tbuckley/cabot-search huggingface dataset:
Induced Ovarian and Adrenal Tumors&lt;xref ref-type="fn" rid="fn1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Katharine P. Hummel
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Induced Ovarian and Adrenal Tumors Get access Katharine P. Hummel Katharine P. Hummel Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 711–715, https://doi.org/10.1093/jnci/15.3.711 Published: 01 December 1954
Bangers and cash: multicentre survey of what doctors are driving Commentary: Report of statistical referee
Authors: F. J Cooke, D. B Richards, C. F Kellett, R. E Morse, J. Morris
Journal: BMJ (1999)

Unlike general practitioners, most hospital doctors do not use their car for work.Choice may therefore reflect individual character and aspirations.Although influenced by income and lifestyle, the ultimate decision may be determined by other less practical factors.At all price levels, some cars are more charismatic than others; the cost of this charisma is usually practicality.We have tested whether the 1960s stereotype of the dashing surgeon in a convertible sports car still exists.An extensive literature search drew a blank.
Predictors factors for asthma in patients with rhinitis
Authors: Marta Ferrer Galván, Pilar Pérez Morilla, Juan Francisco Medina Gallardo, Auxiliadora Romero Falcón, Mayra Parra Pérez, Pablo Pérez Navarro, Francisco Javier Álvarez Gutiérrez
Journal: European Respiratory Journal (2014)

Introduction   It has been found an increased risk of asthma up to 4 times higher in patients with rhinitis, especially if it is allergic rhinitis.   Objetive   We aimed to study predictive factors of asthma in patients with rhinitis.   Methodology   It has been monitored for more than 10 years a total of 639 patients diagnosed in the first revision of rhinitis and bronchial asthma (RBA), rhinitis without asthma (R) and bronchial asthma without rhinitis (BA). After more than 10 years since diagnosis, we contacted by telephone with all patients to have a follow questionnaire for symptoms of rhinitis and / or bronchial asthma. Those patients with a history of just rhinitis were cited and reviewed looking for a possible diagnosis of asthma too. We collected clinical data,presence of atopy ( total and specific IgE and prick test study), degree of current asthma control, respiratory function, inflammation study (exhaled FeNO), methacholine challenge test or mannitol if it was necessary. Statistical analysis was performed using logistic regression using the step wise method, analyzing all the parameters included in the first review.   Results   The current average age of patients was 40.3 (±13 ) years. At the initial visit 354 patients (55.4 %) had RBA, 259 (40.5 %) R and 26 (4.1 %) BA. 37.1% of patients with rhinitis suffer from asthma at the end. In the logistic regression analysis we found that the predictors factors for asthma were family history of asthma, history of childhood infection and atopy.   Conclusions   In our serie, 37 % of patients with rinhitis suffer from asthma when we follow-up over 10 years. We identified as predictors factors for asthma a family history of asthma, childhood infections and atopy .
Waiving confidentiality for the greater good
Authors: An-Wen Chan, Ross Upshur, Jerome A Singh, Davina Ghersi, François Chapuis, Douglas G Altman
Journal: BMJ (2006)

<i>Research protocols are usually kept confidential to protect intellectual and commercial interests. But secrecy can also hide deviations that affect the validity of results and threaten the integrity of medical research</i>
Impact of systemic immuno-suppression after solid organ transplantation on allergen-specific responses
Authors: T. Eiwegger, S. Gruber, C. Geiger, E. Mayer, E. Dehlink, C. Bannert, T. Frischer, D. Kasper, P. Jaksch, W. Klepetko, C. Akdis, Z. Szépfalusi
Journal: Allergy (2010)

