tbuckley/cabot-search huggingface dataset:
Abstract 2063: Synergistic anticancer activity of Sorafenib in combination with HS-173, a novel PI3K inhibitor against pancreatic cancer cells.
Authors: Sun-Mi Yun, Kyung Hee Jung, Hyunseung Lee, Byung Hee Park, Hong Hua Yan, Soon-Sun Hong
Journal: Cancer Research (2013)

Abstract The K-RAS mutation, resulting in activation of the Raf/MEK/ERK pathway, has been implicated in pancreatic cancer development. And the PI3K/Akt pathway is highly activated in pancreatic cancer and considered to be a cancer hallmark. The principal objective of this study was to assess the synergic effect between Sorafenib (a Raf inhibitor) and HS-173 (a novel PI3K inhibitor) along with the underlying mechanism to gain insight into novel therapeutic strategies for treating pancreatic cancer. We first investigated the cytotoxic effect of co-treatment with Sorafenib and HS-173 using the Calcusyn program. Combined treatment with the two drugs synergistically inhibited the viability of Panc-1 cells (combination index &amp;lt; 1). Concomitantly, co-treatment with Sorafenib and HS-173 induced G2/M arrest and increased apoptosis with the loss of mitochondria potential. Apoptosis resulting from co-treatment with Sorafenib and HS-173 was accompanied by increased levels of cleaved caspase-3 and PARP as well as greater numbers of TUNEL-positive apoptotic cells compared to treatment with either drug alone. Furthermore, combined treatment with these drugs decreased the expression HIF-1α and VEGF, two factors that play an important role in angiogenesis. The anti-angiogenic effect of simultaneous treatment with Sorafenib and HS-173 was confirmed by observing the suppressed tube formation of VEGF-induced human umbilical vein endothelial cells and inhibition of blood vessel formation in a Matrigel plug assay in mice. Taken together, our study demonstrated that combined treatment with Sorafenib and HS-173 has a synergistic anticancer effect on pancreatic cancer cells, indicating that simultaneously targeting the Raf/MEK and PI3K/Akt pathways can induce a synergistic inhibitory effect on pancreatic cancers in which both pathways are activated. Based on the observations from our study, we suggest that the combined administration of these two drugs may be considered to be a new therapeutic regimen for treating pancreatic cancer. Citation Format: Sun-Mi Yun, Kyung Hee Jung, Hyunseung Lee, Byung Hee Park, Hong Hua Yan, Soon-Sun Hong. Synergistic anticancer activity of Sorafenib in combination with HS-173, a novel PI3K inhibitor against pancreatic cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2063. doi:10.1158/1538-7445.AM2013-2063
Clinical utility of two-dimensional Doppler echocardiographic techniques for estimating pulmonary to systemic blood flow ratios in children with left to right shunting atrial septal defect, ventricular septal defect or patent ductus arteriosus
Authors: Jesus Vargas Barron, David J. Sahn, Lilliam M. Valdes-Cruz, Carlos Oliveira Lima, Stanley J. Goldberg, Ehud Grenadier, Hugh D. Allen
Journal: Journal of the American College of Cardiology (1984)
Endotoxin induces structure-function alterations of rat liver peroxisomes: Kupffer cells released factors as possible modulators
Authors: Miguel A. Contreras, Mushfiquddin Khan, Brian T. Smith, Anna M. Cimini, Anne G. Gilg, John Orak, Inderjit Singh, Avtar K. Singh
Journal: Hepatology (2000)

We report that endotoxin treatment results in decreased amounts of peroxisomes as well as changes in structure and function of peroxisomal membranes. Peroxisomes isolated from the liver of control and treated animals showed a marked decrease in total protein, but no significant alteration in the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) protein profile. However, the Western blot study of the peroxisomal β-oxidation enzymes and catalase showed an increase in those enzymes in the peroxisomal peak of normal density in endotoxin-treated rats. Disintegration of peroxisomal membranes by carbonate treatment from endotoxin-treated liver and change in the fluidity of peroxisomal membranes suggests alterations in peroxisomal membrane structure. No such alterations were found in mitochondrial or microsomal membranes of endotoxin-treated livers. The lipid analysis of these organelles showed that the only organelle affected was the peroxisome, with a significant decrease in the phospholipid and cholesterol concentrations. To understand the mechanism of endotoxin-mediated alterations in peroxisomes, we studied the possible role of Kupffer cell secreted soluble factors (tumor necrosis factor α [TNF-α]) on the peroxisomal structure/function. Inactivation/elimination of Kupffer cells by gadolinium chloride before endotoxin treatment did not normalize the overall peroxisomal protein amount and the lipid composition of isolated peroxisomes. However, the levels of individual protein amount in remaining peroxisomes were normalized. Endotoxin also decreased peroxisomal β-oxidation, and this was partially restored with gadolinium treatment. These results clearly show that peroxisomes are severely affected by endotoxin treatment and suggest that the damage to this organelle may contribute, at least in part, to endotoxin-induced hepatic cytotoxicity.
Letter: Incomprehensible explanations.
Authors: J Couper-Smartt
Journal: BMJ (1973)

