tbuckley/cabot-search huggingface dataset:
Abstract 4163: Determination of synthetic lethal interactions in KRAS oncogene dependent cancer cells reveals novel therapeutic targeting strategies
Authors: Miriam Molina-Arcas, David Hancock, Michael Steckel, Julian Downward
Journal: Cancer Research (2012)

Abstract Oncogenic mutations in RAS genes are very common in many human cancers, including those affecting the lung and the gastro-intestinal tract. RAS mutant cancers tend to be resistant to most targeted therapies, emphasising a clear need for the development of more effective treatments. Oncogenic KRAS deregulates numerous downstream pathways, resulting in cells with well-characterised selective advantages, but also less well understood vulnerabilities. In a panel of twenty-six non-small cell lung cancer (NSCLC) cell lines, half of which carry an activating KRAS mutation, knock-down of KRAS using siRNA indicates that KRAS mutant cells require KRAS expression to maintain viability. Moreover, KRAS depletion produces a clear inhibition of ERK and AKT signaling. As RAS proteins cannot be inhibited directly at present, we tested small molecule inhibitors targeting pathways directly controlled by RAS, such as RAS/RAF/MEK or PI3K/AKT/mTOR, as well as drugs directed against other targets (such as HSP90, topoisomerases or the proteasome) in order to affect tumour-specific vulnerabilities associated with the oncogenic state. Viability assays showed that cells harbouring an activated KRAS oncogene were more sensitive to MEK, RAF and IGF-1R inhibitors than cells carrying only wild-type KRAS alleles. In contrast, no differential loss of cell viability was observed when cells were treated with either PI3K or AKT inhibitors. Combinations of IGF-1R inhibitors with MEK or RAF inhibitors resulted in a synergistic anti-proliferative effect in KRAS mutant cell lines. Similar effects were observed upon simultaneous treatment with PI3K and MEK inhibitors. However, in this case, wild-type KRAS cells were also affected by PI3K inhibition, resulting in a less-pronounced differential effect. Pathway inhibition analysis showed that, whereas MEK and PI3K inhibitors respectively decreased ERK and AKT phosphorylation in all cell lines, IGF1R inhibitors decreased AKT phosphorylation only in KRAS mutant cell lines. Inhibition of AKT phosphorylation correlates with effectiveness of IGF-1R inhibitor in blocking cell proliferation. Mechanistically, it appears that mutant KRAS activation of PI3K requires coordinate input from IGF-1R. These findings suggest potential therapeutic strategies for NSCLC tumours harbouring KRAS mutations. 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 4163. doi:1538-7445.AM2012-4163
Better benefits for health: plan to implement the central recommendation of the Acheson report
Authors: D. Black, J N Morris, C. Smith, P. Townsend
Journal: BMJ (1999)

As authors of the Black report, we welcome the report of the independent inquiry into inequalities in health by the scientific advisory group under the chairmanship of Sir Donald Acheson. 1 2 In particular, we welcome the attention given in the report to the increasing problems caused since the late 1970s by the rapidly widening gap in living standards. We also welcome recommendation number 3 (among the 39 principal recommendations) which specifies the need for policies to “reduce income inequalities and improve the living standards of households in receipt of social security benefits.”1 The report specifies that benefits in cash or in kind must be increased to reduce “poverty in women of childbearing age, expectant mothers, young children and older people.” Nine other recommendations (numbers 8, 13, 20, 21, 22, 27, 31, 35, 36) were explicitly linked to recommendation 3, reinforcing the call for integrated action to alleviate unemployment and the deprived condition of many ethnic minority groups, elderly and disabled people, and families with children; and increase benefit levels and real living standards. Another 10 recommendations are concerned with meeting material needs in schools, housing, the environment, transport, and diet.

