tbuckley/cabot-search huggingface dataset:
Abstract 2276: Coordinate autophagy and PI3K/Akt/mTOR pathway inhibition enhances cell death in melanoma
Authors: Xiaoqi Xie, Janice M. Mehnert, Eileen P. White
Journal: Cancer Research (2012)

Abstract The PI3K/Akt/mTOR pathway is a critical survival pathway in numerous malignancies, including melanoma. Inhibitors of this pathway in cancer cells, in particular mTOR, are commonly cytostatic rather that cytotoxic, which may potentially limit efficacy of these agents. mTOR inhibition also induces the survival pathway of autophagy, a catabolic process whereby cells collect and recycle cellular components to sustain energy homeostasis. Thus we tested the hypothesis that autophagy induction by mTOR inhibitors directly limited their efficacy for the treatment of melanoma. Here we found that melanoma exhibits high basal levels of autophagy, as evidenced by a) detection of autophagosomes using LC3 fluorescence and autophagic flux in multiple melanoma cell lines and b) increased LC3 fluorescence in human primary and metastatic melanomas compared to benign nevi. Knockdown of Atg7, a key element of autophagy machinery, resulted in cell death, indicating that survival of melanoma cells is autophagy dependent. We also showed that the autophagy inhibitor hydroxychloroquine (HCQ) shows synergy when combined with the mTOR inhibitor CCI-779 (temsirolimus), inducing cell death via increased apoptosis in melanoma cell lines and in 3-D spheroid cell cultures. Since autophagy eliminates mitochondria that are a source of toxic reactive oxygen species (ROS) and mediators of apoptosis, we tested the possibility that this contributed to melanoma survival. To test this potential mechanism, we examined the role of the transcription factor Nrf2, a master regulator of antioxidant defense. Treatment with CCI-779 inactivated Nrf2 by blocking its nuclear translocation and creating the requirement for autophagy to eliminate ROS-producing mitochondria. Combination treatment with CCI-779 and HCQ then prevented mitochondrial elimination by autophagy, resulting in increased ROS production compared to either agent alone and increased cell death. Conversely, knockdown of the Nrf2 binding protein and inhibitor Keap1 increased Nrf2 activity, resulting in increased cell culture survival and resistance to treatment with CCI-779 and HCQ. These data suggest that coordinate inhibition of the PI3K/Akt/mTOR and autophagy pathways promotes ROS-mediated apoptosis and is a new therapeutic paradigm for the treatment of melanoma. 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 2276. doi:1538-7445.AM2012-2276
Effects of Environmental Temperature upon Capillary Resistance in Patients with Rheumatoid Arthritis and Other Individuals
Authors: J. L. Potter, J. J. R. Duthie
Journal: Annals of the Rheumatic Diseases (1961)

In two previous surveys of capillary resistance (C.R.) it was found that the mean resistance in groups of patients with rheumatoid arthritis was significantly lower than in groups with other diseases (Potter and Wigzell, 1957).In these surveys the inter-subject variation of C.R. was substantial, even after allowance was made for the systematic influence of age, sex, and disease.The data consisted of the results of one test per individual and therefore provided no information on the nature of the residual variation.This presumably included genuine inter- and intra-subject variation, together with variation due to experimental error.As with other methods for measuring C.R., the negative pressure tests used in these surveys cannot be repeated in a given area of skin at intervals of less than 24 hours, hence * Cortisone orally 50.100 mg. per 24 hrs, or Prednisolone orally 5-20 mg. per 24 hrs 144
Self-monitoring of blood glucose: language and financial barriers in a managed care population with diabetes.
Authors: A J Karter, A Ferrara, J A Darbinian, L M Ackerson, J V Selby
Journal: Diabetes Care (2000)

