tbuckley/cabot-search huggingface dataset:
Abstract 1073: A systematic approach to identify the Ras-dependent C-RAF(Ser338)-phosphorylating kinase
Authors: Cory M. Johannessen, Jesse Boehm, Luke Hamm, Xiaoping Yang, Levi Garraway
Journal: Cancer Research (2011)

Abstract Phosphorylation of c-RAF at Ser338 is an absolute requirement for c-RAF activation and Ras-mediated signaling; however, definitive identification of the c-RAF(Ser338)-phosphorylating kinase has remained elusive. As a first step towards this end, we screened a collection of ∼600 expressible kinase open reading frames to determine which are sufficient to induce phosphorylation of c-RAF on Ser338. In total, 12 kinases induced c-RAF(Ser338) phosphorylation, including 9 Ser/Thr kinases, 1 kinase with unknown site specificity, 1 adapter factor and 1 scaffolding protein. Notably, two proteins previously shown to regulate c-RAF(Ser338) phosphorylation (PAK3 and KSR) also scored in this assay, highlighting the utility of this approach to uncover plausible effectors. We have initiated follow-up studies, including recombinant protein-based kinase assays and loss of function experiments, to characterize the kinase(s) responsible for Ras-mediated c-RAF(Ser338) phosphorylation in vivo. Given the inherent difficulty of targeting Ras-dependent cancers, a more detailed understanding of c-RAF phosphorylation and Ras-dependent activation may inform new therapeutic inroads to targeting these lesions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1073. doi:10.1158/1538-7445.AM2011-1073
Avulsion of the Gall Bladder from the Liver Bed
Authors: James M. Shannon
Journal: New England Journal of Medicine (1955)

ALTHOUGH the perforation of the acutely in-flamed gall bladder is quite common and associated hemoperitoneum and gastrointestinal hemorrhage have frequently been reported1 2 3 avulsion of the acutely edematous gall bladder from the liver bed without perforation but with bleeding from the liver has been reported only once in the past fifty years.4 Despite its rarity the condition appears to have characteristic diagnostic features, which might allow correct preoperative interpretation. Since the disease requires immediate surgical intervention it was considered worth while to present the following case to illustrate the clinical picture.Case ReportA 50-year-old merchant seaman entered the 8th Station . . .
PM-16 * IMMUNOSUPPRESSIVE FACTORS, MDSC AND ARGINASE, ARE ELEVATED IN DOGS WITH MALIGNANT GLIOMA
Authors: L. Pluhar, M. Goulart, C. Seiler, M. Olin
Journal: Neuro-Oncology (2014)

Immunotherapy for malignant gliomas has striking efficacy in rodent models but very limited effects in clinical trials, which may reflect immunological differences between induced and spontaneous tumors. The monocytes that heavily infiltrate GBM develop myeloid-derived suppressor cell (MDSC) phenotype, and these immunosuppressive cells are increased in GBM patients, but not in murine models. Canine primary brain tumors may offer a more faithful representation of the human disease due to similarities in clinical and pathobiological characteristics. We were recently first to identify MDSC in dogs and found significantly increased in number in dogs with advanced cancers. To add further support to pet dogs with glioma as a translational model, we assessed whether canine glioma patients also have elevated numbers of MDSC relative to healthy dogs. MDSC secrete arginase that removes L-arginine from the microenvironment profoundly impairing T cell proliferation and function. Therefore we also measured serum levels of arginase 1 in all dogs. The mean percentage of monocytic MDSC in peripheral blood of dogs with glioma (n = 26) was 7.51 ± 1.31, which was significantly greater than healthy controls (n = 10) with 0.74 ± 0.34 (P< 0.0001). The median percentages of granulocytic MDSC did not differ between dogs with glioma versus controls, 15.95% and 12.5% respectively. There were also significantly increased levels of arginase in the serum of dogs with gliomas, 8.00 ± 3.32 U/L, relative to that of healthy controls, 2.40 ± 1.40 U/L (P < 0.0001). These data demonstrate that some of the immunosuppressive mechanisms present in human gliomas patients are also found in dogs with malignant gliomas. These findings lend further support that the pet dog with spontaneous brain cancer that shares our environment is an excellent translational model for the human disease. We are currently working to correlate changes in numbers of MDSC and arginase levels in serum with disease burden as possible biomarkers for response to therapy.
"A Controlled Study"
Authors: Hamilton S. Davis
Journal: JAMA (1966)

