tbuckley/cabot-search huggingface dataset:
Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma
Authors: A Tannapfel
Journal: Gut (2003)

The Raf/MEK/ERK (mitogen activated protein kinase-MAPK) signal transduction cascade is an important mediator of a number of cellular fates, including growth, proliferation, and survival. The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic Ras, leading to cooperative effects in cells responding to growth factor signals.The aim of this study was to elucidate a possible function of BRAF in liver tumours.Mutations of BRAF and KRAS were evaluated in 25 hepatocellular carcinomas (HCC) and in 69 cholangiocarcinomas (CC) by direct DNA sequencing analyses after microdissection. The presence of active intermediates of the MAPK pathway was assessed immunohistochemically. The results obtained were correlated with histopathological variables and patient survival.Activating BRAF missense mutations were identified in 15/69 CC (22%) and in one case of tumour surrounding liver. KRAS mutations were found in 31 of 69 (45%) CC examined and in two cases of tumour surrounding non-neoplastic liver tissue. In HCC, neither BRAF nor KRAS mutations were detected. All 31 CC with KRAS mutations had an intact BRAF gene. We failed to observe a correlation between BRAF or KRAS mutations and histopathological factors or prognosis of patients.Our data indicate that BRAF gene mutations are a relatively common event in CC but not in HCC. Disruption of the Raf/MEK/ERK (MAPK) kinase pathway, either by RAS or BRAF mutation, was detected in approximately 62% of all CC and is therefore one of the most frequent defects in cholangiocellular carcinogenesis.
The Incidence, Clinical and Pathological Classification of Cancer of the Prostate
Authors: H. Grabstald
Journal: CA A Cancer Journal for Clinicians (1965)

ing 1965.1An appalling numberof cases!In 1958 and 1959, the age-adjusted death i-ate from cancer of the prostate was 14.5 per 100,000 men in the United States.2'Â°'By 1961, this rate had risen to 15.7 for white and 19.4 for nonwhite men.In 1962, approximately 14,000 men in the United States died of pros tatic cancer.It is the leading cause of cancer deaths in men over 75@3 The autopsy incidence varies with age and with the care and diligence with which prostatic cancer is sought.In different series of autopsies, cancer has been detectedin 14 to 80%.The high, 80%, was in men in their ninth decade (Table 1 ) .â€ẫ€˜¿A significant number of clinically unsuspected cancei-s am-c found when examining prostatic specimens removed for â€oe¿ benigndisease.â€•In a series i-cported in 1961, of 748 such specimens, the incidence of prostatic cancer was 7@7% 50 Sixty years eai-liei-, Albam-ran and HallÃ©had noted a 14% incidence under similar conditions.In two other series of â€oe¿ benignpros tateâ€• specimens surgically removed, the incidence of cancei-was 4.0 and 9.2%.@@-@Â°Thelow incidence of 4.0 probably reflects the rigid selection of cases studied in that series, which rep resented transurethi-al resections per formed at the Mayo Clinic.20-35Among 25,000 transu rethral prostatectomies performed at the Mayo Clinic during the past 25 years, cancei-was diagnosed in 13% of these specimens.Obviously,
Quantitative and Qualitative Comparison of the Lipids in Platelets, Aortic Intima, and Mural Thrombi
Authors: E. B. Smith
Journal: Cardiovascular Research (1967)

Quantitative analysis of platelet lipids showed that the amount of cholesterol present is too low to make a significant contribution to the cholesterol in atherosclerotic lesions. Platelet mural thrombi which were in contact with intact aortic intima showed no increase in lipid compared to fresh platelets. There is thus no evidence that they trap or accumulate plasma lipid.
External Validation of the Fatty Liver Index for Identifying Nonalcoholic Fatty Liver Disease in a Population-based Study
Authors: Edith M. Koehler, Jeoffrey N.L. Schouten, Bettina E. Hansen, Albert Hofman, Bruno H. Stricker, Harry L.A. Janssen
Journal: Clinical Gastroenterology and Hepatology (2013)
Population-based screening using prostate-specific antigen testing reduced prostate cancer mortality
Authors: Richard M. Hoffman
Journal: Annals of Internal Medicine (2010)

