tbuckley/cabot-search huggingface dataset:
Abstract 3678: Combination analysis of oncogenic mutations and signaling pathway proteins identifies effective therapeutic targets in colorectal cancers
Authors: Jeeyun Lee, Phillip S. Kim, Tani Lee, Anne Kuller, Fred Princen, Sharat Singh, Hee C. Kim
Journal: Cancer Research (2012)

Abstract Despite overall improvements in colorectal cancer (CRC) therapies, an understanding of reasons for therapeutic response/non-response as well as disease recurrence remains poor. Currently, the gold standard for CRC prognosis remains the clinicopathological staging of tumors. Addition of molecular markers for predicting prognosis and therapeutic outcomes can significantly enhance the clinical managements of CRCs. A comprehensive molecular characterization of 116 stages I to IV Asian CRC patients that also included 2 paired normal samples and 19 hepatic metastases of which 10 were from paired primary tumor samples (total 136 specimens) was performed. Somatic mutational analysis scored for 12 different mutations resident within the KRAS, BRAF and PIK3CA oncogenes alongside a parallel determination of kinase activation profiles for HER1, HER2, HER3, c-MET, IGF1R, PI3K, Shc, AKT and ERK using the multiplexed Collaborative Enzyme Enhanced Reactive (CEER™) immunoassay. CEER is a highly sensitive and specific proximity assay that relies on the formation of a triple antibody complex surrounding the target protein. Various mutations of KRAS and BRAF were found in 41% (48/116) and 4% (5/116) of patients, respectively. Incidence of PIK3CA mutations were 11% (13/116) in this cohort. Overall, KRAS G12D and G13D mutations were the most frequent in this cohort. Several primary as well metastatic CRCs with KRAS mutations demonstrated a second mutation in the PIK3CA gene. While both ErbB-driven and non-ErbB-driven pathway signatures were observed in this cohort, there was no apparent correlation found between the KRAS mutational status of the tumors and the activation status of the downstream/upstream pathway signals. Molecular characterization of CRC samples for oncogenic mutations should be complemented with functional pathway profiling to pinpoint potential therapeutic target(s). The tumor's dependence on specific pathway cannot be predicted based on mutations alone hence it is critical to also evaluate pathway activation for selecting more effective clinical strategy. Our study also demonstrated modulation in signaling pathways concomitant with disease recurrence. Such clinical validations and comprehensive molecular profiles of CRC tumors can allow for the implementation of these companion biomarkers in CRC therapeutic clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3678. doi:1538-7445.AM2012-3678
FOUR-YEAR RESULTS OF THE PLATINUM RANDOMIZED TRIAL: CAN STENT METAL ALLOY COMPOSITION AND DESIGN AFFECT LATE CLINICAL OUTCOMES?
Authors: Dean Kereiakes, Gregg Stone, Paul Teirstein, Ian Meredith, Gilles Levy, Francois Schiele, Thomas Downes, Dariusz Dudek, Michael Foster, Maurice Buchbinder, Henry Lui, Dominic Allocco, Keith Dawkins
Journal: Journal of the American College of Cardiology (2014)
Is early visual processing attention impenetrable?
Authors: Su-Ling Yeh, I-Ping Chen
Journal: Behavioral and Brain Sciences (1999)

Pylyshyn's effort in establishing the cognitive impenetrability of early vision is welcome. However, his view about the role of attention in early vision seems to be oversimplified. The allocation of focal attention manifests its effect among multiple stages in the early vision system, it is not just confined to the input and the output levels.
Binding of kidney bean (Phaseolus vulgaris) isolectins to differentiated human colon carcinoma Caco-2 cells and their effect on cellular metabolism.
Authors: H G Hendriks, M J Kik, J F Koninkx, T S van den Ingh, J M Mouwen
Journal: Gut (1991)