To the Editor:—  Mainwaring and Brueckener subtitled their article on fibrinogen-transmitted hepatitis A Controlled Study (195:437, 1966). Perhaps I am being a bit overly critical, but it seems to be stretching a point to say that this  is  I presume the authors meant comparing the incidence of hepatitis in their nine fibrinogen-treated patients to the incidence in the 6,620 patients given whole blood over the same period of time. This sort of comparison is frequently resorted to and obviously has some merit. I don't doubt the validity of their conclusion that the incidence of hepatitis is much greater after fibrinogen than after whole blood. However, it does not seem cricket to whet the reader's appetite by including in the title the come-on phrase controlled study when the method used is not really rigidly controlled. This most certainly wasn't.  I feel let down by the overstatement and I
Intravenous Amiodarone for Arrhythmia Management
Authors: Amir Halkin
Journal: Annals of Internal Medicine (1998)

Letters15 March 1998Intravenous Amiodarone for Arrhythmia ManagementAmir Halkin, MD and Oren Shibolet, MDAmir Halkin, MDHadassah University Hospital; Mt. Scopus, Jerusalem 91240, IsraelSearch for more papers by this author and Oren Shibolet, MDHadassah University Hospital; Mt. Scopus, Jerusalem 91240, IsraelSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-6-199803150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their otherwise excellent review of intravenous amiodarone for arrhythmia management [1], Desai and colleagues misquoted the first reference they cited for the comparison of amiodarone with propafenone in conversion of recent-onset atrial fibrillation (reference 34 in their article, cited on page 297). This trial actually compared prophylactic amiodarone with placebo for the prevention of supraventricular and ventricular tachyarrhythmias in 77 patients recovering from coronary artery bypass surgery [2]. The investigators did not randomly assign patients to either propafenone or flecainide as stated by Desai and colleagues. Amiodarone and propafenone for conversion of atrial fibrillation or flutter ...References1. Desai AD, Chun S, Sung RJ. The role of intravenous amiodarone in the management of cardiac arrhythmias. Ann Intern Med. 1997; 127:294-303. Google Scholar2. Hohnloser SH, Meinertz T, Dammbacher T, Steiert K, Jahnchen E, Zehender M, et al. Electrocardiographic and antiarrhythmic effects of intravenous amiodarone: results of a prospective, placebo-controlled study. Am Heart J. 1991; 121:89-94. Google Scholar3. Larbuisson R, Venneman I, Stiels B. The efficacy and safety of intravenous propafenone versus intravenous amiodarone in the conversion of atrial fibrillation or flutter after cardiac surgery. J Cardiothorac Vasc Anesth. 1996; 10:229-34. Google Scholar4. Fresco C, Proclemer A. Clinical challenge II. Management of recent onset atrial fibrillation. PAFIT-2 investigators. Eur Heart J. 1996; 17(Suppl C):41-7. Google Scholar5. Maisel WH, Kuntz KM, Reimold SC, Lee TH, Antman EM, Friedman PL, et al. Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital. Ann Intern Med. 1997; 127:281-4. Google Scholar Author, Article, and Disclosure InformationAffiliations: Hadassah University Hospital; Mt. Scopus, Jerusalem 91240, Israel PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 March 1998Volume 128, Issue 6Page: 505KeywordsAcute myocardial infarctionAdverse reactionsArrhythmiaAtrial fibrillationCoronary arteriesDrugsHeart rateRandomized trialsSurgeryTachycardia Issue Published: 15 March 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
The Definition and Scope of Clinical Pharmacology
Authors: Richard I. H. Wang
Journal: JAMA (1980)

