tbuckley/cabot-search huggingface dataset:
O4.06 * ANALYSIS OF RAF PROTEINS IN MALIGNANT GLIOMAS
Authors: C. Hagemann, J. Gloger, A. F. Kessler, T. Linsenmann, G. H. Vince, R. Ernestus, M. Lohr
Journal: Neuro-Oncology (2014)

OBJECTIVE: Low grade astrocytoma WHO grade II (LGA) display an increased expression of the platelet-derived growth factor receptor. The epidermal growth factor receptor is overexpressed in 60% of glioblastoma multiforme (GBM) and amplified in 40%. Both of these tyrosine kinase receptors signal to the mitogen activated Ras-RAF-MEK-ERK signaling pathway. RAF proteins are well known oncogenes, comprised by a family of three members: A-RAF, B-RAF and C-RAF. Especially B-RAF has been defined to be mutationally activated in a high percentage of melanomas, ovarial, thyroidal and colon carcinomas. C-RAF is discussed to be involved in lung cancer development. However, the role of Raf proteins during development of astrocytic tumors has only rarely been addressed in the literature. METHODS: The mutational status of A-RAF and B-RAF was assessed by sequencing in 66 and 44 human GBM, respectively. A panel of three normal brain samples, 15 LGA and 15 GBM was analyzed for gene amplification by dot blot hybridization, for mRNA expression by semiquantitative RT-PCR and for protein expression by Western blotting. The results were correlated with patients' prognosis. Finally, we performed functional assays using transient overexpression and siRNA mediated knock-down to address a putative function of A-RAF in glioma cell proliferation and migration. RESULTS: RAF mutations are rare events in GBM. No mutations were found in the A-RAF gene and only 2% of the tumors contained activating B-RAF mutations. A-RAF gene amplification could be detected more often. However, all three Raf proteins were overexpressed in astrocytic tumors. Both, A-RAF and C-RAF expression was negatively correlated with the patients' survival. In contrast, B-RAF expression had a positive effect. Neither A-RAF, nor C-RAF had any influence on proliferation or migration of GBM cells in functional assays. There are hints for an involvement of A-RAF in the regulation of the tumor cells metabolism and of C-RAF in angiogenesis. CONCLUSION: Raf proteins are clearly overexpressed in GBM and play a role during progression of these tumors. Therefore, the RAF-isoforms are possible candidates for small molecule therapies in conjunction with targeting parallel signaling cascades. However, initially specific functions of RAF during tumorigenesis of human gliomas have to be elucidated.
Compassion's Way: A Doctor's Quest Into the Soul of Medicine
Authors: J. M. Clark
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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
Tissue Burdens of Toxic Pollutants
Authors: Dean W. Roberts
Journal: JAMA (1982)

An article in this issue ofThe Journal(p 2112) presents new information on the tissue burden of polybrominated biphenyls (PBBs) of Michigan residents and relates this to the tissue burdens of polychlorinated biphenyls (PCBs) and 2,2′-<i>bis</i>-(<i>p</i>-chlorophenyl)-1,1-dichloroethylene (DDE), a metabolite of dichlorodiphenyl trichloroethane (DDT). The finding that 70% of a random sample of the population have detectable levels of PBB in serum and 9796 have PBB in adipose tissue is a dramatic one. It is another reminder of our vulnerability to the increasing number and volume of potentially toxic chemicals used in manufacturing, agriculture, pest control, and food processing. The concomitant tissue burdens of PCB, PBB, and DDE may have greater biologic significance than each considered separately. The nature and extent of environmental contamination by the three chemicals vary greatly. The oldest is PCB, which was introduced in the United States in 1930. Its use in manufacturing
Target selection, attention, and the superior colliculus
Authors: Richard J. Krauzlis
Journal: Behavioral and Brain Sciences (2007)