ACP Journal Club21 December 2010Population-based screening using prostate-specific antigen testing reduced prostate cancer mortalityRichard M. Hoffman, MD, MPHRichard M. Hoffman, MD, MPHNew Mexico VA Healthcare System, Albuquerque, New Mexico, USA (R.M.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-12-201012210-02009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHugosson J, Carlsson S, Aus G, et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Lancet Oncol. 2010:11:725-32. https://pubmed.ncbi.nlm.nih.gov/20598634Clinical Impact RatingsGIM/FP/GP: References1 Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-8. [PMID: 19297566] Google Scholar2 Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2005;352:1977-84. [PMID: 15888698] Google Scholar3 Draisma G, Etzioni R, Tsodikov A, et al. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst. 2009;101:374-83. [PMID: 19276453] Google Scholar4 Presti JC. Prostate biopsy: current status and limitations. Rev Urol. 2007;9:93-8. [PMID: 17934565] Google Scholar Author, Article, and Disclosure InformationAffiliations: New Mexico VA Healthcare System, Albuquerque, New Mexico, USA (R.M.H.)This article was published at Annals.org on 7 December 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 December 2010Volume 153, Issue 12Page: JC6-9KeywordsAntigensBiopsyCancer screeningProstate cancerResearch designRisk managementUltrasound imaging ePublished: 21 December 2010 Issue Published: 21 December 2010 CopyrightCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
STUDIES OF TWO KINDS OF VIRUS PARTICLES WHICH COMPRISE INFLUENZA A2 VIRUS STRAINS
Authors: Purnell W. Choppin, Igor Tamm
Journal: The Journal of Experimental Medicine (1960)

Inhibitors present in normal human and animal sera prevented hemagglutination by and neutralized infectivity of inhibitor-sensitive influenza A2 virus. Starch zone electrophoresis of sera indicated that the same serum components possess both hemagglutination-inhibiting and neutralizing activities. The greatest amount of inhibitory activity was found in normal horse serum, and the inhibitory activity increased with heating or treatment with concentrated solutions of urea. The inhibitory activities on human, ferret, and rabbit sera were markedly reduced but not completely eliminated by V. cholerae filtrate and purified neuraminidase. The inhibitory activity of horse serum was only moderately reduced by these agents. The nature of the horse serum inhibitor and the differences in the interactions of inhibitor-sensitive and insensitive influenza A2 virus particles and pre-1957 influenza viruses with receptors have been discussed.
Abstract 1138: Breast cancer-derived mutations abolish Na+/H+ exchanger regulatory factor 1 inhibition of platelet-derived growth factor signaling
Authors: Shan Cheng, Yang Li, Duiping Feng, Ying Yang, Longyan Yang, Yunying Zhou, Ying Xiong, Licui Sun, Wenguo Jiang, Junqi He
Journal: Cancer Research (2011)

Abstract Na+/H+ exchanger regulatory factor 1 (NHERF1, also known as EBP50) is a scaffold protein known to interact with a number of target proteins, including cancer-related proteins such as phosphatase and tensin homolog deleted on chromosome 10 (PTEN), neurofibromatosis 2, spleen tyrosine kinase, platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and β-catenin. This suggests a possible function of NHERF1 as a negative tumor regulator. Several lines of evidence have suggested that NHERF1 is involved in carcinogenesis. However, the mechanisms by which NHERF1 plays a role in breast cancer have not yet been clearly defined. Three point mutations in nherf1 (K172N, R180W, and D301V) were recently identified in breast cancer cell lines or primary breast tumors. To gain more insight into the functional properties of NHERF1, wild-type (wt) and cancer-derived nherf1 mutations were introduced into a human non-small cell lung cancer cell line, SKMES-1. NHERF1-wt overexpression suppressed the malignant phenotypic characteristics of SKMES-1 cells, including cell proliferation, migration, and invasion. Three nherf1 mutations led to complete or partial loss of NHERF1 functions by affecting the formation of PTEN/NHERF1/PDGFRβ complex, attenuating NHERF1-mediated inhibition of PDGF-induced AKT and ERK activation, and abolishing the tumor suppressor effects mediated by NHERF1-wt. These results provide the first evidence of the functional consequences and signaling properties of breast cancer-derived nherf1 mutations, and suggest that these nherf1 mutations might play a causal role in tumor development and progression. 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 1138. doi:10.1158/1538-7445.AM2011-1138
Factors influencing vascular hyporesponsiveness to angiotensin II.
Authors: R Adamick, M E Gold, S Hayes, R Coleman, J T McCreary, S Sabatini, J A Arruda, N A Kurtzman
Journal: Circulation Research (1981)