The binding of Phaseolus vulgaris (PHA) isolectins L4 and E4 to the brush border membrane of differentiated Caco-2 cells was studied and the impact on cellular metabolism and microvilli was assessed. Computer analysis of the data based on binding experiments with peroxidase conjugated isolectins gave mean (SD) values for maximal binding of 2540 (151).10(-9) M for PHA-L4 and 2104 (140).10(-9) M for PHA-E4 per mg of brush border membrane protein. The dissociation constants for L4 and E4 binding were 4.3 (1.4).10(-6) M and 1.1 (0.8).10(-6) M, respectively. Incubation of differentiated Caco-2 cells for 30 minutes with ferritin conjugated PHA isolectins showed that, as indicated by the number of ferritin particles, PHA-E4 bound to the microvilli to a greater extent than PHA-L4. Ferritin particles were also localised intracellularly over endocytotic invaginations and vesicles. After incubation for 48 hours with PHA-L4 or PHA-E4, the relative incorporation of precursors for DNA, RNA, and (glyco)protein synthesis into the trichloroacetic acid insoluble fraction of the Caco-2 cells was determined. Both isolectins stimulated the incorporation of thymidine and glucosamine, but neither PHA-L4 nor PHA-E4 were able to influence the incorporation of uridine. With respect to fucose, methionine, and N-acetyl mannosamine, the stimulatory effect remained confined to PHA-E4. Since PHA-L4 and PHA-E4 were tested at the same concentrations, PHA-E4 is more effective than PHA-L4. The changes in the uptake of radioactive precursors were lost after heat inactivation of PHA-E4. Compared with control and PHA-L4 incubated Caco-2 cells, the microvilli of PHA-E4 incubated cells were shortened significantly (p less than 0.01).
A 5-fluorouracil-loaded polydioxanone weft-knitted stent for the treatment of colorectal cancer
Authors: Gang Li, Yufeng Chen, Jun Hu, Xiaojian Wu, Junyan Hu, Xiaowen He, Jiashen Li, Zheng Zhao, Zexian Chen, Yuling Li, Hong Hu, Yi Li, Ping Lan
Journal: Biomaterials (2013)
Corneal Perforation Caused by Dysgonic Fermenter—2
Authors: Raphael J. Kiel
Journal: JAMA (1987)

<i>DYSGONIC fermenter—2</i>(DF-2) is the Centers for Disease Control designation given to a fastidious gram-negative organism that causes cellulitis, septicemia, meningitis, and endocarditis in man.<sup>1-9</sup>Infections with this agent are frequently associated with dog contact or dog bite, and DF-2 has been shown to be a member of the oral flora of dogs.<sup>10</sup>This organism is oxidase positive, catalase positive, and urease negative and does not grow on MacConkey's agar. Infection with this agent occurs preponderantly in debilitated patients and in patients with splenectomy. To date, to our knowledge, there has been no report of ocular infection with DF-2. We report the case of a man with severe corneal necrosis in which DF-2 was the only organism isolated and the patient's subsequent response to surgical débridement and treatment with ceftizoxime sodium. <h3>Report of a Case</h3> A 62-year-old man was seen at the Kresge Eye Clinic of Wayne State
Axe the 55 payment for dementia diagnosis, say doctors
Authors: Z. Kmietowicz
Journal: BMJ (2014)

Leading doctors and health campaigners have written an open letter to NHS leaders calling for the withdrawal of a new scheme that pays GPs in England £55 (€70; $90) for every new diagnosis of dementia over the next five months.

The letter to Simon Stevens, chief executive of NHS England, and Alistair Burns, national clinical lead for dementia, acknowledges that diagnosing dementia is “a …
National obesity strategy: what's the big idea?
Authors: Nigel Hawkes
Journal: BMJ (2008)