Consistent with the target article, recent evidence indicates that the superior colliculus (SC) is somehow involved in target selection. However, it is not yet known whether this function is inherent to the SC or inherited from its inputs, how the selection process occurs for different movements, or how target selection by the SC is related to covert selection (i.e., attention).
Saturated fat–rich diet enhances selective uptake of LDL cholesteryl esters in the arterial wall
Authors: Toru Seo, Kemin Qi, Chuchun Chang, Ying Liu, Tilla S. Worgall, Rajasekhar Ramakrishnan, Richard J. Deckelbaum
Journal: Journal of Clinical Investigation (2005)

Plasma LDL levels and atherosclerosis both increase on a saturated fat-rich (SAT) diet. LDL cholesterol delivery to tissue may occur via uptake of the LDL particles or via selective uptake (SU), wherein cholesteryl ester (CE) enters cells without concomitant whole-particle uptake. It is not known how dietary fats might directly affect arterial LDL-CE uptake and whether SU is involved. Thus, mice that are relatively atherosclerosis resistant (C57BL/6) or susceptible to atherosclerosis (apoE) were fed a chow or SAT diet and injected with double radiolabeled or fluorescent-labeled human LDL to independently trace LDL-CE core and whole-particle uptake, respectively. Our results show that a SAT diet increased contributions of SU to total arterial LDL-CE delivery in C57BL/6 and apoE mice. The SAT diet increased plasma fatty acid and cholesterol levels; cholesterol, but not fatty acid, levels correlated with SU, as did the degree of atherosclerosis. Increased SU did not correlate with arterial scavenger receptor class B type I levels but paralleled increased lipoprotein lipase (LPL) levels and LPL distribution in the arterial wall. These studies suggest that arterial LDL-CE delivery via SU can be an important mechanism in vivo and that dietary influences on arterial LPL levels and atherogenesis modulate arterial LDL-CE delivery, cholesterol deposition, and SU.
Structure, Immunology, and Cell Reactivity of Low Density Lipoprotein from Umbilical Vein of a Newborn Type II Homozygote
Authors: Wolfgang Patsch, Joseph L. Witztum, Richard Ostlund, Gustav Schonfeld
Journal: Journal of Clinical Investigation (1980)

In this report we compare the cord blood lipoproteins of a newborn boy homozygote who has low density lipoprotein (LDL) receptor-defective familial hypercholesterolemia (FH) with the lipoproteins from cord blood of normal newborns. Plasma LDL-cholesterol and apoprotein (Apo)B were 612 and 233 mg/dl (vs. 31±16 and 24±12 mg/dl, respectively, for normals, n = 21). LDL-cholesterol/ApoB ratio was 2.6 vs. 1.4±0.5. Levels of ApoA-I, ApoA-II, and HDL-cholesterol were similar to normal cord plasma. Thus, the lipoprotein abnormality is apparent at birth and is definitely present in LDL. Abnormalities in other lipoprotein, lipid, and in plasma apoprotein levels were not detected. On zonal ultracentrifugation, FH LDL was comprised of two populations (LDLa and LDLb), both faster floating than normal cord LDL (LDLc). This difference was due to the larger diameters of the particles on electron microscopy (LDLa = 276Å±32 and LDLb = 260Å±38 vs. LDLc = 237Å±26, n = 200 each, mean±1 SD), and their higher contents of lipids relative to protein (86 and 82% vs. 74%, LDLa, LDLb, and LDLc, respectively). More than 94% of the protein in both the FH and the normal preparations consisted of ApoB. FH LDL were more effective than control LDL in competing with 125I-LDL (adult) for limiting amounts of anti-LDL antibodies in radioimmunoassay. FH LDL also competed more effectively for binding to LDL receptors on cultured fibroblasts at 4°C, and FH LDL also delivered more cholesterol into the cells. Cells grown in lipoprotein-deficient serum contained 44±2 μg cholesterol/mg cell protein, incubation of cells for 18 h at 37°C in 5 μg/ml FH LDL (protein) or in normal LDL raised cellular cholesterol levels to 75±2 and 60±2 μg/mg, respectively.
Isolation of Poliovirus — John Enders and the Nobel Prize
Authors: Fred S. Rosen
Journal: New England Journal of Medicine (2004)

