tbuckley/cabot-search huggingface dataset:
Abstract 2629: PIK3CA mutation promotes tumor cell invasion and migration independently from AKT and mTOR kinase in cancer cells.
Authors: Bhaskar Bhattachara, Enrico Stasik, Sarah Low, Andrea Sturz, Christoph Schatz, Richie Soong, Ningshu Liu
Journal: Cancer Research (2013)

Abstract Although the role of phosphoinositide-3 kinase (PI3K) in promoting tumorigenesis, tumor cell survival, proliferation and metabolism has been extensively evaluated, the mechanisms of other oncogenic processes mediated by PI3K have not been fully addressed. We report here a novel molecular mechanism by which PI3K mediates tumor cell invasion and migration using isogenic cell lines and highly selective PI3K pathway inhibitors. First of all, using a set of MCF10A-derived isogenic cell lines with PIK3CAH1047R, PTEN-deletion, or AKTE17K mutations, we found that activating the PIK3CA mutation, but not PTEN-deletion or AKT mutation, promoted tumor cell migration in a wound healing assay. Treatment of the PIK3CAH1047R isogenic cell line with a highly selective PI3K inhibitor (BAY 80-6946) effectively blocked tumor cell migration. Interestingly, neither allosteric AKT inhibitor nor mTOR kinase inhibitors were able to inhibit PIK3CA-stimulated cell migration although both AKT and mTOR kinase inhibitors potently inhibited AKT phosphorylation in these cells. In contrast, AKT inhibition enhanced the migration of PIK3CA mutant isogenic cells. This result revealed a novel AKT- and mTOR-independent mechanism by which activating PI3K mutation stimulates tumor cell migration. This conclusion was further confirmed in a panel of gastric cancer cell line in both wound healing and migration assays. Additional mechanistic experiments are being performed to examine downstream signaling events and will be presented. Taken together, these data suggest a role of PI3K in contributing to tumour metastasis independent of the canonical PI3K-AKT-mTOR axis and further validation of using AKT inhibitor for the treatment of metastatic PIK3CA mutant tumors to be conducted. Citation Format: Bhaskar Bhattachara, Enrico Stasik, Sarah Low, Andrea Sturz, Christoph Schatz, Richie Soong, Ningshu Liu. PIK3CA mutation promotes tumor cell invasion and migration independently from AKT and mTOR kinase in cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2629. doi:10.1158/1538-7445.AM2013-2629
A Greenock Family Doctor Looks Back Seven Years
Authors: J. H. Henderson
Journal: BMJ (1965)

After five years', hospital service and one year as a trainee assist- ant in general practice, I decided, at the age of 35, to put "1my plate up " in the Larkfield district of Greenock., Renfrewshire, three miles from the town centre.A temporary surgery was built and proved sufficient for the first five years.It was sectional., wooden., cost about £550., and was paid for in cash.. Home was a rented furnished house for' the first 18 months, and for the five years 'after that it was a small bought bungalow.It can fairly be said that the doctor and his wife and daughter lived modestly.
Lack of Microsomal Prostaglandin E <sub>2</sub> Synthase-1 in Bone Marrow–Derived Myeloid Cells Impairs Left Ventricular Function and Increases Mortality After Acute Myocardial Infarction
Authors: Norbert Degousee, Jeremy Simpson, Shafie Fazel, Klaus Scholich, Denis Angoulvant, Carlo Angioni, Helmut Schmidt, Marina Korotkova, Eva Stefanski, Xing-Hua Wang, Thomas F. Lindsay, Efrat Ofek, Sandra Pierre, Jagdish Butany, Per-Johan Jakobsson, Armand Keating, Ren-Ke Li, Matthias Nahrendorf, Gerd Geisslinger, Peter H. Backx, Barry B. Rubin
Journal: Circulation (2012)