OBJECTIVE: Self-monitoring of blood glucose (SMBG) is a cornerstone of diabetes care, but little is known about barriers to this self-care practice. RESEARCH DESIGN AND METHODS: This cross-sectional study examines SMBG practice patterns and barriers in 44,181 adults with pharmacologically treated diabetes from the Kaiser Permanente Northern California Region who responded to a health survey (83% response rate). The primary outcome is self-reported frequency of SMBG. RESULTS: Although most patients reported some level of SMBG monitoring, 60% of those with type 1 diabetes and 67% of those with type 2 diabetes reported practicing SMBG less frequently than recommended by the American Diabetes Association (three to four times daily for type 1 diabetes, and once daily for type 2 diabetes treated pharmacologically). Significant independent predictors of nonadherent practice of SMBG included longer time since diagnosis, less intensive therapy, male sex, age, belonging to an ethnic minority, having a lower education and neighborhood income, difficulty communicating in English, higher out-of-pocket costs for glucometer strips (especially for subjects with lower incomes), smoking, and excessive alcohol consumption. CONCLUSIONS: Considerable gaps persist between actual and recommended SMBG practices in this large managed care organization. A somewhat reduced SMBG frequency in subjects with linguistic barriers, some ethnic minorities, and subjects with lower education levels suggests the potential for targeted, culturally sensitive, multilingual health education. The somewhat lower frequency of SMBG among subjects paying higher out-of-pocket expenditures for strips suggests that removal of financial barriers by providing more comprehensive coverage for these costs may enhance adherence to recommendations for SMBG.
LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system
Authors: Lijuan Zhao, Yuko Ohtaki, Kouji Yamaguchi, Misao Matsushita, Teizo Fujita, Takashi Yokochi, Haruhiko Takada, Yasuo Endo
Journal: Blood (2002)
Abstract 2983: Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation
Authors: Tiziana Bruno, Agata De Santis, Gianluca Bossi, Silvia Di Agostino, Cristina Sorino, Francesca De Nicola, Simona Iezzi, Annapaola Franchitto, Barbara Benassi, Aristide Floridi, Alfonso Bellacosa, Claudio Passananti, Giovanni Blandino, Maurizio Fanciulli
Journal: Cancer Research (2010)

Abstract Che-1 is a RNA polymerase II binding protein involved in the regulation of gene transcription, and in response to DNA damage promotes p53 transcription. In this study, we investigated whether Che-1 regulates mutant p53 expression. We found that Che-1 is required for sustaining mutant p53 expression in several cancer cell lines, and Che-1 depletion by siRNA induces apoptosis both in vitro and in vivo. Notably, loss of Che-1 activates DNA damage checkpoint response and induces transactivation of p73. Therefore, these findings suggest a new therapeutic approach that allowing simultaneous modulation of p73 and mutant p53 levels might be used to target the large fraction of human tumors harboring p53 mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2983.
William Charles Wells
Authors: Anderson Nettleship
Journal: New England Journal of Medicine (1956)

SIR William Osler's respect for the Anglo-American, William Charles Wells, led him to refer to Wells as "that remarkable philosopher and physician, Wells of Charleston." Re-examination of Wells's life and work emphasizes how truly significant this man was. It is no longer important to argue which is most important in his life and work: his nationality (American), his training (Scotch-English) or his sympathies (Loyalist), or where he lived. He was a fine example of the new, vigorous, first-generation immigrant who caught the medical and cultural fires of these shores and carried them back to the Old World to become productive . . .
BIFURCATION ANGLE AND T-STENTING AND SMALL PROTRUSION (TAP) BIFURCATION PERCUTANEOUS CORONARY INTERVENTION TECHNIQUE
Authors: Young Bin Song, Joo-Yong Hahn, Jin-Ho Choi, Seung-Hyuk Choi, Sang Hoon Lee, Hyeon-Cheol Gwon
Journal: Journal of the American College of Cardiology (2010)
WHO processes on dealing with a pandemic need to be overhauled and made more transparent
Authors: J. Zarocostas
Journal: BMJ (2011)

A1 Geneva

The World Health Organization failed to manage possible conflicts of interests between its expert advisers and industry in handling the H1N1 flu pandemic, an independent review panel has found.

The review, chaired by Harvey Fineberg, president of the US Institute of Medicine, concluded procedures were inadequate, should be overhauled, and made more transparent.