When John Enders was informed, 50 years ago this month, that he was the sole recipient of the Nobel Prize in Medicine or Physiology for 1954, he declined the honor. He wrote to the Swedish authorities that he would accept the prize only if it could be shared with "those who did the work." It was agreed that Thomas Weller and Frederick Robbins would be corecipients with Enders. This act, one of the most gracious in the history of the Nobel Prize, reveals the profound decency and modesty of John Enders.John Franklin Enders was a Connecticut Yankee, born into . . .
Updating UK estimates of age, sex and period specific cumulative constant tar cigarette consumption per adult
Authors: B. A Forey, P. N Lee, J. S Fry
Journal: Thorax (1998)

In 1993 we presented age and sex specific estimates of cumulative constant tar cigarette consumption (CCTCC) per adult for five year periods to 1986-90. These were derived from annual surveys conducted for the Tobacco Manufacturers' Association (TMA) since 1946, extrapolated back to 1891 for men and to 1921 for women and corrected for the decline in average (machine smoked) tar levels. We now provide estimates for 1991-5.TMA surveys having ceased, 1991-5 estimates of manufactured cigarette consumption per adult (MCA) were derived from the General Household Survey (GHS) and corrected for the continuing decline in tar. These estimates were divided by 0.75 (men) and 0.80 (women), based on a comparison of GHS and TMA data for 1971-90, to allow accumulation with the TMA derived estimates prior to 1991.For both sexes the GHS/TMA ratio of MCA varied little by age or five year period, justifying the use of the correction factors when adjusting GHS estimates for 1991-95. TMA estimates were higher than GHS estimates as only TMA sales-corrected their data for understatement of smoking and the surveys differed in questions on handrolled cigarette smoking. The 1991-95 data confirm the continuing decline in CCTCC at all ages in men. Women show a less steep decline for ages 30-64 and an increase for ages 65-84.The GHS data can validly be used to update the CCTCC estimates. Some reservations about the use of CCTCC are discussed.
Atlas of Orthopaedic Surgery
Authors: V. T. WORRALL
Journal: JAMA (1974)

This two-volume text provides a clear illustrative guide to the operative encounter with the musculoskeletal system. To present their material, Drs. Goldstein and Dickerson have relied heavily on more than 1,500 simplified illustrations and a concise accompanying narrative. The chapters, arranged by anatomical regions, cover most of the more frequently employed operative procedures particular to each region. Little in the way of background or preoperative discussion is available, but a rather complete reference section follows each chapter. The final chapter deals with special techniques of interest to the orthopedic surgeon. Operative descriptions and illustrations describe the methods of tendon, artery, and nerve repair as well as arthroscopy and muscle biopsy. The reader should find these volumes easy to use. The illustrations are not overly detailed, the narrative is clear and concise, and most important, the illustrations appear on the page opposite the accompanying narrative, thus providing easy reference. To compile
Abstract 2123: Her2 affects AR phosphorylation at serine 81 and suppresses cell proliferation of breast cancer cell line MDA-MB-453
Authors: Pao-Hsuan Huang, Chen-Chuan Huang, Yueh-Tsung Lee, Chia-Herng Yue, Ho Lin
Journal: Cancer Research (2014)