Microsomal prostaglandin E(2) synthase-1 (mPGES-1), encoded by the Ptges gene, catalyzes prostaglandin E(2) biosynthesis and is expressed by leukocytes, cardiac myocytes, and cardiac fibroblasts. Ptges(-/-) mice develop more left ventricle (LV) dilation, worse LV contractile function, and higher LV end-diastolic pressure than Ptges(+/+) mice after myocardial infarction. In this study, we define the role of mPGES-1 in bone marrow-derived leukocytes in the recovery of LV function after coronary ligation.Cardiac structure and function in Ptges(+/+) mice with Ptges(+/+) bone marrow (BM(+/+)) and Ptges(+/+) mice with Ptges(-/-) BM (BM(-/-)) were assessed by morphometric analysis, echocardiography, and invasive hemodynamics before and 7 and 28 days after myocardial infarction. Prostaglandin levels and prostaglandin biosynthetic enzyme gene expression were measured by liquid chromatography-tandem mass spectrometry and real-time polymerase chain reaction, immunoblotting, immunohistochemistry, and immunofluorescence microscopy, respectively. After myocardial infarction, BM(-/-) mice had more LV dilation, worse LV systolic and diastolic function, higher LV end-diastolic pressure, more cardiomyocyte hypertrophy, and higher mortality but similar infarct size and pulmonary edema compared with BM(+/+) mice. BM(-/-) mice also had higher levels of COX-1 protein and more leukocytes in the infarct, but not the viable LV, than BM(+/+) mice. Levels of prostaglandin E(2) were higher in the infarct and viable myocardium of BM(-/-) mice than in BM(+/+) mice.Lack of mPGES-1 in bone marrow-derived leukocytes negatively regulates COX-1 expression, prostaglandin E(2) biosynthesis, and inflammation in the infarct and leads to impaired LV function, adverse LV remodeling, and decreased survival after acute myocardial infarction.
4.8 Role of Toll-like receptor 9 in the pathogenesis of inflammatory autoimmune arthritis and osteoclast activation
Authors: Anita Fischer, Christina Böhm, Victoria Saferding, Eliana Goncalves-Alves, Roman Kreindl, Marije Koenders, Wim van den Berg, Tobias Rothe, Gerhard Krönke, Diana Dudziak, Günter Steiner
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> There is some evidence that release and insufficient removal of endogenous nucleic acids may be involved in triggering harmful autoimmune reactions that might be important in the initiation of RA. Nucleic acid-sensing molecules, such as the endosomal Toll-like receptors (TLRs) 7 and 9, have been linked to pathogenic autoimmune processes, particularly in SLE, but their role in RA is less clear. Data recently obtained in rats with pristane-induced arthritis (PIA) suggested involvement of TLR9, because antagonizing this receptor in the initiation phase of the disease led to an improved clinical outcome of arthritis. To gain more insight into the role of TLR9 in autoimmune arthritis we have extended our studies to the K/BxN serum-transfer arthritis model which is reflecting the effector phase of erosive autoimmune arthritis. <h3>Materials and Methods</h3> Arthritis was induced in C57BL/6 mice by two subsequent injections of arthritogenic serum. Antagonists for TLR7 and TLR9 or an agonist for TLR9, respectively, a non-inhibitory control sequence or PBS as placebo was applied every third day. The first treatment was given one day before disease induction. To further investigate TLR9 involvement, arthritis was also induced in TLR9 knock-out mice. Furthermore, the effect of TLR9 on osteoclast differentiation and activation was investigated in an <i>in vitro</i> osteoclast formation assay. <h3>Results</h3> Neither inhibitor affected arthritis onset and severity in the serum transfer model, which is independent of the adaptive immune system, in contrast to PIA. Furthermore, arthritis severity was not changed in mice lacking a functional tlr9 gene in comparison to wild type animals. In contrast, treatment with a TLR9 agonist led to an improved clinical outcome. Remarkably, in vitro formation of osteoclasts appeared to be slightly enhanced in cells isolated from TLR9-/- mice compared to those from wild type animals. Moreover, osteoclastogenesis was reduced by ~60% in cells from wild type animals grown in the presence of the TLR9 agonist whereas, as expected, no effect was seen in cells from TLR9-/- animals. <h3>Conclusions</h3> These results suggest that TLR9 might play a beneficial regulatory role in the effector phase of erosive autoimmune arthritis by negatively affecting differentiation and activation of bone resorbing osteoclasts. Nevertheless, the precise role of TLR9 in the different stages of arthritis needs to be further elucidated.
Using biomarkers of genetic susceptibility to enhance the study of cancer etiology.
Authors: N Rothman, R B Hayes
Journal: Environmental Health Perspectives (1995)