<h3>Introduction</h3> Liver biopsy (LB) can be associated with adverse outcomes including technical failures, complications and inadequate tissue for histological analysis. The indication for a chosen route of LB is variable between physicians and the impact of the chosen route of LB is often unclear. <h3>Method</h3> Retrospective review of all LB performed at a UK transplant centre over a 12 month period focussing on indication and route of LB, complications, histological adequacy and variability in operator specialty and experience. <h3>Results</h3> Over the 12 month period 570 LB were performed, of which 330 were transjugular liver biopsies (TJLB) and 240 were percutaneous liver biopsies (PCLB). A LB was categorised as being histologically adequate if a histological diagnosis could be made, or if the sample met the histological standard in the literature (a 15 mm sample, with 6 or more complete portal tracts). Overall, 94% of LB were adequate based on the histological standard, and 98% allowed histological diagnosis. There were no significant differences in adequacy when comparing TJLB vs. PCLB route; however, a consultant radiologist was more likely to provide an adequate sample than a radiology registrar (p = 0.02). The overall complication rate for a liver biopsy was 5.6%. This included 8 major complications (1.4%) and 24 minor complications (4.2%). Neither the route of LB (TJLB vs. PCLB) or operator (consultant radiologist vs. radiology registrar vs. hepatologist) was significantly associated with the development of a complication. The technical failure rate of a TJLB was 4%; these included failure to puncture internal jugular vein, failure to cannulate the hepatic vein, or an unstable sheath position. There were no technical failures in the PCLB group. Screening time for a TJLB was significantly longer if the procedure was done by a radiology registrar when compared to both a hepatologist (p = 0.01) or consultant radiologist (p = 0.003). Apart from the standard indications for a TJLB we found a patient was significantly more likely to undergo a TJLB if they were post-transplant compared to pre-transplant (p = 0.001) and if the biopsy was deemed an emergency compared to an elective procedure (p = 0.001). In our cohort we identified 130 patients who had a TJLB with no indication for this procedure. <h3>Conclusion</h3> We have demonstarted that TJLB and PCLB have no significant differences in complication rates or adequacy of histological sample. Technical failure is more common in TJLB compared to PCLB. A TJLB is our preferred method in emergency cases and post-transplant patients. Further information regarding cost and patient experience is needed to identify if a change in practice is indicated. <h3>Disclosure of interest</h3> None Declared.
Double-balloon enteroscopy for diagnosis of Meckel’s diverticulum in a patient with gastrointestinal bleeding
Authors: Y. Nakashima, I. Nakamura, H. Miyatani, Y. Yoshida, F. Konishi, S. Yamada
Journal: Endoscopy (2007)

A 27-year-old woman presented with a history of gastrointestinal bleeding. Her medical history was otherwise unremarkable. Esophagogastroduodenoscopy and colonoscopy of the terminal ileum were carried out after an episode of gastrointestinal bleeding, but the source of the bleeding remained unidentified. Double-balloon endoscopy of the small intestine [1] was then conducted via the anal approach. Examination of the distal ileum disclosed a diverticulum with an ulceration at about 50 cm proximal to the ileocecal valve (Figure [1]). Radiography showed a diverticulum 6 cm long in the ileum (Figure [2]). Biopsy specimens from the diverticulum revealed gastric mucosa (Figure [3]). The ulcer was thought to be caused by ectopic gastric mucosa.
Progression of liver fibrosis in post-transplant hepatitis C: Mechanisms, assessment and treatment
Authors: Marina Berenguer, Detlef Schuppan
Journal: Journal of Hepatology (2012)