The panel found no evidence of “attempted or actual influence” by commercial interests on advice or decisions taken by the WHO concerning the pandemic. But WHO failed to acknowledge legitimate reasons for some criticism, in particular, inconsistent descriptions of a pandemic that “may have inadvertently contributed to confusion and suspicion.”

An investigation published last year by the BMJ and the Bureau of Investigative Journalism ( BMJ 2010;340:c2912, doi:10.1136/bmj.c2912) found that key scientists advising the WHO on planning for an influenza …
Inhibitory effect of secretin and cholecystokinin on Heidenhain pouch responses to gastrin extract and histamine
Authors: I. E. Gillespie, M. I. Grossman
Journal: Gut (1964)

Rapid intravenous injections of secretin and cholecystokinin (Vitrum) inhibited the acid response of Heidenhain pouch dogs to continuous intravenous gastrin extract. Cholecystokinin caused greater inhibition than secretin. Responses to small doses of histamine were inhibited by cholecystokinin but not by secretin.
Long-term angiographic and clinical outcome after implantation of a ballon-expandable stent in the native coronary circulation
Authors: Michael P. Savage, David L. Fischman, Richard A. Schatz, Paul S. Teirstein, Martin B. Leon, Donald Baim, Stephen G. Ellis, Eric J. Topol, John W. Hirshfeld, Michael W. Cleman, Maurice Buchbinder, Steven Bailey, Richard Heuser, Craig M. Walker, R.Charles Curry, Sharon Gebhardt, Randal Rake, Sheldon Goldberg
Journal: Journal of the American College of Cardiology (1994)

Objectives. The purpose of this study was to examine the long-term clinical and angiographic outcome after coronary implantation. Background. Previous reports haw shown a discordance between the excellent initial angiographic results and subsequent adverse clinical events after coronary artery stenting. Methods. Single Palmaz-Schatz stents were electively implanted in the native coronary arteries of 300 consecutive patients. Angiograms were obtained at baseline, after balloon angioplasty, after stent implantation and at 6 months after implantation. Films were analyzed by a panel of engiographers utilizing en automated edge detection program, Clinical events, including death, myocardial infarction, coronary bypass surgery and repeat angioplasty, were recorded for 1 year. Results. Although there were no acute in-laboratory vessel closures, stent thrombosis occurred in 14 patients (4.7%) at a mean ±SD of 5 ± 3 days after implantation. Two hundred fifty-eight (90%) of 286 eligible patients had follow-up angiography at 6.1 ± 2.2 months after stent implantation. Minimal lumen diameter increased from 0.80 ± 039 mm at baseline to 1.65 +- 0.51 mm after angioplasty and further increased to 2.55 ± 0.49 mm after stent placement (p = 0.0001). At follow-up there was a 0.85-mm late loss in lumen diameter, with a final minimal lumen diameter at 6 months of 1.70 ± 0.71 mm. Restenosis, defined as ≥ 50% diameter stenosis at follow-up, occurred in 14% of patients with previously untreated lesions and in 39% of patients with previous angioplasty (p < 0.001). Clinical events after 1 year for the entire group of 300 patients included death in 0.7%, myocardial infarction in 3.7%, bypass grafting in 8% and repeat angioplasty in 13%. Freedom from any adverse clinical event was 80% for all treated patients and 87% for those with previously untreated lesions. Conclusions. Elective use of this balloon-expandable stent in the native coronary circulation is associated with a low restenosis rate by quantitative angiography in previously untreated lesions and a favorable clinical outcome with an excellent event-free survival rate at 1 year.
US scientists protest cuts to research funding that aim to reduce national deficit
Authors: J. H. Tanne
Journal: BMJ (2012)

Major US universities and science organizations have criticized automatic federal spending cuts being introduced as a result of “sequestration,” which will take place on 1 January 2013 unless Congress takes action.

The budget cuts, and the tax increases that accompany them, are often called the “the fiscal cliff” and result from laws enacted during the administration of President George W Bush to reduce the budget deficit.