There has been increasing interest in the interaction of genetic susceptibility and xenobiotic exposures in cancer etiology. Study of gene-environment interactions may increase our ability to characterize relatively low population risks if a substantial proportion of the population cancer burden is attributed to high risk among a smaller group of genetically susceptible members. Further, these studies may provide insight into the mechanism of carcinogenesis, which can help establish the biologic plausibility of an exposure-cancer relationship. Biologic processes important in tumorigenesis that exhibit substantial interindividual differences may function as susceptibility factors. Potential examples include polymorphic enzymes, which activate and detoxify procarcinogens and carcinogens (e.g., certain P450 enzymes, N-acetyltransferase [NAT2], glutathione S-transferase M1), and variation in the capacity to repair DNA. Biologic assays are now available to evaluate many of these functions at the DNA and phenotype level and can be readily incorporated into studies of cancer etiology.
Isn’t This Just Snacking? The Potential Adverse Effects of Night-Eating Symptoms on Treatment Adherence and Outcomes in Patients With Diabetes
Authors: Katsunori Nonogaki, Kyoko Tateishi, Naohiko Nonogaki
Journal: Diabetes Care (2007)

As reported by Morse et al. (1), night-eating syndrome (NES) is likely to produce an adverse outcome in patients with type 2 diabetes. NES is defined as a circadian delay in daily food intake distinguished by evening hyperphagia (25% daily food intake consumed after the evening meal) and/or nighttime awakenings to eat at least three times per week (2). In addition to eating greater amounts of food in the evening hours, patients with NES often choose disproportionately large quantities of fat- …
Prejudgement towards the quality of spirometry in primary care does not help our case
Authors: N. H. Chavannes, T. R. J. Schermer
Journal: European Respiratory Journal (2006)

To the Editors: 

We very much appreciate the contribution by Zielinski et al. 1 on the topic of early detection of chronic obstructive pulmonary disease (COPD) by high-risk population screening in the April issue of the European Respiratory Journal . The authors mention that “insufficient quality of spirometries performed in the primary care setting was also reported recently by Schermer et al.” We were quite surprised to notice that …
Dying to Live
Authors: Eric G. Anderson
Journal: JAMA (1992)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Newcastle-on-Tyne Infirmary: Senile Gangrene, followed by Tetanus
Authors: None Taylor
Journal: BMJ (1841)

FEMALE GANGRENE.-DISLOCATIONOF FEMUR.245 this appeared to have enitirely lost their normal character.Each ventiicle contained about half an ounce of serum.There was nothing unusual found ill the rest of the brain.The liver and kidneys were much congested with blood.In the spleen, wbich was more than twice its usual size, was found a clot of extravasated blood, exceedingly firm, and of a pale yellow colour.IL was situated immediately below the surface of its cbnvex margin.The mucous membrane of the colon was in several places destroyed by ulceration.
Bowel ultrasound in assessment of Crohn's disease and detection of related small bowel strictures: a prospective comparative study versus x ray and intraoperative findings
Authors: F Parente
Journal: Gut (2002)

Background and aim: Despite the fact that bowel ultrasound (US) has recently been proved to be useful in the assessment of bowel diseases, uncertainty persists as to its diagnostic role in patients with complicated Crohn9s disease (CD). Therefore, we have prospectively investigated the accuracy of US compared with <i>x</i> ray procedures and intraoperative findings in detecting small bowel strictures complicating CD as well as its reliability in assessing disease extent and location within the bowel. Methods: A series of 296 consecutive patients with proven CD admitted to L Sacco University Hospital between 1997 and 1999, having undergone complete radiographic evaluation (including small bowel <i>x</i> ray, colonoscopy, or double contrast barium enema), were enrolled in the study. Bowel US was performed in each patient by two experienced operators unaware of the results of other diagnostic procedures. The accuracy of US in detecting strictures compared with <i>x</i> ray studies was determined separately in two different groups of patients: 211 patients treated conservatively (non-operative CD) and 85 patients who were candidates for surgery for CD complications or unresponsiveness to medical therapy (operative CD). Results: Overall sensitivity and specificity of US in assessing the anatomical distribution of CD were 93% and 97%, respectively. The extent of ileal disease measured at US correlated well with that determined by <i>x</i> ray (<i>r</i>=0.52, p&lt;0.001) in medically treated patients as well as with that measured intraoperatively in surgical patients (<i>r</i>=0.64, p&lt;0.001). One or more stenoses were detected in 75 patients (35.5%) at small bowel enteroclysis in the non-operative CD group compared with 70 (82%) in the operative CD series. Sensitivity, specificity, and positive predictive values of bowel US in the detection of strictures were 79%, 98%, and 95% in non-operative CD patients and 90%, 100%, and 100% in operative CD cases, respectively. Conclusions: In experienced hands, bowel US is an accurate technique for assessing CD extent and location and is very helpful in detecting small bowel strictures, especially in very severe cases that are candidates for surgery. The use of bowel US is therefore justified as a primary investigation in CD patients in whom complications are suspected.
Synergism between muramyl dipeptide and lipopolysaccharide in the inhibition of glycosaminoglycan synthesis in cultured rat costal chondrocytes.
Authors: T Ikebe, M Hirata, F Yanaga, T Koga
Journal: Annals of the Rheumatic Diseases (1993)