#### Summary points

The 1998 Acheson report echoes the findings of the 1980 Black report that the gap in inequalities in health has been steadily increasing and that differences in material deprivation are a major cause of the increase

The likely effects on inequalities in health of the chief policies implemented in the 1980s and 1990s still need to be estimated so that strategies to improve health can be improved

The level of benefit that is minimally sufficient to maintain health and effective working and social capacity among different types of families needs to be defined and related to a programme to improve benefits

A staged programme of the action needing …
Coronavirus as a possible cause of severe acute respiratory syndrome
Authors: JSM Peiris, ST Lai, LLM Poon, Y Guan, LYC Yam, W Lim, J Nicholls, WKS Yee, WW Yan, MT Cheung, VCC Cheng, KH Chan, DNC Tsang, RWH Yung, TK Ng, KY Yuen
Journal: The Lancet (2003)

An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients.We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked.Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus.A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.
Modern Day Menstrual Folklore
Authors: Loudell F. Snow
Journal: JAMA (1977)

Clinicians are often unaware of the folk medical beliefs of their patients or consider them to be harmless and unimportant. Such beliefs are instrumental in shaping patient behavior, however, and may contribute to negative health practices. The information presented here demonstrates that attitudes toward a single bodily function, menstruation, may adversely affect women's body image, perception of disease causation, diet, willingness to take medication, contraceptive use, and the ability to plan pregnancies. The data are part of a pilot study in which patients in a clinic serving a multiethnic low-income population were questioned about their knowledge and beliefs concerning the female reproductive cycle. It is concluded that health personnel should strive to learn what women know and believe about their bodies and how they function, to improve health care provision.
Cardioprotective Effect of Diazoxide Is Mediated by Activation of Sarcolemmal but Not Mitochondrial ATP-Sensitive Potassium Channels in Mice
Authors: Masashi Suzuki, Tomoaki Saito, Toshiaki Sato, Masaji Tamagawa, Takashi Miki, Susumu Seino, Haruaki Nakaya
Journal: Circulation (2003)

Background— We recently demonstrated that the sarcolemmal ATP-sensitive potassium (sarcK ATP ) channel plays a key role in cardioprotection against ischemia/reperfusion injuries in Kir6.2-knockout (KO) mice. In the present study, we evaluated the effects of diazoxide, a mitochondrial ATP-sensitive potassium (mitoK ATP ) channel opener, on ischemia-induced myocardial stunning in sarcK ATP channel-deficient mice. Methods and Results— Langendorff-perfused hearts of wild-type (WT) and KO mice were subjected to global ischemia/reperfusion. Diazoxide improved the recovery of contractile function in WT hearts but not in KO hearts. Treatment with HMR1098 (a sarcK ATP channel blocker) but not 5-hydroxydecanoate (a mitoK ATP channel blocker) abolished the cardioprotective effect of diazoxide in WT hearts. In coronary-perfused WT ventricular muscle preparations, action potential shortening during ischemia was accelerated in the presence of diazoxide. Conclusions— Diazoxide enhances action potential shortening during ischemia by activating sarcK ATP channels and provides cardioprotection in mouse hearts.
Timing of Umbilical Cord Clamping at Birth in Full-term Infants
Authors: William Oh
Journal: JAMA (2007)

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 Journals 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 2024 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
Effect of Calcium Antagonists in Experimental Asthma
Authors: Earle B. Weiss, Jeffrey Markowicz, Linda Barbero
Journal: Allergy (1982)

Verapamil was found to be an effective inhibitor of isometric tension in in vitro , experimental anaphylaxis in guinea pig trachealis smooth muscle. The mean IC 50 for protection studies was 2×10 −4 M; the drug was also effective as a bronchoreversal agent. The inhibitory effect of verapamil upon the initial rate of isometric muscle tension suggests an action beyond simple calcium channel inhibition. No inhibition of tracheal mast cell histamine release was observed. Verapamil was slightly more potent than theophylline in this in vitro anaphylactic model.
INFLUENZA IN CHILDREN.
Authors: WM. CARVER WILLIAMS
Journal: JAMA (1903)