Abstract Breast cancer is a hormone-related carcinoma and the most commonly diagnosed malignancy among women. Although human epidermal growth factor receptor-2 (Her2), estrogen receptor (ER), and progesterone receptor (PR) are the major diagnostic markers and therapeutic targets to breast cancer, searching for additional molecular targets becomes an important issue and one of the candidates is androgen receptor (AR). In recent studies, AR expresses in 70% breast cancer cases and its expression connects to low recurrence and high survival rate. Our previous study shows that S81 phosphorylation is critical for AR protein stability and modulated by Her2 in prostate cancer cells. In this study, we explore the roles of AR and Her2 in proliferation of breast cancer cell line, MDA-MB-453. The data show that AR which was activated by synthetic androgen R1881 decreased proliferation of MDA-MB-453 cells. AR knockdown increased both phosphorylation of Akt and ERK. Notably, AR activation decreased protein level of Early growth response 1 (Egr1) and increased protein level of cyclin-dependent kinase inhibitor p27, which suggests the correlation of AR activation and proliferation suppression. Besides, Her2 activation by Heregulin (HRG) decreased the levels of p-S81-AR. Her2 inhibition by small molecular inhibitor, Lapatinib, increased the levels of p-S81-AR and p27. In summary, our results indicate that Her2 might negatively regulate AR activation and contribute to suppressive proliferation of MDA-MB 453 cells. Citation Format: Pao-Hsuan Huang, Chen-Chuan Huang, Yueh-Tsung Lee, Chia-Herng Yue, Ho Lin. Her2 affects AR phosphorylation at serine 81 and suppresses cell proliferation of breast cancer cell line MDA-MB-453. [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 2123. doi:10.1158/1538-7445.AM2014-2123
FEASIBILITY OF ROUTINE CYP2C19 GENOTYPING AND PLATELET FUNCTION TESTING IN PATIENTS UNDERGOING ELECTIVE CORONARY STENTING IN A HIGH-VOLUME CARDIAC CATHETERIZATION LAB
Authors: Joseph Sweeny, Stuart Scott, David Zhang, Robert Desnick, Samin Sharma, Erwin Bottinger
Journal: Journal of the American College of Cardiology (2012)
Foam Cell Formation Inhibits Growth of <i> <b>Chlamydia pneumoniae</b> </i> but Does Not Attenuate <i> <b>Chlamydia pneumoniae</b> </i> –Induced Secretion of Proinflammatory Cytokines
Authors: Erwin Blessing, Cho-chou Kuo, Tsun-Mei Lin, Lee Ann Campbell, Florian Bea, Brian Chesebro, Michael E. Rosenfeld
Journal: Circulation (2002)

Background — It has not yet been determined whether lipid-loaded macrophages (foam cells), a major cellular component of atherosclerotic lesions, have the capacity to support growth of Chlamydia pneumoniae and be activated to secrete proinflammatory cytokines in response to C pneumoniae infection. Methods and Results — Lipid loading of RAW 264.7 cells and mouse peritoneal macrophages with either oxidized or acetylated LDL significantly inhibits the growth of C pneumoniae. Modified forms of LDL are not directly toxic to C pneumoniae and do not inhibit either the initial binding or internalization of C pneumoniae by macrophages. Lipid loading does not reduce infection of macrophages with Chlamydia trachomatis . Treatment of lipid-loaded macrophages with live, heat-killed, or UV-inactivated C pneumoniae stimulates secretion of cytokines. C pneumoniae also induces expression of the mRNA for tumor necrosis factor-α in foam cells despite inhibition of nuclear factor-κB binding to DNA by prior treatment with oxidized LDL. Conclusions — Foam cell formation is not conducive to growth of C pneumoniae but does not inhibit the C pneumoniae –induced secretion of proinflammatory cytokines.
Complication Rates Among Cancer Patients With Peripherally Inserted Central Catheters
Authors: Louise J. Walshe, Sharp F. Malak, Janet Eagan, Kent A. Sepkowitz
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Peripherally inserted central catheters (PICCs) are frequently used to deliver outpatient courses of intravenous therapy. However, the rates and risks of complication for this device have not been well-studied. Our objective was to determine the incidence and risk factors of PICC-related complications with a 1-year prospective observational study. PATIENTS AND METHODS: All PICCs inserted in adult and pediatric patients at Memorial Sloan-Kettering Cancer Center (MSKCC) were followed prospectively. The device insertion team, inpatient nurses, and various home-care companies and outside institutions collected longitudinal data. RESULTS: Three hundred fifty-one PICCs were inserted during the study period and followed for a total of 10,562 catheter-days (median placement, 15 days; range, 1 to 487 days). Two hundred five PICCs (58%) were managed by home-care companies and outside institutions, and 146 PICCs (42%) were managed exclusively at MSKCC. For these 205 PICCs, 131 nurses from 74 home-care companies and institutions were contacted for follow-up clinical information. In all, 115 (32.8%) of 351 PICCs were removed as a result of a complication, for a rate of 10.9 per 1,000 catheter-days. Patients with hematologic malignancy or bone marrow transplant were more likely to develop a complication, whereas those with metastatic disease were less likely. CONCLUSION: Complications occur frequently among cancer patients with PICCs, and long-term follow-up is onerous. Despite a high complication rate, the ease of insertion and removal argues for continued PICC use in the cancer population.
Response to Letter Regarding Article, “Ablation of Matrix Metalloproteinase-9 Increases Severity of Viral Myocarditis in Mice”
Authors: David Marchant, Caroline Cheung, Elizabeth K.Y. Walker, Honglin Luo, Zongshu Luo, Jingchun Zhang, Bobby Yanagawa, Maziar Rahmani, Bruce M. McManus, Jennifer Cox, Christopher Overall, Robert M. Senior
Journal: Circulation (2008)
Joseph Hodgson Briggs
Authors: C. Parks
Journal: BMJ (2002)