The Association of American Universities, the Association of Public and Land-Grant Universities, …
The Evolution of Population Science
Authors: J. Michael Gaziano
Journal: JAMA (2010)

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
Perceptions of pain relief after surgery
Authors: S Robinson, I Windram, D Fell
Journal: BMJ (1990)

The purpose of this study was to determine the nature of the CD4<sup>+</sup> Th cell responses induced after nasal-pulmonary immunization, especially those coinciding with previously described pulmonary inflammation associated with the use of the mucosal adjuvant, cholera toxin (CT). The major T cell population in the lungs of naive mice was CD4<sup>+</sup>, and these cells were shown to be predominantly of Th2 type as in vitro polyclonal stimulation resulted in IL-4, but not IFN-γ, production. After nasal immunization with influenza Ag alone, Th2 cytokine mRNA (IL-4 and IL-5) levels were increased, whereas there was no change in Th1 cytokine (IL-2 and IFN-γ) mRNA expression. The use of the mucosal adjuvant, CT, markedly enhanced pulmonary Th2-type responses; however, there was also a Th1 component to the T cell response. Using in vitro Ag stimulation of pulmonary lymphocytes, influenza virus-specific cytokine production correlated with the mRNA cytokine results. Furthermore, there was a large increase in CD4<sup>+</sup> Th cell numbers in lungs after nasal immunization using CT, correlating with the pulmonary inflammatory infiltrate previously described. Coincidentally, both macrophage-inflammatory protein-1α (MIP-1α) and MIP-1β mRNA expression increased in the lungs after immunization with Ag plus CT, while only MIP-1β expression increased when mice were given influenza Ag alone. Our study suggests a mechanism to foster Th1 cell recruitment into the lung, which may impact on pulmonary immune responses. Thus, while Th2 cell responses may be prevalent in modulating mucosal immunity in the lungs, Th1 cell responses contribute to pulmonary defenses during instances of intense immune stimulation.
Sphenoid Sinusitis
Authors: Daniel Lew, Frederick S. Southwick, William W. Montgomery, Alfred L. Weber, Ann S. Baker
Journal: New England Journal of Medicine (1983)

We studied 30 patients with infectious sphenoid sinusitis (15 acute cases and 15 chronic cases) in an effort to characterize the clinical presentation, bacteriology, and associated complications of this frequently misdiagnosed infection. Severe frontal, temporal, or retro-orbital headache that radiated to the occipital regions or pain in the trigeminal (V1 to V3) distribution or both were the most prominent presenting symptoms. In acute cases, purulent exudate was frequently seen in the middle and superior nasal turbinates. Computerized axial tomography or sinus tomography and cannulation of the sphenoid sinus proved to be the most useful diagnostic studies. Organisms detected in acute cases included streptococci other than Streptococcus pneumoniae (41 per cent), Staphylococcus aureus (29 per cent), and Str. pneumoniae (17 per cent). In chronic infections, gram-negative bacilli (43 per cent) and staphylococcal species (24 per cent) were the predominant organisms. In acute disease, early diagnosis and aggressive therapy, including surgical drainage, were important. Delay in treatment was always associated with serious morbidity or mortality. Fatal complications included cavernous sinus thrombosis and bacterial meningitis.
The Significance of Nonvisualization of Extrahepatic Bile Duct in Intravenous Radionuclide Cholescintigraphy with Special Reference to Acute Suppurative Cholangitis
Authors: MIAU-JU HUANG, YUN-FAN LI AW, KAI-YUAN TZEN
Journal: Clinical Nuclear Medicine (1984)

Intravenous radionuclide cholescintigraphy using Tc-99m HIDA was performed in 386 consecutive patients with suspected biliary disease. Among 365 patients with prompt hepatic uptake, the common bile duct was not visualized in 19 (5.2%). Biliary calculi with infection, especially suppurative cholangitis, is the most frequent condition responsible for this cholescintigraphic pattern. Conditions involving the common bile duct from extrinsic causes may also present this pattern. This pattern is a specific indicator of pathology in the common bile duct. In addition, it is diagnostic for acute suppurative cholangitis, with a sensitivity of 66.7%, a specificity of 90.5%, an accuracy of 88.3%, a positive predictive value of 42%, and a negative predictive value of 96.3%. Aside from mechanical obstructions, functional obstruction of a normal sized common duct that contained no calculi could also be detected by this pattern.
A REPORT OF THIRTY CASES OF CATARACT EXTRACTION WITH REFERENCE TO THE TREATMENT OF PROLAPSE OF IRIS FOLLOWING SIMPLE EXTRACTION.
Authors: LOUIS F. LOVE
Journal: JAMA (1898)