<h3>Objective</h3> To investigate the clinicopathologic features of eosinophilic granulomatosis with polyangiitis (EGPA)–associated neuropathy with a focus on the presence or absence of anti-neutrophil cytoplasmic antibodies (ANCAs). <h3>Methods</h3> We examined the clinical features and pathologic findings of sural nerve biopsy specimens from 82 patients with EGPA-associated neuropathy. Of these patients, 32.9% were myeloperoxidase (MPO)-ANCA positive, and 67.1% were MPO-ANCA negative. PR3-ANCA was negative in all of 78 examined patients. <h3>Results</h3> Upper limb symptoms were more frequently reported as initial neuropathic manifestations in the MPO-ANCA–positive group than in the MPO-ANCA–negative group (44.4% vs 14.6%, <i>p</i> &lt; 0.01). The serum levels of C-reactive protein were significantly higher in the MPO-ANCA–positive group than in the MPO-ANCA–negative group (<i>p</i> &lt; 0.05). Sural nerve biopsy specimens showed findings suggestive of vasculitis (i.e., destruction of vascular structures) in epineurial vessels; these results were seen more frequently in the MPO-ANCA–positive group than in the MPO-ANCA–negative group (<i>p</i> &lt; 0.0001). Conversely, the numbers of eosinophils in the lumen of the epineurial vessels (<i>p</i> &lt; 0.01) and epineurial vessels occluded by intraluminal eosinophils (<i>p</i> &lt; 0.05) were higher in the MPO-ANCA–negative group than in the MPO-ANCA–positive group. Furthermore, the incidence of eosinophil infiltration in the endoneurium was higher in the MPO-ANCA–negative group than in the MPO-ANCA–positive group (<i>p</i> &lt; 0.01). <h3>Conclusions</h3> This study suggests that the pathogenesis of EGPA comprises at least 2 distinct mechanisms: ANCA-associated vasculitis resulting in ischemic effects and inflammation, which is prominent in MPO-ANCA–positive patients, and eosinophil-associated vascular occlusion leading to ischemia and eosinophil-associated tissue damage, which is conspicuous in MPO-ANCA–negative patients.
AN UNUSUAL CASE OF TRAUMATIC URETHRAL STRICTURE
Authors: J. A. C. COLSTON
Journal: JAMA (1923)

The treatment of injuries to the urethra is one of the most interesting fields of the surgery of the genitourinary tract, and it is well recognized that there are few cases which require a nicer choice of operative procedure and, especially, more careful postoperative treatment, if satisfactory and permanent results are to be obtained. In most of these cases, the diagnosis is, of course, self-evident, and the extent and location of the injury can be accurately determined by simple diagnostic methods, so that the indications for operation are usually quite definite. The aim of the operation should, of course, be complete restoration of function with a minimum of scar tissue formation. Cicatricial contraction along the course of the urethra is very difficult to prevent, and it is the chief cause of the disappointing results which so often follow operation in this type of case. When a recent injury to the
The Doctor/Patient Relationship in Ulcerative Colitis
Authors: H. Freyberger
Journal: Psychotherapy and Psychosomatics (1970)

This contribution deals with some observations concerning the doctor/ patient relationship in ulcerative colitis. At first we describe the specific experience of object loss which arises at the beginning of ulcerative colitis. Following this we report on several patients' groups and the connected object loss experience as well as the doctor/patient relationship. On the basis of these reports the high psychotherapeutic influence of this relationship will be evident. From this we state some valuable points concerning the attitude of doctors and nurses toward their patients during treatment.
Biosafety Concerns Involving Genetically Modified Mosquitoes to Combat Malaria and Dengue in Developing Countries
Authors: Graciela R. Ostera
Journal: JAMA (2011)

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
Who Will Die in the ICU? APACHE II, ROC Curve Analysis, and, of Course, Cleone
Authors: Donald A. Redelmeier
Journal: JAMA (1989)

<h3>To the Editor. —</h3> The article by Kruse et al<sup>1</sup>important contribution to efforts at predicting the survival of patients admitted to medical intensive care units. However, the authors' use of the area under the receiver operating characteristic (ROC) curve to evaluate the predictions is potentially misleading. It is hard to imagine that the ability of clinicians to estimate intermediate probabilities (ie, a 60% mortality) with precision influences clinical action. Only extremely high or extremely low estimates of the probability of dying provide information that might change clinicians' decisions in the intensive care unit.<sup>2</sup>Since a ROC curve is established by many intermediate predictions, the estimates of a mediocre predictor can still generate a relatively large area under the ROC curve and appear to have "good" predictive accuracy, but offer little practical clinical value. The relevance of any predictor of mortality is best evaluated by evaluating the correctness
Hyperhomocysteinemia in Hypothyroidism
Authors: Daniel Weiss
Journal: Annals of Internal Medicine (2000)