To cite this article: Eiwegger T, Gruber S, Geiger C, Mayer E, Dehlink E, Bannert C, Frischer T, Kasper D, Jaksch P, Klepetko W, Akdis C, Szépfalusi Z. Impact of systemic immuno-suppression after solid organ transplantation on allergen-specific responses. Allergy 2011; 66: 271–278. Introduction: The immunosuppressive therapy in solid organ transplantation targets mainly the T- and B-cell-mediated immune response. However, there is evidence that it neither suppresses sensitization nor clinical manifestation of allergic diseases in organ-transplanted patients. Objective: This study addresses the question whether allergen-specific responses are altered by systemic immunosuppression via negative effects on the T-regulatory cell compartment and a more pronounced suppression on Th1-type T-cell responses. Material and methods: Peripheral blood mononuclear cells from 65 solid organ-transplanted (kidney, liver, lung) children, adolescents, and young adults and 18 healthy, matched controls were included, and their clinical and sensitization status assessed. Allergen-specific proliferation, intracellular cytokine production, frequency of forkhead box P3 (FOXP3)+CD3+CD4+CD25high cells, mRNA expression of IL-10, transforming growth factor (TGF)-β and FOXP3 (real-time RT-PCR) of peripheral blood mononuclear cells or bronchoalveolar lavage fluid (BAL)-derived cells, and the inhibitory capacity of T-reg cells were investigated. Results: Immunosuppression led to a significantly altered regulatory marker profile expressed by enhanced TGF-β mRNA production and a reduced frequency of FOXP3+CD4+CD3+ cells in solid organ transplanted individuals. FOXP3 expression in BAL cells of lung-transplanted patients was significantly decreased. Allergen-specific proliferation was not significantly altered despite long-term immunosuppression. However, suppression of allergen-specific responses via the T-regulatory cell fraction was deficient in immunosuppressed individuals. Conclusion: The results suggest an insufficient control of allergen-specific responses via the Treg-cell compartment under systemic immunosuppression.
Abstract 961: 6-phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumor growth by inhibiting LKB1-AMPK signaling
Authors: Changliang Shan, Shannon E. Elf, Ting-Lei Gu, Hanna J. Khoury, Titus Boggon, Sumin Kang, Jing Chen
Journal: Cancer Research (2014)

Abstract 6-phosphogluconate dehydrogenase (6PGD) in the oxidative pentose phosphate pathway (PPP) is upregulated in many cancers. However, how 6PGD is activated and provides a metabolic advantage to tumor growth is unknown. Here we show that 6PGD is commonly activated in human cancers by acetylation at K76 and K294,We found that 6PGD is commonly activated in human cancers by lysine acetylation. Acetylation at K76 and K294 promotes NADP+-binding to 6PGD and formation of active 6PGD dimers, respectively. Moreover, we found that lysine acetylation of 6PGD is important for cancer cell metabolism, proliferation and tumor growth. We also performed systematic RNAi screens and identified DLAT and ACAT2 as 6PGD acetyltransferases and HDAC4 as 6PGD deacetylase, using two novel “targeted” shRNA libraries that target the majority of acetyltransferases and deacetylases in the human genome, respectively. In addition, we found that 6PGD controls intracellular levels of its product ribulose-5-phosphate (Ru-5-P) to regulate lipogenesis. Ru-5-P inhibits LKB1 by disrupting active LKB1 complex, leading to inhibition of AMPK and subsequent activation of acetyl-CoA carboxylase 1 and lipogenesis. Furthermore, we screened out Physcion and its derivative S3 as novel 6PGD inhibitors, which are efficacious in treatment of xenograft nude mice and primary leukemia cells from human patients with minimal toxicity and no off-target effect. Our findings for the first time decipher the molecular mechanisms underlying 6PGD upregulation in cancer cells and suggest that 6PGD provides an additional and novel link between oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signaling. Moreover, identification and characterization of 6PGD inhibitors in translational/pre-clinical studies for the first time provide “proof of principle” to suggest 6PGD as an attractive anti-cancer target. Citation Format: Changliang Shan, Shannon E. Elf, Ting-Lei Gu, Hanna J. Khoury, Titus Boggon, Sumin Kang, Jing Chen. 6-phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumor growth by inhibiting LKB1-AMPK signaling. [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 961. doi:10.1158/1538-7445.AM2014-961
Adolescents With Depression
Authors: Bernard J Carroll
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
Abstract 13407: A Mouse Model of Heart Failure with Preserved Ejection Fraction (HFpEF) due to Chronic Infusion of a Low Subpressor Dose of Angiotensin II
Authors: Stefano Toldo, Carlo Marchetti, Aysar Al Husseini, Salvatore Carbone, Jessica Regan, Alfonso G Mauro, Andrea Nordio, Chiara Sonnino, Eleonora Mezzaroma, Benjamin W Van Tassell, Antonio Abbate
Journal: Circulation (2014)