Undoubtedly the ideal method of cataract extraction is that in which the lens is removed without iridectomy. But in view of the much better results obtainable by the average operator with iridectomy I am inclined to think that simple extraction should be reserved for selected cases. Certainly it is safe to say that young operators should always use the combined method and wait until their judgment and skill are considerable before attempting simple extraction. The adoption of strict asepsis and antisepsis by the modern ophthalmic surgeon has, no doubt, made simple extraction of cataract more popular at the present day; but the great drawback still remains in the liability of prolapse of the iris coming on after the operation. On my return from Europe two years ago I determined to adopt simple extraction. Twenty out of thirty cataract cases were consecutively operated upon without iridectomy, and in four of them
THE PSYCHOLOGY OF COSMETIC SURGERY: A REVIEW AND RECONCEPTUALIZATION
Authors: David B Sarwer, Thomas A Wadden, Michael J Pertschuk, Linton A Whitaker
Journal: Clinical Psychology Review (1998)

This article discusses the psychology of cosmetic surgery. A review of the research on the psychological characteristics of individuals who seek cosmetic surgery yielded contradictory findings. Interview-based investigations revealed high levels of psychopathology in cosmetic surgery patients, whereas studies that used standardized measurements reported far less disturbance. It is difficult to fully resolve the discrepancy between these two sets of findings. We believe that investigating the construct of body image in cosmetic surgery patients will yield more useful findings. Thus, we propose a model of the relationship between body image dissatisfaction and cosmetic surgery and outline a research agenda based upon the model. Such research will generate information that is useful to the medical and mental health communities and, ultimately, the patients themselves. © 1998 Elsevier Science Ltd
Defective B-cell-negative selection and terminal differentiation in the ICF syndrome
Authors: Carla E. Blanco-Betancourt, Anne Moncla, Michèle Milili, Yun Liang Jiang, Evani M. Viegas-Péquignot, Bertrand Roquelaure, Isabelle Thuret, Claudine Schiff
Journal: Blood (2003)
The value of patch testing patients with a scattered generalized distribution of dermatitis: Retrospective cross-sectional analyses of North American Contact Dermatitis Group data, 2001 to 2004
Authors: Kathryn A. Zug, Robert L. Rietschel, Erin M. Warshaw, Donald V. Belsito, James S. Taylor, Howard I. Maibach, C.G. Toby Mathias, Joseph F. Fowler, James G. Marks, Vincent A. DeLeo, Melanie D. Pratt, Denis Sasseville, Frances J. Storrs
Journal: Journal of the American Academy of Dermatology (2008)
Impaired Interleukin 4 Signaling in T Helper Type 1 Cells
Authors: Hua Huang, William E. Paul
Journal: The Journal of Experimental Medicine (1998)

Cluster of differentation (CD)4+ T helper cells (Th)1s fail to produce interleukin (IL)-4. Even if restimulated in the presence of IL-4, a condition that induces IL-4–producing capacity in naive CD4+ T cells, Th1s fail to become IL-4 producers. We report that Th1 cells have a major impairment in IL-4 signaling. When compared to both Th2s and naive T cells, they display a striking diminution in phosphorylation of Stat6. They also show reduced phosphorylation of Janus kinase (JAK)-3 and insulin receptor substrate (IRS)-2 when compared to Th2s. Stat6 and JAK-3 are present in equivalent amounts in Th1s and Th2s, but IRS-2 protein levels are much lower in Th1s than in Th2s. Altered sensitivity to IL-4, the major inducer of the Th2 phenotype, may explain the stability of the Th1 state.