The effect of synthetic muramyl dipeptide on glycosaminoglycan synthesis in cultured rat costal chondrocytes was examined. Muramyl dipeptide alone had no effect on the glycosaminoglycan synthesis of rat chondrocytes, whereas Escherichia coli lipopolysaccharide and interleukin 1 alpha inhibited glycosaminoglycan synthesis in a dose dependent manner. Muramyl dipeptide, when added to chondrocyte cultures in the presence of lipopolysaccharide, enhanced the lipopolysaccharide induced inhibition of glycosaminoglycan synthesis in a dose dependent manner. Adjuvant active analogues of muramyl dipeptide, but not adjuvant inactive analogues, also enhanced the lipopolysaccharide induced inhibition of glycosaminoglycan synthesis. In combination with muramyl dipeptide, to inhibit glycosaminoglycan synthesis, lipopolysaccharide could be replaced with the synthetic lipid A, an active principle of lipopolysaccharide. These results show that the muramyl dipeptide portion of bacterial peptidoglycan enhances the susceptibility of rat chondrocytes to the lipid A portion of bacterial lipopolysaccharide, and therefore the interaction between chondrocytes and bacterial cell wall components might be involved in damaging the cartilage in inflammatory joint diseases.
THE ADVANTAGES OF THE KNEE-CHEST POSTURE IN SOME OPERATIONS UPON THE VESICAL END OF THE URETERS.
Authors: HOWARD A. KELLY
Journal: JAMA (1902)

On May 20, 1901, I presented for the consideration of the Johns Hopkins Medical Society a brief paper<sup>1</sup>entitled "A New and Better Method of Opening and of Draining the Bladder in Women." The method advocated consists in placing the patient in the knee-breast posture and then letting air into the bladder through a catheter or a speculum. If the posterior vaginal wall is now lifted up so as to expose the entire anterior vaginal wall from cervix to urethra, a suitably curved knife may be plunged through the vesico-vaginal septum into the air-distended bladder, and if the knife is sharpened on both edges the cut can easily be lengthened fore and aft from the cervix to the urethra, if it is desirable to make such a large incision. An artificial anemia of the bladder is induced by this posture and whatever blood escapes from the cut runs down
Polytetrafluoroethylene Graft Survival in Hemodialysis
Authors: Rino Munda
Journal: JAMA (1983)

Expanded polytetrafluoroethylene (PTFE) graft fistulas are widely used as secondary vascular access for patients receiving long-term hemodialysis treatment. Sixty-seven grafts were implanted in 48 patients and followed for 12 to 51 months. Cumulative patency for all grafts at 12 months was 67% +/- 6%, at 24 months 50% +/- 7%, and at 48 months 43% +/- 9%. Graft survival rates were different when considering graft configuration and location. Forearm straight graft survival at 12 months was 35% +/- 13%, upper arm curved grafts 60% +/- 19%, and forearm looped grafts 78% +/- 7%. Complications that decreased graft survival were related to thrombosis (21%), infection (25%), and intimal hyperplasia at the venous anastomosis (34%). After reviewing our experience, we believe that the challenge of secondary vascular access has not been solved by PTFE grafts. This should stimulate the search for better grafts and techniques.
A Report of the Causes of Blindness in 111 Inmates of, or Workers at, the Sheefield Institution for the Blind, with Remarks
Authors: S. Snell
Journal: BMJ (1886)