Liver fibrosis results from an excessive wound healing response in most chronic liver diseases, such as hepatitis C. Despite great advances in antiviral therapy in recent years, progressive liver fibrosis remains a major problem for patients with recurrent hepatitis C after liver transplantation. Liver biopsy remains a central tool in the management of HCV-positive liver transplant recipients, but reliable non-invasive methods for the assessment of liver fibrosis, such as ultrasound elastography, are increasingly being incorporated in the management of post-transplant patients, helping predict prognosis, guide treatment decisions, and stratify patients for emerging antifibrotic therapies. In this manuscript, we will review the natural history as well as tools to monitor fibrosis progression in the HCV-positive liver transplant recipient, the mechanisms underlying rapid fibrosis progression in up to 30% of these patients, the effect of antiviral therapies and highlight promising antifibrotic approaches.
From Hippocrates to Virchow: Reflections on Human Disease
Authors: Roger J. Bulger
Journal: JAMA (1988)

This is a scholarly, readable, and provocative book that may interest students of medicine at all levels, including the most adroit masters of our art. Collected, ordered, and placed within a clearly written and brief text by a pathologist from the University of Arizona, the book offers glimpses into the views and philosophies of many of the great minds throughout the history of Western civilization. Each passage is brief and can be easily passed over, if for one reason or another it does not interest the reader, without fear of changing the impact of the next piece. There are several positive outcomes from reading this little book. First, there are a number of useful and striking items, although what strikes one reader may not be the favorite of the next. Second, the glimpses into the paradigms of the past and their great variety should give pause at the transitory nature
Predicted declines in sickle allele frequency in Jamaica using empirical data
Authors: N.A. Hanchard, I. Hambleton, R.M. Harding, C.A. McKenzie
Journal: American Journal of Hematology (2006)

The high frequency of the sickle allele in some parts of Africa is understood to be a consequence of high malarial endemicity. One corollary of this is that the sickle allele frequency should be declining in populations of African ancestry that are no longer exposed to malaria. We have previously shown that there has been no change in sickle allele frequency in malaria-free Jamaica between two large-scale neonatal screening exercises conducted in 1973–1981 and 1995–2003. To evaluate the determinants of, and derive expected values for, sickle allele frequency in Jamaica, local empirical data were used to estimate the parameters of deterministic models of allele frequency decline. We found that although model predictions were broadly consistent with observed values in the 1973–1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction. Close agreement between predicted and observed values was only achieved by simulating a recent, marked increase in HbSS fitness. Thus, the “unexpected” persistence of the sickle allele in Jamaica may reflect the fact that the actual fitness among SS individuals is higher than that previously realized. If true, our models suggest that without substantial changes in current screening and counseling practice, there will be little “natural” reduction in sickle allele frequency for several hundred years. Better estimates of relative fitness will be helpful in refining these predictions and may aid in assigning health care priorities in Jamaica and the African Diaspora. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc.
AN UNUSUAL CASE OF FRACTURE-DISLOCATION OF THE FEMUR
Authors: George R. Harris
Journal: JAMA (1924)

D. H., a boy, aged 9, was running over heavily crusted snow, when he broke through and fell forward. Another boy, who was running close after him, fell over him. The patient was unable to arise, and was carried home. When seen four hours later, the right leg was in eversion and partial flexion. The head of the femur was felt over the obturator foramen, and, on the slight motion possible, crepitus was felt. The fracture was at the junction of the middle and upper thirds of the femur. The next day, under chloroform anesthesia, reduction of the dislocation was accomplished, and the leg was put in extension with adhesive strips; a weight of about 10 pounds was then placed over the end of the bed. The right leg measured 25½ inches (64.7 cm.), and the left, 27 inches (68.5 cm.), measuring from the anterior superior spine of the ilium
THE ELECTRICAL TREATMENT OF FIBROID TUMORS.Read in the Section of Obstetrics and Diseases of Women, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May 5-8, 1891.
Authors: G. BETTON MASSEY
Journal: JAMA (1891)

The progress of the Apostoli method of treating fibroid tumors of the uterus, presents both analogies and contrasts to those of some of the recent therapeutic claims that have been widely investigated by the medical world. Recognized at last, owing to the persistent agitation of its originator, it was, like the Brown-Séquard and Koch theories, enthusiastically adopted by those pioneer advocates who often make up for crudeness of training, and inexactness of observation, by a debt of stimulated progress laid upon subsequent workers. In contrast to the theories alluded to, it has since borne the test of capable experiment to an extent that even exceeds the original claims, and with the broadened use of electricity in other allied conditions, has made a new departure in gynecology. Unlike them also, it has encountered an opposition of unparalleled fierceness, an opposition, however, that has been as healthy as it has been fierce.
A memorable patient: A chandelier and a vat of custard
Authors: K. Whybrew
Journal: BMJ (2001)