Bartter's syndrome is characterized, in part, by hyporesponsiveness to the pressor effect of exogenous angiotensin II (AII). This has been attributed to volume contraction, hypokalemia, and/or increased prostaglandin (PG) levels. In order to investigate factors responsible for a diminished response to the pressor effect of AII, rats were made hypokalemic or volume contracted and hypokalemic (VCHK) by dietary restriction. AII sensitivity was examined by determining the dose of AII required to raise the mean arterial pressure 20 mm Hg. When compared with control rats. VCHK and hypokalemic rats were significantly less sensitive to AII. VCHK rats were significantly less sensitive to AII than hypokalemic rats. Both experimental groups were similarly hypokalemic, but plasma renin activity (PRA) of VCHK only was greater than control values. In VCHK rats, acute K+ restoration partially corrected AII hyporesponsiveness, although plasma K+ increased to normal. In VCHK rats, acute volume expansion with normal saline similarly achieved only partial correction of AII hyporesponsiveness although PRA values fell to the control range. Simultaneous K+ restoration and volume expansion to VCHK rats successfully restored AII sensitivity to the control range. Dietary sodium, chloride, and potassium restriction did not increase urinary excretion to PGE2. Indomethacin (5 mg/kg, iv) given acutely to VCHK rats did not significantly after baseline hyporesponsiveness to AII. Norepinephrine vascular sensitivity was not affected by either volume contraction or hypokalemia. These data demonstrate that volume contraction and hypokalemia individually depress exogenous AII sensitivity in the rat and do so by separate and additive mechanisms. Furthermore, these mechanisms appear to be independent of PG.
DESCENT OF THE TESTICLE IN ADULT LIFE.
Authors: ALBERT H. TUTTLE
Journal: JAMA (1894)

As such cases as the following must be of extreme rarity, and as they shed a great amount of light on the phenomena of earlier and normal descent, and at the same time perhaps instruct us somewhat as to the manner in which we should deal with cases of undescended testicle; cases where the majority of opinion has been in favor of the complete removal of the organ when it interferes with the comfort of the patient, is caught in the inguinal rings, or complicates a hernia, I have deemed this instance one worthy of consideration. Not long ago I operated for strangulated hernia complicated with undescended testicle, and after closing the hernial sac and rings, drew the testicle, which was enclosed in the sac, into the scrotum and fastened it there with the tunica by means of stitches. This procedure necessitated the invagination in part of the scrotum. The
Controlling Type 2 Diabetes Are the Benefits Worth the Costs?
Authors: John A. Colwell
Journal: JAMA (1997)

Ever since the publication of the Diabetes Control and Complications Trial,<sup>1</sup>health care professionals, people with diabetes, administrators, and governmental agencies have been concerned about translation of the findings into clinical practice. The study showed that an intensive approach to glycemic regulation, which entailed frequent visits and contact with a health care team, can produce a significant improvement in hemoglobin A1c (HbA<sub>1c</sub>) levels in people with type 1 diabetes, and can lower the risk for progression of retinopathy from 50% to 75%, depending on the end points chosen. In addition, significant lowering of the risk for progression of albuminuria and sensory neuropathy was achieved. Some of the major issues have been: 1. Should these results be applied to people with type 2 diabetes? 2. What are the guidelines for levels of HbA<sub>1c</sub>that should lead to action, and what is the target level to achieve? 3. Can
Synthetic Retinoids for the Secondary Prevention of Hepatocellular Carcinoma
Authors: David A. Shafritz
Journal: New England Journal of Medicine (1996)

In this issue of the Journal, Muto et al.1 report a decrease in the incidence of second primary hepatocellular carcinomas in patients treated with polyprenoic acid, an acyclic retinoid, after the resection or ethanol ablation of small, solitary primary hepatocellular carcinomas. The rationale for this clinical trial was based on studies in animal models of hepatocarcinogenesis and hepatoma cell lines, which suggested that polyprenoic acid inhibits chemically induced or spontaneous hepatocarcinogenesis and suppresses cell growth and the production of alpha-fetoprotein in human hepatoma cell lines. Muto and colleagues, who have been studying retinoid derivatives for more than a decade, have . . .
Comparative Safety of Endovascular Aortic Aneurysm Repair Over Open Repair Using Patient Safety Indicators During Adoption
Authors: John Rose, Christopher Evans, Andrew Barleben, Dennis Bandyk, S. Eric Wilson, David C. Chang, John Lane
Journal: JAMA Surgery (2014)