Introduction: Heart failure with preserved ejection fracture (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents approximately 50% of all patients with HF, the mechanisms of disease are poorly understood, animal models of HFpEF not due pressure overload are lacking, and therapies for HFpEF are generally ineffective. Hypothesis: A continuous infusion of low dose of angiotensin II (ATII) may be sufficient to induce changes in left ventricular (LV) diastolic function without increasing blood pressure nor induce LV hypertrophy. Methods: Osmotic pumps were implanted subcutaneously in 8 week-old CD1 male mice randomly assigned to the ATII (200 ng/kg/day) or vehicle (N=8/group). Transthoracic echocardiography was performed at baseline and 4 weeks to measure LV dimensions, systolic and diastolic function. Aortic systolic and diastolic pressures (AoP), LV peak systolic and end-diastolic pressures (LVPSP, LVEDP) were measured at LV catheterization. Fibrosis was measured using Masson’s trichrome stain. The expression of Interleukin (IL)-18 mRNA levels, a cytokine associated with impaired cardiomyocyte relaxation, was measured at 4 weeks. Results: When compared to the baseline values or vehicle group, ATII infusion had no effects on AoP, LVPSP and HR, and had no effects on LV dimensions or mass, nor on LVEF (all P&gt;0.2). ATII induced a significant impairment in LV diastolic function as measured by an increase (worsening) of the myocardial performance index (MPI), the LV isovolumetric relaxation time (IVRT) and of LVEDP (Figure). Cardiac expression of IL-18 mRNA was significantly increased 7-fold after ATII infusion (P&lt;0.001), suggesting a potential mechanistic role of IL-18. Conclusion: Chronic infusion of low dose ATII recapitulates the HFpEF phenotype in the mouse, without increasing blood pressure. The use of this mouse model may help understanding the mechanisms leading to HFpEF syndrome in patients.
Abstract 985: The mutational landscape of LN metastasis and recurrence in HNSCC
Authors: Matthew Louis Hedberg, Gerald Goh, Maria Freilino, Yan Zeng, Vivian W. Lui, Roy S. Herbst, Richard P. Lifton, Jennifer R. Grandis
Journal: Cancer Research (2014)

Abstract Recent whole exome sequencing (WES) studies have reported the mutations that characterize primary head and neck squamous cell carcinomas (HNSCC). While exposure to tobacco, alcohol and HPV infection are known to contribute to HNSCC development and prognosis, the largest obstacle to long term survival is recurrent and metastatic disease. Approximately 50% of patients present with synchronous lymph node metastases (SLNM), where 5-year adjusted survival is ≈85% for patients without SLNM compared with 30-60% in patients with SLNM. 20-30% of patients cured of their primary HNSCC go on to develop recurrent disease, which is usually refractory to standard therapies. Here, we report the first WES study of paired primary tumor and SLNM from 14 HNSCC patients, and paired primary tumor and metachronous loco-regional metastases (MLRM) from 11 HNSCC patients. Primary tumors averaged 67 nonsynonymous mutations per tumor (n=21), SLNM averaged 89.3 (n=12), and MLRM averaged 41.7 (n=9). TP53 was the only gene mutated in a majority (57%) of primary tumors in our cohort. We observed similar rates of mutation in several of the TCGA-defined “HNSCC signature” genes in our primary cohort, including FAT1 (14.3%) and CASP8 (4.8%), among others. While the size of our cohort does not allow for appropriately powered statistical analyses; 206 and 204 genes, were mutated in metastatic tumors, but not the respective paired primary tumors, in the SLNM and MLRM cohorts, respectively. AP2B1 and ITPR3 mutations were enriched in SLNM, as newly acquired mutations were seen in multiple (2 and 2/12) SLNM samples. GLUL and DDR2 mutations were enriched in MLRM, as newly acquired mutations were seen in multiple (2 and 2/9) MLRM samples. All 4 genes have previously been implicated in the metastatic process in other cancers. The potential enrichment of DDR2 mutations in HNSCC metastases is especially intriguing, as mutations in this gene have been shown to confer sensitivity to the SRC-family kinase inhibitor, dasatinib, in lung and breast cancer. Here we report exquisite sensitivity to dasatinib in our HNSCC preclinical models harboring DDR2 mutations, suggesting further investigation of this drug is warranted in recurrent HNSCC. Citation Format: Matthew Louis Hedberg, Gerald Goh, Maria Freilino, Yan Zeng, Vivian WY Lui, Roy S. Herbst, Richard P. Lifton, Jennifer R. Grandis. The mutational landscape of LN metastasis and recurrence in HNSCC. [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 985. doi:10.1158/1538-7445.AM2014-985
Abstract 15597: Acute Venous Congestion Causes Angiotensin II formation via Angiotensin-Converting Enzyme Activation in Compensated Ambulatory Patients with Systolic Heart Failure
Authors: Ka Yuk Wong, Yacki Hayashi, Duygu Onat, Ante Harxhi, Michiyori Wakabayashi, Myra M Ahmad, Nir Uriel, Ulrich P Jorde, Ryan T Demmer, Paolo C Colombo
Journal: Circulation (2014)