It was a busy Friday night in casualty. We were one senior house officer down and there had been a major accident on a nearby main road. All of us had been looking after seriously injured patients for the preceding couple of hours—not all of them had survived, and emotions were running high. During that time, the backlog of minor injuries had built up to a six hour wait, and tempers were fraying …
alpha6beta4 integrin abnormalities in junctional epidermolysis bullosa with pyloric atresia
Authors: G.H.S. Ashton, P. Sorelli, J.E. Mellerio, F.M. Keane, R.A.J. Eady, J.A. Mcgrath
Journal: British Journal of Dermatology (2001)

Journal Article α6β4 integrin abnormalities in junctional epidermolysis bullosa with pyloric atresia Get access G.H.S. Ashton, G.H.S. Ashton Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar P. Sorelli, P. Sorelli Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.E. Mellerio, J.E. Mellerio Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar F.M. Keane, F.M. Keane Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.A.J. Eady, R.A.J. Eady Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.A. Mcgrath J.A. Mcgrath Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Dr John McGrath. E‐mail: john.mcgrath@kcl.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 2, 1 February 2001, Pages 408–414, https://doi.org/10.1046/j.1365-2133.2001.04038.x Published: 01 February 2001
Duty and Healing: Foundations of a Jewish Bioethic.
Authors: Paul Root Wolpe
Journal: JAMA (1996)

Bioethicists often draw upon the common philosophical and legal traditions that form the foundation of Western moral reasoning to formulate their arguments, However, bioethicists who also draw from a particular regligious tradition bring to their arguments texts, authorities, or discourses that may not be deemed authoritative by their audience. Add to that the tradition of the separation of church and state, and religiously based bioethicists face a communicative dilemma: moral stances arrived at through parochial religious interpretive processes must be defended in public using generally accepted secular concepts and justifications. Much can get lost in the translation. In Benjamin Freedman's superb book,<i>Duty and Healing: Foundations of a Jewish Bioethic</i>, Freedman seamlessly integrates the Jewish textual underpinnings of his moral position with his duties as a clinical bioethicist in a Montreal, Quebec, hospital.
Bell Palsy and Herpes Simplex Virus
Authors: P.P. Devriese
Journal: Annals of Internal Medicine (1996)

Letters15 October 1996Bell Palsy and Herpes Simplex VirusP.P. Devriese, MD, PhDP.P. Devriese, MD, PhDAcademic Medical Center, 1105 AZ Amsterdam, the NetherlandsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-8-199610150-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Murakami and colleagues [1] used polymerase chain reaction to detect herpes simplex virus type 1 (HSV-1) DNA in patients with Bell palsy and to detect varicella-zoster DNA in patients with the Ramsay Hunt syndrome. Their report is an important contribution to the etiology of these diseases [2].Contrary to the authors' statement in the introduction of their article, I suggested ischemia not as a cause of Bell palsy but as a factor in the pathogenesis of the paralysis. Inflammation of the facial nerve caused by reactivation of the virus may provoke edema and, as a result, compress ...References1. Murakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell palsy and herpes simplex virus: identification of viral DNA in endoneurial fluid and muscle. Ann Intern Med. 1996; 124:27-30. Google Scholar2. Baringer JR. Herpes simplex virus and Bell palsy [Editorial]. Ann Intern Med. 1996; 124:63-5. Google Scholar3. Devriese PP. Compression and ischaemia of the facial nerve. Acta Otolaryngol (Stockholm). 1974; 77:108-18. Google Scholar4. Hunt JR. On herpetic inflammations of the geniculate ganglion. A new syndrome and its complications. J Nerv Ment Dis. 1907; 34:73-96. Google Scholar5. Devriese PP. Facial paralysis in cephalic herpes zoster. Ann Otol Rhinol Laryngol. 1968; 77:1101-9. Google Scholar Author, Article, and Disclosure InformationAffiliations: Academic Medical Center, 1105 AZ Amsterdam, the Netherlands PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByProtective effects of edaravone against ischemia-induced facial palsy 15 October 1996Volume 125, Issue 8Page: 698KeywordsDNAEtiologyFacial nerveHerpes simplexInflammationIschemiaNervesParalysisPathogenesisPolymerase chain reaction Issue Published: 15 October 1996 CopyrightCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...