CLINICAL pharmacology has grown out of a need to extend the discipline of basic pharmacology into clinical practice. A similar evolution of a clinical science took place when clinical pathology became established as a discipline separate from basic pathology. The progenitors of clinical pathology saw that a new type of specialist in pathology, one with firm roots in clinical medicine, was necessary if the study of pathology was to progress in providing improved patient care. Clinical pathology has been an established and recognized discipline for more than half a century. The growth and development of clinical pharmacology has proceeded much more slowly than that of clinical pathology. The earliest systematic clinical investigations into drugs were carried out by Harry Gold, MD, and his associates about 50 years ago. However, it was not until 1952 that Gold first voiced the need for the establishment of a separate discipline incorporating basic pharmacology
Unified training grade
Authors: T. J Bayley
Journal: BMJ (1995)

The report of the working party on the unified training grade1 is the first piece of a jigsaw that will provide the picture for higher specialist training recommended in the Calman report.2 But even after elision of the registrar and senior registrar grades, in Britain, unlike in other members of the European Union, specialist training will comprise two grades: senior house officer and specialist registrar.

Entry to, assessment of progress through, and exit from the new specialist registrar grade will be managed by postgraduate deans in close collaboration with the medical royal colleges. Before the new grade is implemented satisfactory appointment systems and instruments for assessment will have to be developed and the curriculums for all specialties and other guidance will need to be published. All specialties are expected to begin transitional arrangements within one year of the commissioning date, but much more information, particularly the numbers for the grade in each specialty, is urgently needed. Some specialties are likely to make rapid progress to a steady state …
Investigation of Relation between Use of Oral Contraceptives and Thromboembolic Disease. A Further Report
Authors: M. P. Vessey, R. Doll
Journal: BMJ (1969)

The results of a previous study of the use of oral contraceptives by married women discharged from hospital with a diagnosis of thromboembolic disease in the years 1964-6 were reported by us last year. The present paper adds results relating to patients discharged during 1967 and a few data, that could not be sought previously, for patients discharged with cerebral or coronary thrombosis from three of the hospitals in the earlier period.Of 84 patients with deep-vein thrombosis or pulmonary embolism 42 (50%) had used oral contraceptives during the month preceding the onset of their illness, while only 23 of the 168 controls (14%) had done so. No differences in risk were found either for the types of preparation or for the duration of use. After allowance for age and height, the patients with venous thromboembolism were about 10 lb. (4,535 g.) heavier than the control patients, irrespective of whether they were using oral contraceptives or not. No appreciable difference was found between the smoking habits of patients with and without venous thromboembolism treated during 1967, nor between women who were using oral contraceptives and those who were not. The trend in hospital admissions for venous thromboembolism with time corresponded to the trend in the use of oral contraceptives, and there was no evidence to suggest that the number of admissions was affected by publicity about the risk of using the preparations. Of 19 patients with cerebral thrombosis 11 (58%) had been using oral contraceptives, compared with an expected figure of 3.5 from the experience of the control subjects. All the published data (clinical, angiographic, and post-mortem) show that the thrombosis affects the cerebral arteries rather than the cerebral veins. Of 17 patients with coronary thrombosis 2 (12%) had been using oral contraceptives, compared with an expected figure of 2.1. The patients with coronary thrombosis smoked more than the control patients and were, on average, 8.3 lb. (3,765 g.) heavier than control women of the same age and height.The new evidence strengthens the belief that oral contraceptives are a cause of venous thromboembolism and cerebral thrombosis but does not indicate that they are a cause of coronary thrombosis.
Orofacial granulomatosis worsened by chocolate: results of patch testing to ingredients of Cadbury's chocolate
Authors: S.M. Taibjee, L. Prais, I.S. Foulds
Journal: British Journal of Dermatology (2004)

We report a 26‐year‐old man with orofacial granulomatosis, characterized by granulomatous swelling of his lips and oral ulceration, confirmed on biopsy. After only partial response to oral steroids, he was referred for patch testing. He volunteered that his symptoms worsened after eating chocolate. Initial patch testing to Cadbury's drinking chocolate (usually consumed by our staff) showed a positive result at 48 h. We subsequently patch tested him to the ingredients of Cadbury's chocolate supplied by the company, including: cocoa liquor, cocoa butter, soya‐based lecithin (emulsifier), rape‐based lecithin (emulsifier) and dark chocolate. He was clearly positive to cocoa liquor, the complex natural product extracted from cocoa beans, establishing that cocoa itself was responsible for his chocolate intolerance (Fig. 1). Flare‐up of our patient's condition during patch testing confirmed the clinical relevance of our findings (Fig. 2).
RNA-binding protein insulin-like growth factor II mRNA-binding protein 3 expression promotes tumor invasion and predicts early recurrence and poor prognosis in hepatocellular carcinoma
Authors: Yung‐Ming Jeng, Cheng‐Chi Chang, Fu‐Chang Hu, Han‐Yi E. Chou, Hsin‐Lien Kao, Ting‐Huang Wang, Hey‐Chi Hsu
Journal: Hepatology (2008)