CASE ivi.-The following is a case in which the drill might, no doubt, have been successfully employed, but in which the nature of the exostosis admitted the use of a readier means of extirpation.The patient was sent up from the country to thc George Bird Ward, St. Mary's Hospital.I fouind that he had for years, on and off, suffered irom discharge from the left ear, and that he had latterly complained of great pain on-the left side of the head.The meatus, as examina- tion with a probe revealed, was completely occupied by a large and apparently fixed spongy osteoma.Directly the patient was well
Clinical and Immunologic Features of Infants in an Observational Study (CoFAR) who were Selected for an Increased Risk to Develop Peanut Allergy (PNA)
Authors: R WOOD, S JONES, A BURKS, A LIU, D FLEISCHER, D LEUNG, J ULLAH, D STABLEIN, R LINDBLAD, H SAMPSON
Journal: Journal of Allergy and Clinical Immunology (2008)
Ga-67 and Tc-99m (V) DMSA Imaging in Non-Hodgkin??s Lymphoma With Amyloid Tumor
Authors: HITOYA OHTA, NOBUYOSHI ARIMA, YOKO HAMA, SHOUICHI DOI, KAORU NASI, TOMOO KOMIBUCHI, MASAYUKI SHINTAKU
Journal: Clinical Nuclear Medicine (1995)

This report describes the localization and categorization of tumors using Ga-67 and Tc-99m (V) DMSA imaging in a rare case of non-Hodgkin's lymphoma associated with an amyloid tumor. Ga-67 uptake was found in both the lymphoma and the amyloid tumor. Significant Tc-99m (V) DMSA uptake was found only in the amyloid tumor. In this case, Ga-67 uptake was nonspecific, but Tc-99m (V) DMSA uptake gave additional information before treatment.
Non-alcoholic steatohepatitis: A non-invasive diagnosis by analysis of exhaled breath
Authors: Froukje J. Verdam, Jan W. Dallinga, Ann Driessen, Charlotte de Jonge, Edwin J.C. Moonen, Joep B.N. van Berkel, Jakobus Luijk, Nicole D. Bouvy, Wim A. Buurman, Sander S. Rensen, Jan Willem M. Greve, Frederik Jan van Schooten
Journal: Journal of Hepatology (2012)
Possible involvement of inefficient cleavage of preprovasopressin by signal peptidase as a cause for familial central diabetes insipidus.
Authors: M Ito, Y Oiso, T Murase, K Kondo, H Saito, T Chinzei, M Racchi, M O Lively
Journal: Journal of Clinical Investigation (1993)

A transition of G to A at nucleotide position 279 in exon 1 of the vasopressin gene has been identified in patients with familial central diabetes insipidus. The mutation predicts an amino acid substitution of Thr (ACG) for Ala (GCG) at the COOH terminus of the signal peptide in preprovasopression (preproVP). Translation in vitro of wild-type and mutant mRNAs produced 19-kD preproVPs. When translated in the presence of canine pancreatic rough microsomes, wild-type preproVP was converted to a 21-kD protein, whereas the mutant mRNA produced proteins of 21 kD and 23 kD. NH2-terminal amino acid sequence analysis revealed that the 21-kD proteins from the wild-type and the mutants were proVPs generated by the proteolytic cleavage of the 19-residue signal peptide and the addition of carbohydrate. Accordingly, mutant preproVP was cleaved at the correct site after Thr-19, but the efficiency of cleavage by signal peptidase was < 25% that observed for the wild-type preproVP, resulting in the formation of a predominant glycosylated but uncleaved 23-kD product. These data suggest that inefficient processing of preproVP produced by the mutant allele is possibly involved in the pathogenesis of diabetes insipidus in the affected individuals.
Isosorbide Dinitrate During Acute Coronary Occlusion
Authors: Edward L. Seljeskog
Journal: JAMA (1963)

THE USE OF coronary vasodilators in the treatment of acute myocardial infarction has been considered by some authors to be physiologically unsound, since hypotension frequently accompanies their use.<sup>1</sup>Seemingly, if a specific coronary vasodilator were available to adequately dilate coronary vessels without an associated systemic hypotension, such a drug would be both beneficial and useful. The supply of oxygenated blood provided to a region of ischemic myocardium through collaterals probably could be increased, and the danger of ventricular fibrillation lessened. In spite of the paradoxical lowering of blood pressure with the use of nitrates, a few authors continue to advocate their use in humans during acute myocardial infarction. Isosorbide dinitrate (Isordil) is claimed to be a potent coronary vasodilator, and, because of its rapid absorption and prolonged action appears potentially more useful than some other nitrates.<sup>2,3</sup> Hedges et al<sup>4</sup>recently suggested possible benefits with isosorbide dinitrate in