<h3>Importance</h3> In 2003, the Agency for Healthcare Research and Quality established Patient Safety Indicators (PSIs) to monitor preventable adverse events during hospitalizations. <h3>Objective</h3> To evaluate the comparative safety of endovascular aneurysm repair (EVAR) vs open aneurysm repair (OAR) of abdominal aortic aneurysm by measuring PSIs associated with each procedure over time. <h3>Design, Setting, and Participants</h3> Cases of abdominal aortic aneurysm repair were extracted from the Nationwide Inpatient Sample (2003-2010). Patient Safety Indicators were calculated using Agency for Healthcare Research and Quality software (Win QI, version 4.4). Unadjusted analysis included year, age, sex, race/ethnicity, comorbidities, rupture status, hospital teaching status, and emergency status. Multivariable analysis was stratified by year for any PSI in EVAR vs OAR. Postoperative mortality was analyzed to control for the overall safety. <h3>Main Outcomes and Measures</h3> Patient Safety Indicators and mortality. <h3>Results</h3> In total, 43 385 EVARs and 27 561 OARs were documented, with 1289 (3.0%) and 3094 (11.2%) associated PSIs, respectively. Compared with those receiving OAR, patients receiving EVAR were more likely to be male, older, and of white race/ethnicity; have a lower Charlson Comorbidity Index; and seek care at teaching hospitals (<i>P</i> &lt; .001 for all). Patients were less likely to have a PSI after EVAR than after OAR. Overall, multivariable analysis showed that EVAR was associated with a 42.1% decrease in the risk-adjusted odds of any PSI compared with OAR (odds ratio, 0.58; 95% CI, 0.51-0.65). Stratified by year, the risk-adjusted odds of any PSI after EVAR were comparatively less likely than after OAR every year except for 2007, and the odds of death were comparatively less every year. The annual percentage of PSIs among all aortic repairs decreased from 7.4% in 2003 to 4.4% in 2010, while the proportion of total repairs that were EVARs increased from 41.1% in 2003 to 75.3% in 2010. <h3>Conclusions and Relevance</h3> Patient Safety Indicators can be used to monitor the comparative safety of emerging surgical technologies. Herein, EVAR was safer than OAR. The adoption of minimally invasive technology can improve safety among surgical admissions.
Outcome of Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting
Authors: Graham S. Hillis, Kenton J. Zehr, Amy W. Williams, Hartzell V. Schaff, Thomas A. Orzulak, Richard C. Daly, Charles J. Mullany, Richard J. Rodeheffer, Jae K. Oh
Journal: Circulation (2006)

Background— There are few data regarding medium-term outcome of coronary artery bypass grafting (CABG) in patients with severe left ventricular (LV) systolic dysfunction, particularly in the modern era, and even less assessing preoperative factors that might identify patients at highest risk. Methods and Results— Three hundred seventy-nine consecutive patients with LV ejection fraction ≤35%, who underwent isolated first CABG between 1995 and 1999 were studied. Potential preoperative and perioperative predictors of outcome were recorded and patients followed-up for a median of 3.8 years. The primary study end-point was all-cause mortality. The 30-day, 1-year, and 3-year survival rates were 94.5%, 88%, and 81%, respectively. The independent predictors of mortality were preoperative estimated glomerular filtration rate (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97 to 0.99 per mL/min/1.73m 2 ; P &lt;0.001) and age (HR, 1.03; 95% CI, 1.01 to 1.06 per year; P =0.005). Conclusions— Patients with significant LV systolic dysfunction undergoing isolated CABG using contemporary techniques have a good medium-term survival. Renal dysfunction is the strongest independent predictor of mortality.
Limb Blood Flow During Exercise Is Dependent on Nitric Oxide
Authors: Andrew J. Maxwell, Eric Schauble, Daniel Bernstein, John P. Cooke
Journal: Circulation (1998)