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an RNA-binding protein expressed in embryonic tissues and multiple cancers. To investigate the role of IMP3 in hepatocellular carcinoma (HCC), its protein expression in the surgically resected unifocal tumors of 377 HCC patients (296 men and 81 women) with ages ranging from 7 to 88 years (mean, 55.49 years) was analyzed by immunohistochemistry. IMP3 was expressed in 255 (67.6%) of 377 resected unifocal primary HCCs. IMP3 protein was predominantly expressed in tumor border and invasive front, and it was more abundant in the satellite nodules and tumor thrombi than in the main tumors. The expression correlated with high α-fetoprotein (>200 ng/mL, P < 1 × 10−7), larger tumor size (>5 cm, P = 0.006), high tumor grade (P < 1 × 10−7), and high tumor stage with vascular invasion and various degrees of intrahepatic metastasis (P < 1 × 10−7). IMP3 expression predicted early tumor recurrence (P < 1 × 10−7) and was a strong indicator of poor prognosis (P < 0.0001). Depletion of IMP3 with RNA interference in HCC cell line HA22T caused a decrease in cell motility, invasion, and transendothelial migration. Microarray analysis revealed that IMP3 depletion was associated with downregulation of multiple genes involved in tumor invasion. Conclusion: Our results indicate that IMP3 plays an important role in tumor invasion and metastasis and is a strong prognostic factor for patients with HCC. (HEPATOLOGY 2008.)
Surgical management of an esophagotracheal fistula as a severe, late complication of repeated endoscopic stenting treatment
Authors: R. Ladurner, C. Schulz, P. Jacob, M. Küper, T. Kratt, S. Preyer, A. Königsrainer
Journal: Endoscopy (2007)

An acquired, nonmalignant esophagotracheal fistula is an uncommon and difficult problem in clinical management. A few reports [1] [2] [3] [4] [5] describe various clinical examples and treatment solutions to the problem, but due to the rarity of the problem, guidelines for effective management have not been established.
The essence remains unchanged
Authors: Helen Ruth Offman
Journal: BMJ (2004)

A recent Filler describing the author's childhood in a medical family prompted memories of my own. My parents had a joint practice in Kirkby, an industrial estate near Liverpool once famously described as “the septic tank of the North.” Until I was 11 years old we lived next door to the surgery, which was purpose built although rather unfit for its function.

A row of heavy filing cabinets separated the receptionists' “office” from the waiting area: this tiny stolen space also doubled as the nurses' treatment room. My mother's room—shared …
Clinical Observations on Veno-occlusive Disease of the Liver in Jamaican Adults
Authors: K. L. Stuart, G. Bras
Journal: BMJ (1955)

FUNCTION JBRowuuL based on the necropsy, the microscopical preparation, and the radiograph.The task has given me many hours of happy toil.I hope that I have in a small way discharged the obligation of Dr. George Oliver to "encourage the applica- tion of physiological knowledge to the prevention and cure of disease."
Study of gene–gene interactions for endophenotypic quantitative traits in Chinese asthmatic children
Authors: I. H. S. Chan, N. L. S. Tang, T. F. Leung, W. Huang, Y. Y. O. Lam, C. Y. Li, C. K. Wong, G. W. K. Wong, C. W. K. Lam
Journal: Allergy (2008)