It is the writer's conviction that influenza is a more malignant malady in children than is generally acknowledged (a conviction fortified by his own experience and further strengthened by material gathered among his friends and from the literature), which has led him to venture this paper. Without being able to furnish much, if anything, that is new on the subject, it yet seems justifiable here to emphasize some of the manifestations and possible calamities which may be traced to this disease. Influenza vera, when the victim is a child, differs from the same disease in adults in proportion to the difference in constitution, vital resistance and recuperative power. It should not be forgotten in this connection that the disease is of a markedly toxic nature. The admirable article in Ashby and Wright's work states, however, that children are less likely to have some of the ordinary symptoms, such as backache,
STUDIES ON THE BACTERIOPHAGES OF HEMOLYTIC STREPTOCOCCI
Authors: Richard M. Krause
Journal: The Journal of Experimental Medicine (1958)

The lysis of cell walls of hemolytic streptococci by a phage-associated lysin has been described. A method is presented for preparing the lysin from Group C streptococcal phage lysates. Following lysis almost all of the cell wall carbohydrate is recovered in solution. This material has the serological reactivity, physical-chemical properties, and values for nitrogen, rhamnose, and glucosamine similar to those of the carbohydrate isolated from the cell walls by the Streptomyces albus enzyme. Group C carbohydrate isolated by either enzyme inactivates Group C bacteriophage. The protein liberated by the lysin from Group A Type 6 cell walls gives a type-specific precipitin reaction with homologous rabbit antiserum. Preliminary data are presented on the ammonium sulfate fractionation and the electrophoretic separation of a protein fraction with the serological reactivity of M protein.
Increased prevalence of psoriasis in patients with coronary artery disease: results from a case–control study
Authors: D. Picard, J. Bénichou, C. Sin, C. Abasq, E. Houivet, R. Koning, A. Cribier, B. Veber, F. Dujardin, H. Eltchaninoff, P. Joly
Journal: British Journal of Dermatology (2014)

The incidence of myocardial events has been reported to be increased in patients with psoriasis.To investigate whether psoriasis is an independent risk factor for coronary artery disease (CAD).We compared the prevalence of psoriasis between case patients with a diagnosis of CAD based on coronary angiography findings and control patients with no CAD referred to the emergency surgery department for an acute noncardiovascular condition. Case and control patients were examined for the presence of psoriasis by two dermatologists. The prevalence of psoriasis was compared among patients with CAD according to CAD severity. Five-hundred cases and 500 age- and sex-matched controls were included.Using matched univariate analysis, the prevalence of psoriasis was about twofold higher in CAD case patients than in control patients [8·0% vs. 3·4%, odds ratio (OR) 2·64; 95% confidence interval (CI) 1·42-4·88]. Using unconditional multivariate analysis, the association of psoriasis with CAD appeared to be borderline significant (OR 1·84; 95% CI 0·99-3·40). Psoriasis in patients with CAD was significantly associated with three-vessel involvement relative to one-or two-vessel involvement (13·1% vs. 6·1%; OR 3·07; 95% CI 1·50-6·25).The prevalence of psoriasis is twofold higher in patients with CAD than in control patients without CAD. It is associated with a more severe coronary artery involvement.
Insulin Resistance: A Common Feature of Diabetes Mellitus
Authors: C. Ronald Kahn
Journal: New England Journal of Medicine (1986)

In a classic article in 1965, Shipp et al. reviewed the subject of insulin resistance in diabetes (defined as an insulin requirement of more than 200 U per day) and declared it a rare complication that occurred in only about 0.01 percent of all diabetic patients seen over a 20-year period at the Joslin Diabetes Center.1 All the patients were insulin-treated, and in most, antibodies to insulin could be found in the circulation. Three articles in this issue of the Journal,2 3 4 as well as one in last week's issue,5 dramatically illustrate how our definition of insulin resistance has changed. . . .
Thoracic Aneurysm
Authors: SHELTON P. SANFORD
Journal: Annals of Internal Medicine (1931)