Background: Plasma levels of angiotensin II (AII) are increased in congestive states such as heart failure (HF). The current study examined i) whether venous congestion (VC) itself promotes AII formation, and ii) the contributions of angiotensin-converting enzyme (ACE) vs. other enzymes such as chymases to AII generation in patients with systolic HF. Methods: 42 ambulatory patients with NYHA functional class II or III, an LVEF &lt;40%, no evidence of VC on physical exam and on stable medical therapy were studied. To experimentally model VC, venous arm pressure was increased to 30 mmHg above baseline by inflating a pressure cuff around the dominant arm. Blood was sampled from test and control arm (lacking an inflated cuff) before and after 90 minutes of VC. Radioimmunoassay was used for plasma AII measurements.The effect of ACE inhibitor (ACEI) based therapy (N=29) vs. non-ACEI (N=13) was compared. Results: The age of the study cohort was 53±12 years, 29% were female, 31% had an ischemic etiology and the LVEF was 22±8%. Baseline AII levels were 3-times lower in the ACEI vs. non-ACEI group (24±10 vs. 76±40 pg/mL, P&lt;0.001). Plasma AII was significantly higher in the congested over control arm only in non-ACEI group after 90 minutes of VC (figure). No adverse event was observed during the test. Conclusions: Our study provides the first direct evidence that VC is sufficient to cause AII formation in compensated ambulatory HF patients on non-ACEI based therapy. ACEI treatment completely abolished this increase suggesting activation of ACE, rather than other enzymes such as chymases, to be the cause of volume-dependent AII formation in response to peripheral VC.
Abstract 19320: Protein Kinase G Oxidation Blunts Its Suppression of Cardiac Hypertrophy by Diminishing Phosphorylation of Tuberin and Consequent Autophagy
Authors: Mark J Ranek, Taishi Nakamura, Ronald Holewinski, Dong-ik Lee, Guangshuo Zhu, Khalid Chakir, Philip Eaton, Jennifer Van Eyk, David A Kass
Journal: Circulation (2014)

Stimulation of protein kinase G (PKG) suppresses maladaptive cardiac hypertrophy in part by blunting signaling cascades such as calcineurin/NFAT (Cn) and calcium-calmodulin dependent kinase II (CamKII). Here we report PKG stimulation also enhances autophagy as an anti-hypertrophic mechanism, identify a novel phosphorylation target for this effect, and show this signaling is blunted when PKG becomes oxidized at cysteine 42 (C42). Mice with knock-in expression of mutant PKG (C42S) or littermate controls were subjected to pressure-overload. C42S mice were protected, with reduced hypertrophy and fibrosis, improved function, and blunted Cn, CamKII, and hypertrophic gene activation. Neonatal rat ventricular myocytes (NRVMs) expressing C42S-PKG exposed to 48hr endothelin-1 (ET1) also displayed less hypertrophic responses. In both C42S mice and NRVMs expressing C42S, autophagic flux was increased over WT, determined by autophagic flux assays, which was associated with inhibited mammalian target of rapamycin (mTOR) signaling. Control mice improved responses similar to C42S mice if autophagic flux was stimulated by inhibiting mTOR with everolimus. Analogous findings were obtained by mTOR suppression in NRVMs. To determine how PKG activation influences mTOR-regulated autophagy, we performed unbiased phospho-proteome analysis using mass spectrometry that revealed a unique PKG targeted site on tuberin (TSC2) at S1343. To test the functional importance of this site, we expressed a mutated TSC2, serine to glutamic acid (phospho-mimetic, S1343E), which depressed mTOR signaling, increased autophagic flux, and blunted hypertrophic signaling and cell enlargement stimulated by ET1 in NRVMs. By contrast, the cardio-protection elicited by PKG C42S was lost when TSC2 or a downstream critical autophagy protein, ATG5 were silenced. Taken together, these results provide the first evidence that PKG activation augments autophagy via targeting of TSC2 as a mechanism of anti-hypertrophic signaling, and that this occurs much more when PKG is in a reduced state (e.g. no C42-disulfide). Loss of this mechanism in myocardium under oxidative stress may play a role in the decline in protection from PKG in cardiac disease which often involves an oxidative environment.
Biological Studies on a Lymphoid-Leukemia Virus Extracted From Sarcoma 37. I. Origin and Introductory Investigations&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: John B. Moloney
Journal: JNCI Journal of the National Cancer Institute (1960)