Background: Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene–gene interactions could provide insight into the pathophysiology of asthma. Methods: We investigated the interactions among 18 single‐nucleotide polymorphisms in eight candidate genes for plasma total immunoglobulin E (IgE) concentration and peripheral blood (PB) eosinophil count in 298 Chinese asthmatic children and 175 controls. Generalized multifactor dimensionality reduction and generalized linear model were used to analyze gene–gene interactions for the quantitative traits. Results: A significant interaction was found between R130Q in IL13 and I50V in IL4RA for plasma total IgE concentration, with a cross‐validation (CV) consistency of nine of 10 and a prediction error of 41.1% ( P = 0.013). Plasma total IgE concentration was significantly higher in the high‐risk than the low‐risk groups ( P &lt; 0.0001). For PB eosinophil count, significant interaction was found between C‐431T in TARC and Rsa I_in2 in FCERIB , with a CV consistency of nine of 10 and a prediction error of 40.2% ( P = 0.009). PB eosinophil count was significantly higher in the high‐risk group than the low‐risk groups ( P &lt; 0.0001). Generalized linear model also revealed significant gene–gene interaction for the above two endophenotypes with P = 0.013 for plasma total IgE concentration and P = 0.029 for PB eosinophil count respectively. Conclusions: Our data suggest significant interactions between IL13 and IL4RA for plasma total IgE concentration, and this is the first report to show significant interaction between TARC and FCERIB for PB eosinophil count in Chinese asthmatic children.
Assessment of hepatic vitamin E status in adult patients with liver disease
Authors: A Nagita, M Ando
Journal: Hepatology (1997)

No published reports compare hepatic alpha-tocopherol (adjusted for hepatic lipid content) with indicators of blood alpha-tocopherol in adult patients with various liver diseases. alpha-Tocopherol was simultaneously measured in liver biopsy tissues and blood from 66 subjects (9 comparison patients hospitalized for biliary tract surgery, 13 with chronic persistent hepatitis, 9 with chronic aggressive hepatitis, 10 with acute hepatitis, 10 with cirrhosis, 7 with both cirrhosis and hepatic cell carcinoma, and 8 with fatty liver). Hepatic, erythrocyte, and plasma alpha-tocopherol concentrations were measured, as were hepatic and serum lipids. The ratios of alpha-tocopherol to total lipid concentrations (Toc/TL ratios) in plasma and liver were calculated. In both comparison patients and patients with chronic persistent hepatitis and fatty liver, hepatic alpha-tocopherol concentrations were strongly correlated with hepatic triglyceride and total lipid concentrations (r = .72, P < .001; and r = .75, P < .001, respectively); the relationships (slopes) when hepatic alpha-tocopherol concentrations were compared with hepatic triglyceride and total lipid concentrations were similar in these patients and in all subjects. No strong correlations were found between hepatic and blood alpha-tocopherol parameters in all subjects. These results suggest that hepatic alpha-tocopherol is present at similar concentrations in triglycerides as well as total cholesterol and phospholipids and that neither plasma Toc/TL ratios nor erythrocyte alpha-tocopherol concentrations are useful indicators of hepatic vitamin E status. The hepatic Toc/TL ratio may be useful to assess total hepatic vitamin E status.
The oncogenic potential of human papillomaviruses: a review on the role of host genetics and environmental cofactors
Authors: V.K. Madkan, R.H. Cook-Norris, M.C. Steadman, A. Arora, N. Mendoza, S.K. Tyring
Journal: British Journal of Dermatology (2007)

Human papillomaviruses (HPVs), with over 100 genotypes, are a very complex group of human pathogenic viruses. In most cases, HPV infection results in benign epithelial proliferations (verrucae). However, oncogenic types of HPV may induce malignant transformation in the presence of cofactors. For example, over 99% of all cervical cancers and a majority of vulval, vaginal, anal and penile cancers are the result of oncogenic HPV types. Such HPV types have been increasingly linked to other epithelial cancers involving the skin, larynx and oesophagus. Although viral infection is necessary for neoplastic transformation, evidence suggests that host and environmental cofactors are also required. Research investigating HPV oncogenesis is complex and quite extensive. The inability to produce mature HPV virions in animal models has been a major limitation in fully elucidating the oncogenic potential and role of associated cofactors in promoting malignant transformation in HPV-infected cells. We have reviewed the literature and provide a brief account of the current understanding of HPV oncogenesis, emphasizing the role of genetic susceptibility, immune response, and environmental and infectious cofactors.