Letters18 April 2000Hyperhomocysteinemia in HypothyroidismDaniel Weiss, MDDaniel Weiss, MDCase Western Reserve University School of Medicine; Cleveland, OH 44106 (Weiss)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-8-200004180-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest the article by Hussein and colleagues (1) on hyperhomocysteinemia in patients with hypothyroidism. The authors also report normalization of elevated homocysteine levels after attainment of the euthyroid state. I suggest a potential mechanism for these alterations that was not mentioned in the article.Reductions in glomerular filtration rate (GFR) have been well documented in patients with hypothyroidism, as have increases in GFR in hyperthyroid patients (2, 3). In addition, a recent report described reversible elevations in serum creatinine levels in 24 hypothyroid patients studied before radioiodide imaging for thyroid carcinoma (4); some patients ...References1. Hussein WI, Green R, Jacobsen DW, Faiman C. Normalization of hyperhomocysteinemia with l-thyroxine in hypothyroidism. Ann Intern Med. 1999;131:348-51. LinkGoogle Scholar2. Bradley SE, Stephan F, Coelho JB, Reville P. The thyroid and the kidney. Kidney Int. 1974;6:346-65. CrossrefMedlineGoogle Scholar3. Montenegro J, Gonzalez O, Saracho R, Aguirre R, Gonzalez O, Martinez I. Changes in renal function in primary hypothyroidism. Am J Kidney Dis. 1996;27:195-8. CrossrefMedlineGoogle Scholar4. Kreisman SH, Hennessy JV. Consistent reversible elevations of serum creatinine levels in severe hypothyroidism. Arch Intern Med. 1999;159:79-82. CrossrefMedlineGoogle Scholar5. Arnadottir M, Hultberg B, Nilsson-Ehle P, Thysell H. The effect of reduced glomerular filtration rate on plasma total homocysteine concentration. Scand J Clin Lab Invest. 1996;56:416-6. CrossrefGoogle Scholar Author, Article, and Disclosure InformationAuthors: Daniel Weiss, MDAffiliations: Case Western Reserve University School of Medicine; Cleveland, OH 44106 (Weiss) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoNormalization of Hyperhomocysteinemia with l-thyroxine in Hypothyroidism Wiam I. Hussein , Ralph Green , Donald W. Jacobsen , and Charles Faiman Hyperhomocysteinemia in Hypothyroidism Charles Faiman , Donald W. Jacobsen , and Ralph Green Metrics 18 April 2000Volume 132, Issue 8Page: 677KeywordsBlood plasmaCreatinineGlomerular filtration rateHyperthyroidismHypothyroidismThyroid carcinoma ePublished: 15 August 2000 Issue Published: 18 April 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 1954: RNA-binding protein Musashi1 activates STAT3 signaling via PKR phosphorylation and promotes tumorigenicity of glioblastoma cells
Authors: Hsiao-yun Chen, Shih-Hwa Chiou
Journal: Cancer Research (2014)

Abstract Glioblastoma multiforme (GBM) is one of the deadly malignant brain tumors for human. GBM is easily recurrent and resistant to the clinical approaches. Those clinical interventions are considered a minor stress, therefore, promotes tumorigenicity of cancer cells. RNA-binding protein, Musashi-1 (Msi-1), is highly expressed in the central nervous system and it is known to act a vital role in regulation of neuron cell development. Moreover, Msi-1 is elevated in several cancer tissues and confirmed as a positive regulator in cancer progression. In this present article, we hypothesized that Msi-1 promotes cell tumorigenicity and enhances drug resistance under expose to stress condition in human GBM cells. We validated over expression of Msi-1 lead a protective effect in mitigating drug-induced cells death. Under stress stimulation, overexpression of Msi-1 triggers Msi-1-granules generation, stress granules (SGs) markers such as p-PKR, p-PERK and p-eIF2-α phosphorylation. The activated-PKR contributes down-stream leading to enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3, thereby enhancing tumorigenicity in GBM cells. Knocking down of Msi-1 and PKR obviously antagonist those finding, inhibitors of PKR and STAT3 reduced cells viability under expose to stress condition. Our findings concluded that Msi-1 contributes a positive role in regulation of tumorigenicity and drug resistance to GBM cells under stress condition by modulating PKR/STAT3 mechanism. Citation Format: Hsiao-yun Chen, Shih-Hwa Chiou. RNA-binding protein Musashi1 activates STAT3 signaling via PKR phosphorylation and promotes tumorigenicity of glioblastoma cells. [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 1954. doi:10.1158/1538-7445.AM2014-1954
Low serum testosterone as an indicator of metastatic bronchial carcinoma.
Authors: J Moore-Gillon
Journal: Thorax (1988)