Article1 May 1931Thoracic AneurysmStatistical Study of Seventy-one Cases*SHELTON P. SANFORD, A.M., M.D.SHELTON P. SANFORD, A.M., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-11-1417 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe object of this paper is to present a statistical study of cases of aneurysm of the thoracic aorta at the Grady Hospital, Emory University Division. A series of seventy-one was selected. Necropsy was performed in thirty-two of these. A number of cases have been discarded because the diagnosis seemed uncertain and necropsy was not done. All patients were colored.The seventy-one cases have been studied with regard to the following twenty-two points:1. Age2. Sex3. Admission Diagnosis4. First Symptom5. Chief Complaint6. Duration7. Initial Lesion8. Wasserman Reaction9. Roentgenograms10. Aortic Second Sound... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: SHELTON P. SANFORD, A.M., M.D.Affiliations: Atlanta, Ga.*From the Emory University Division, Grady Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAN UNUSUAL CASE OF AORTIC ANEURYSM*S. P. SANFORD, M.D. 1 May 1931Volume 4, Issue 11Page: 1417-1423KeywordsAneurysmsAortaLesions ePublished: 1 December 2008 Issue Published: 1 May 1931 PDF downloadLoading ...
Tc-99m Hexamethylpropylene Amine Oxime Scintigraphy in the Diagnosis of Brain Death and Its Implications for the Harvesting of Organs Used for Transplantation
Authors: RICHARD W. KURTEK, K. KAY-YIN LAI, W. NEWLON TAUXE, BENJAMIN H. EIDELMAN, JOHN J. FUNG
Journal: Clinical Nuclear Medicine (2000)

Purpose Diagnosing brain death is important in managing the comatose patient for whom the continuation of life support is being questioned and when organ harvesting is being considered. The virtual immediate localization of Tc-99m HMPAO to cerebral and cerebellar tissue provides an index of blood perfusion, and its absence denotes brain death. Other methods for assessing brain death include cerebral angiography, MRI, CT imaging after inhalation of stable xenon, electroencephalography, and clinical examination. The contrast material used for angiography may damage harvested organs, and the other studies have significant errors. MRI, CT imaging, and angiography are unsuitable for bedside use. Methods Twenty-three patients, who presented with head trauma, prolonged anoxia or intrinsic brain disease (e.g., glioblastoma multiforme) and who were brain-dead by clinical examination criteria, were referred to the nuclear medicine division for verification of brain death. For adults, approximately 25 mCi Tc-99m hexamethylpropylene amineoxime (HMPAO) was administered intravenously. All patients but one were imaged using a mobile scintillation camera at the bedside. Results We demonstrated (1) both cerebral and cerebellar perfusion, (2) neither cerebral nor cerebellar perfusion, (3) cerebral without cerebellar perfusion, and (4) cerebellar without cerebral perfusion. Patients without cerebral perfusion were diagnosed as brain-dead. The significance of a viable cerebellum in the absence of cerebral viability was not fully appreciated, although organs were harvested from such patients. We determined how well the clinical examination criteria held up in the diagnosis of brain death against the new gold standard of Tc-99m HMPAO scintigraphy: Clinical examination criteria correctly predicted brain death only 83% of the time compared with HMPAO scintigraphy. Conclusions Brain death assessment by Tc-99m HMPAO scintigraphy has proved to be a reliable, safe, and cost-effective bedside method and may have practical application in the assessment of brain death in potential cadaveric donors.
Inosinic acid dehydrogenase activity in the Lesch-Nyhan syndrome
Authors: D. Michael Pehlke, John A. McDonald, Edward W. Holmes, William N. Kelley
Journal: Journal of Clinical Investigation (1972)