Background —We have recently reported that hypercholesterolemia reduces aerobic exercise capacity in mice and that this is associated with a reduced endothelium-dependent vasodilator function, endothelium-derived nitric oxide (EDNO) production, and urinary nitrate excretion. These findings led us to test the hypothesis that EDNO production contributes significantly to limb blood flow during exercise and to determine whether loss of EDNO production is responsible for the decline in exercise capacity observed in hypercholesterolemia. Methods and Results —Twelve-week-old wild-type (E + ; n=9) and apoE-deficient (E − ; n=9) C57BL/6J mice were treadmill-tested to measure indices defining exercise capacity on a metabolic chamber–enclosed treadmill capable of measuring oxygen uptake and carbon dioxide excretion. Urine was collected before and after treadmill exercise for determination of vascular NO production assessed by urinary nitrate excretion. The wild-type mice were then given nitro- l- arginine (E + LNA) in the drinking water (6 mg/dL) for 4 days before undergoing a second treadmill testing and urinary nitrate measurement. An additional set of 12-week-old wild-type mice was divided into 2 groups: 1 receiving regular water (E + ; n=8) and 1 administered LNA for 4 days (E + LNA; n=8). These mice, along with an additional set of E − mice (n=8), underwent treadmill testing to determine maximal oxygen uptake (V̇ o 2 max). The mice were then cannulated such that the tip of the tubing was positioned in the ascending aorta. Fluorescent microspheres (20 000) were infused into the carotid cannula while the mice were sedentary and again while approaching V̇ o 2 max. When the mice were euthanized, the running muscles were collected and fluorescence intensity was measured to determine the peak-exercise redistribution of blood flow to the running muscles (expressed as percentage of total cardiac output, %COrm) during both states. Both E + LNA and E − mice demonstrated a markedly reduced postexercise urinary nitrate excretion, aerobic capacity, and %COrm at V̇ o 2 max compared with E + . Conclusions —EDNO contributes significantly to limb blood flow during exercise. Conditions that reduce EDNO production disturb the hyperemic response to exercise, resulting in a reduced exercise capacity.
Decreased muscle strength in patients with alcoholic liver cirrhosis in relation to nutritional status, alcohol abstinence, liver function, and neuropathy
Authors: Henning Andersen, Mette Borre, Johannes Jakobsen, Per Heden Andersen, Hendrik Vilstrup
Journal: Hepatology (1998)

To study motor function quantitatively in alcoholic liver cirrhosis muscle strength, liver function, peripheral nerve function, and nutrition were assessed in 24 patients. Isokinetic strength of flexion and extension at elbow, wrist, hip, knee, and ankle and of shoulder abduction and adduction was evaluated and compared with findings in 24 matched healthy subjects. Degree of liver disease was assessed with the Child-Pugh score and the galactose elimination capacity (GEC). Nutritional status was evaluated with an estimation of lean body mass (LBM) from 24-hour urinary creatinine excretions. Peripheral nerve function was evaluated with neurological symptom and disability scores, nerve conduction studies, and quantitative sensory tests summed to obtain a neuropathy rank-sum score (NRSS) for each patient. Combined muscle strength at hip, knee, ankle, shoulder, elbow, and wrist were weakened with 34% (P < .005), 35% (P < .001), 35% (P < .01), 34% (P < .01), 29% (P < .01), and 29% (P < .02), respectively. The median Child-Pugh score was 7 (range, 5-12), and the median duration of alcohol abstinence was 90 days (range, 5-960 days). After multiple linear regression analysis including LBM, Child-Pugh score, GEC, duration of alcohol abstinence, and NRSS, only LBM was correlated to the strength at the knee (r=.79; P < .0001) and at the ankle (r=.63; P < .01). It is concluded that muscle strength is weakened substantially in alcoholic patients with liver cirrhosis and that weakness is related to the severity of malnutrition but not to the severity of liver disease, duration of alcohol abstinence, or neuropathy.
Prominent celecoxib researcher admits fabricating data in 21 articles
Authors: J. Lenzer
Journal: BMJ (2009)

A well known researcher who promoted the use of the non-steroidal anti-inflammatory drug celecoxib has admitted fabricating data in 21 of his 72 articles indexed by PubMed. The case is “among the biggest which has come to light,” said Harvey Marcovitch, chairman of the Committee on Publication Ethics, an international forum for publishers and editors of peer reviewed journals.

Scott S Reuben, chief of the acute pain service at Baystate Medical Center in Springfield, Massachusetts, has admitted the fraud, says a notice issued by the centre in late January. 

Jane Albert, a spokeswoman for the centre, a teaching hospital that serves as a campus of Tufts University School of Medicine, said that after evaluating the 51 other articles by Dr …