targeting brain tumor metabolism.
Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial
Authors: Gillian M Duchesne, Henry H Woo, Julie K Bassett, Steven J Bowe, Catherine D'Este, Mark Frydenberg, Madeleine King, Leo Ledwich, Andrew Loblaw, Shawn Malone, Jeremy Millar, Roger Milne, Rosemary G Smith, Nigel Spry, Martin Stockler, Rodney A Syme, Keen Hun Tai, Sandra Turner
Journal: The Lancet Oncology (2016)