Journal Article Biological Studies on a Lymphoid-Leukemia Virus Extracted From Sarcoma 37. I. Origin and Introductory Investigations Get access John B. Moloney John B. Moloney Laboratory of Biology, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 24, Issue 4, April 1960, Pages 933–951, https://doi.org/10.1093/jnci/24.4.933 Published: 01 April 1960 Article history Received: 01 September 1959 Published: 01 April 1960
Abstract 18576: Hypoxia Induces Phenotypic Switching of Human Pericytes Into Smooth Muscle Cells That is Associated With Changes in Pericyte-specific Non-coding RNA Expression
Authors: Christoph M Zehendner, Shemsi Demolli, Katharina Michalik, Nicolas Jaé, Jasmin Wagner, David John, Shizuka Uchida, Andreas M Zeiher, Stefanie Dimmeler
Journal: Circulation (2014)

Background: Pericytes are pivotal for endothelial barrier integrity, angiogenesis, organ function and wound healing. While endothelial hypoxic reponses are well explored, knowledge on the effects of hypoxia on human pericytes (hPC) is sparse. Non-coding RNAs (ncRNAs) control gene expression by various mechanisms, but their functions in hPC remain unknown. We hypothesized that hypoxia influences the hPC-specific transcriptome and hPC phenotype. Methods: hPC were validated by analyzing established pericyte expression markers via qRT-PCR and immunofluorescence (IF). Subsequently, hPC and HUVEC were subjected towards hypoxia (24h 1%O 2 ), and next generation RNA deep sequencing (RNAseq) was performed. hPC viability following hypoxia was analyzed by CalceinRed assay. Results: hPC expressed specific pericyte markers (Desmin, NG2, alphaSMA, PDGFRb) on mRNA and protein level. Cell viability of hPC was not affected by hypoxia. RNAseq revealed that 109 coding genes are significantly regulated in both HUVEC and hPC, whereas 520 coding genes were significantly regulated specifically in hPC (P&lt;0.05, n=3). Interestingly, we identified a number of smooth muscle cell (SMC)-related genes that were increased in hypoxic hPC. The increase of the prototypic SMC marker alphaSMA was confirmed by qRT-PCR (2.23±1.18 fold induction) and IF. We observed a significant regulation of 6 ncRNAs, which were commonly regulated in HUVEC and in hPC, including the known hypoxia-induced miR-210 cluster (HUVEC: 7.86±0.09; hPC: 7.1±0.72 fold induction). Further 36 hPC-specific ncRNAs were identified, among them 25 long intergenic ncRNAs (lincRNAs) and 10 antisense RNAs (P&lt;0.05,n=3). Notably, lincRNA H19, that is known to be important for muscle cell differentiation, was strongly upregulated in hypoxic hPC (4.24±1.1 fold induction, P&lt;0.001,n=3). Conclusion: Hypoxia triggers hPC differentiation towards a SMC phenotype that is associated with a significant change in hPC-specific ncRNA expression without affecting hPC viability. The functions of the newly identified ncRNAs are currently investigated. Our findings may be relevant to understand the role of pericytes in persistent vascular constriction and vessel destabilization in stroke or myocardial infarction.
The Alveolar Macrophage and Acute Respiratory Distress Syndrome
Authors: Laura Barr, Mairi Brittan, Andrew Conway Morris, Daniel F. McAuley, Chiara McCormack, Alison M. Fletcher, Hamish Richardson, Martin Connell, Dilip Patel, William A. H. Wallace, Adriano Rossi, Donald J Davidson, Lynn Manson, Marc Turner, Nikhil Hirani, Timothy Walsh, Niall Anderson, Kevin Dhaliwal, John Simpson
Journal: American Journal of Respiratory and Critical Care Medicine (2014)