Inosinic acid dehydrogenase was evaluated in normal subjects and in patients with the Lesch-Nyhan syndrome. A significant difference in activity was found between erythrocytes derived from normal controls (1.21+/-0.47 pmoles/hr per mg protein) and from 15 patients with the Lesch-Nyhan syndrome (6.72+/-6.23 pmoles/hr per mg protein). However, no difference in activity was demonstrable in muscle or leukocytes derived from normal and Lesch-Nyhan patients. The increased activity of inosinic acid dehydrogenase in erythrocytes from patients with the Lesch-Nyhan syndrome is due to stabilization of the enzyme in vivo as well as the absence of an inhibitor which is present in erythrocytes from normal subjects.
The Inhibition of Insulin Action by Toxaemias and its Explanation: A Preliminary Communication
Authors: R. D. Lawrence
Journal: BMJ (1926)

DItRING 1925 I lhadl undeir miy calre in All Saints' Hospital 25 cases of enilarged prostate for which pro3'.,tat+atectoilnv was performed.These cases I have sulh,sequenitly followed up in the out-patient department fol tlie ensuincT two moniths or longer.
Reduced structural proteins in the conjunctival epithelium in allergic eye disease
Authors: J. L. Hughes, P. M. Lackie, S. J. Wilson, M. K. Church, J. I. McGill
Journal: Allergy (2006)

Aims: Allergic eye disease affects up to 20% of the population with varying severity. The conjunctival epithelium plays a key role in allergic eye disease. The purpose of this study was to determine whether the conjunctival epithelium is abnormal in allergic eye disease. Methods: Conjunctival biopsy samples were taken from patients with seasonal allergic conjunctivitis (SAC) ‘in’ and ‘out of season’ and nonatopic control subjects. Specimens were fixed in glycol methacrylate, 2 μ m serial sections cut and Image‐J used to assess the sites and areas of immuno‐staining. Results: E‐cadherin, CD44, keratins K5/6, K8, K13, K14, K18 and pan‐keratin immuno‐staining were all significantly lower in patients ‘out of season’ compared with normal controls. No structural differences in the epithelium were observed between the two groups. The epithelium of patients ‘in season’ was thicker and immuno‐staining of the above markers similar to controls. Conclusions: The expression of a wide spectrum of epithelial cell adhesion proteins and cytoskeletal elements is downregulated in the conjunctiva of SAC patients ‘out of season’ compared with normal controls. We suggest that this could have an important impact on the ability of the epithelium to protect itself against allergen penetration, potentially influencing the development and course of allergic eye disease and offering a novel area for therapeutic control.
Improving the safety of oxygen therapy in hospitals: summary of a safety report from the National Patient Safety Agency
Authors: T. Lamont, D. Luettel, J. Scarpello, B R. O'Driscoll, S. Connew
Journal: BMJ (2010)

Oxygen is used commonly and can save lives by preventing severe hypoxaemia.1 However, serious harm is possible if oxygen is not managed properly and the risks are poorly understood by trainee doctors and others.2 Underuse of oxygen can cause hypoxic organ damage, whereas overuse may harm neonates or cause hypercapnic respiratory failure in patients with chronic obstructive pulmonary disease.

From December 2004 to June 2009, healthcare staff reported 281 serious incidents relating to oxygen use to the National Patient Safety Agency in England and Wales. Among these incidents, poor oxygen management seems to have caused nine deaths and may have contributed to a further 35 deaths. A typical incident report reads: “Patient [has] known type 2 respiratory failure with a diagnosis of COPD [chronic obstructive pulmonary disease] and who had previously required BIPAP [bilevel positive airway pressure] to control hypercapnia, [and was] switched to 15 litres O2 via face mask by nurse as he had low saturations, without the advice of a doctor. The patient was seen several hours later, GCS3 [Glasgow coma score 3], profound respiratory acidosis. Cardiac arrest and died that afternoon.”

This summary is based on a safety report (known as a “rapid response …