Former consulting physician London (b Workington 1928; q St Bartholomew's Hospital 1951; MRCP 1958), d 22 January 2002.

In 1967 he gained a degree of not unwelcome notoriety when he became the second chairman of the newly launched Junior Hospital Doctors Association (JHDA). The JHDA was one of several organisations of the time that started by challenging the BMA's right to be the sole negotiating body for doctors. In those days the BMA's own Hospital Junior Staffs Committee was little more than a talking shop adjunct to the Central Consultants and Specialists Committee. At the same time, under the slogan “no taxation without proper representation,” the JHDA challenged the General Medical Council to withdraw its imposition of a new annual retention fee or to become more democratic of the profession at large. It also began the debate over the morality of junior doctors having to work more than 100 hours a week.
Pulmonary toxicity of malaria prophylaxis.
Authors: A. C. Davidson, C. Bateman, C. Shovlin, M. Marrinan, G. H. Burton, I. R. Cameron
Journal: BMJ (1988)

4 observations de pneumopathie eosinophile chez des sujets suivant un traitement prophylactique, 3 avec pyrimethamine-dapsone, 1 avec pyrimethamine-chloroquine
FDG PET Images in a Patient With Erdheim-Chester Disease
Authors: Chrissa Sioka, Juvianee Estrada-Veras, Irinia Maric, William A. Gahl, Clara C. Chen
Journal: Clinical Nuclear Medicine (2013)

Erdheim-Chester disease is an uncommon non-Langerhans-cell histiocytosis, due to excessive production of histiocytes deposited in various organs and tissues in the human body. FDG PET was performed in a 68-year-old man with documented active Erdheim-Chester disease to evaluate the extent of the disease. The patient was previously treated with high-dose subcutaneous Interferon α2b, 1,000,000 units 3 times a week, but treatment was interrupted approximately 5 weeks before evaluation at the National Institutes of Health because of adverse effects of the medication. FDG PET/CT showed lesions were imaged in brain, heart, mediastinum, abdomen, and skeleton.
Possible Tobramycin Delirium-Reply
Authors: Cheryl F. McCartney
Journal: JAMA (1982)

<h3>In Reply.—</h3> We agree with Dr Hamilton that the isolation of an etiologic factor in an adverse clinical event is complex. We submit that although there were possible "contributing" factors<sup>1,2</sup>of age and infection, in this patient, these do not qualify as alternate "etiologic"<sup>1,2</sup>candidates. The patient had never been delirious before this reported episode despite her age, five previous urinary tract infections in the three years before admission, ongoing antibiotic treatment, and surgical procedures. Although it is true that CNS depressant medications themselves can cause delirium, our patient had had extensive experience with them without adverse effects. We should clarify that her clinic record shows repeated prescriptions during several years (up to and including her outpatient visit two weeks before admission) of CNS depressants on an "as-needed" basis. These were APC with codeine (60 mg), diazepam (5 mg), and ethchlorvynol (750 mg). We did not mention these