Effect of particle size of bronchodilator aerosols on lung distribution and pulmonary function in patients with chronic asthma SIR,-We feel that we must comment on the recent paper by Dr DM Mitchell and others (June 1987;42:457-61), since its findings are likely to be misinterpreted by many readers.Dr Mitchell and his colleagues nebulised salbutamol as aerosols of particles with mass median aerodynamic diameters (MMADs) of 1 4 and 5 5 jim in eight patients with chronic and severe stable asthma.On the basis of their data from previous radioaerosol deposition studies, they set out deliberately to deliver the same amount of drug to the lungs for each of the two aerosols, and found no difference in bronchodilator response.Although their methods were sound and their paper is of scientific interest, the study bears little relation to the clinical circumstances in which a fixed dose is placed in whatever nebuliser comes to hand and then nebulised "to dryness."Nebulisers differ widely in their droplet MMADs-from I to 12 jim-and hence in the amounts of drug able to penetrate the oropharynx and reach the lungs.We have compared two commonly used nebulisers, producing particles with an MMAD of 3 3 and 7 7 jm respectively: almost three times more radioaerosol was deposited in the lungs with the smaller aerosol and in a cumulative dose-response study using salbutamol bronchodilatation was significantly greater.'The use of the CIS-Optimist system seems a curious choice of nebuliser as this unit was designed to produce fine aerosols for ventilation scanning and achieves this by filtering out a very high proportion of the dose before it gets to the patient.Thus it would not be an ideal system for bronchodilator
Is the Smoking Decision an 'Informed Choice'?
Authors: Howard Leventhal
Journal: JAMA (1987)

The argument that people freely choose to smoke assumes that individuals at the point of initiation of smoking (often in adolescence) hold accurate beliefs about smoking. Smoking beliefs and the presence of known smoking risk factors were assessed in interviews with a sample of 895 urban young people. The respondents greatly overestimated the prevalence of adult and peer smoking, negative attitudes of their peers were greatly underestimated, a large proportion believed that they would be less likely than other people to contract a smoking-related illness if they became smokers, and there was a general lack of understanding of the adverse consequences experienced upon smoking cessation. These misperceptions were more common among youngsters who were smokers, who intended to smoke, or who had friends or family members who smoked. Because misinformation among young people is widespread and those at greatest risk for smoking are the most misinformed, the tobacco industry's argument that the decision to smoke reflects an "informed choice" is without merit. (<i>JAMA</i>1987;257:3373-3376)
Acute Parathyroid Hormone Response to Epinephrine In Vivo
Authors: Jan A. Fischer, Jürg W. Blum, Ulrich Binswanger
Journal: Journal of Clinical Investigation (1973)

The acute effects of epinephrine, norepinephrine, and isoproterenol on the plasma immunoreactive parathyroid hormone (iPTH) response were studied in 13 550-600 kg cows. Catecholamines were infused for 7.0 min. During epinephrine infusions at 0.08 mumol/min iPTH increased from 0.48+/-0.12 (mean+/-SE, ng/ml) to 1.09+/-0.18 ng/ml (P < 0.02). Small increases in plasma free fatty acids and glucose could be detected with 0.08 mumol/min epinephrine; the iPTH response to epinephrine was as sensitive as the free fatty acid and glucose responses and possibly of physiological importance. Plasma calcium (total and ionized) and magnesium did not change. The responses were more pronounced at 0.8 mumol/min epinephrine with a mean iPTH increase from 0.49+/-0.16 ng/ml to 1.74+/-0.35 ng/ml (P < 0.01). Small decreases in plasma calcium occurred at 0.8 mumol/min epinephrine, but the plasma magnesium remained unchanged. However, when the plasma calcium was lowered with ethylene glycol bis(beta-aminoethyl ether)-N, N'-tetraacetic acid (EGTA), a much more pronounced lowering of the plasma calcium was required to produce comparable increases of the plasma iPTH concentrations than when epinephrine was infused. It appears that epinephrine has a direct effect on the release of iPTH from the parathyroid glands. Simultaneous infusions of calcium and epinephrine suppressed the stimulation by epinephrine. This points towards a common mechanism of the regulation of parathyroid hormone secretion caused by decreases in the extracellular calcium concentration and/or alterations in the distribution of calcium within parathyroid cells following the administration of epinephrine. The iPTH response to epinephrine was suppressed in the presence of propranolol. Isoproterenol was less active in raising iPTH than epinephrine, and norepinephrine was the least active. The stimulation by isoproterenol and the suppression by propranolol suggest beta adrenergic receptor sites within the parathyroid glands.