tbuckley/cabot-search huggingface dataset:
Abstract 4607: Stathmin is involved in the maternal embryonic leucine zipper kinase pathway and impacts in the outcome of glioblastoma
Authors: Miyuki Uno, Sueli Mieko Oba-Shinjo, Roseli Silva, Marcela Gimenez, Jose Cesar Rosa, Suely Kazue Nagahashi Marie
Journal: Cancer Research (2014)

Abstract INTRODUCTION: Maternal Embryonic Leucine Zipper Kinase (MELK) is a serine/threonine kinase involved in several cell processes, including the cell cycle, differentiation, proliferation, and apoptosis. MELK has also shown multiple features consistent with the potential utility as an anticancer target, including in astrocytomas. However, the detailed downstream signaling pathway of MELK in cancer cells is still not fully understood and the putative role of MELK in astrocytomas remains unclear. The discovery of proteins involved in the MELK pathway might be important to develop additional small molecular compound to improve effectiveness. PURPOSE: This study aim to analyze proteins and/or genes involved in the MELK pathway in the tumorigenesis of gliomas. MATERIAL AND METHODS: Analysis of the expression profile of a panel of protein relevant to the process of tumorigenesis that MELK is involved was performed by Proteomic analysis by two dimensional electrophoresis and mass spectrometry for human glioma cell line U87MG transfected with siRNA for the MELK compared to U87MG transfected with non-target control (NTC) cells. Analysis and validation of gene expression was performed by Quantitative real time PCR (qRT-PCR) using SYBR Green method in a series of 153 astrocytomas of different malignant grade (23 AGI, 26 AGII, 18 AGIII and 86 AGIV or glioblastoma - GBM) and 22 non neoplastic (NN) brain samples. RESULTS: We identified Stathmin/oncoprotein 18 (STMN1) involved in the cell cycle, as one of twelve proteins differentially expressed, with lower expression when MELK was silenced. A significant higher expression of STMN1 in malignant diffusely infiltrative astrocytomas when compared to non-invasive pilocytic astrocytoma was found (p&amp;lt;0.0001). Strong correlation for MELK and STMN1 associated expression was observed (r=0.741, p&amp;lt;0.0001) in GBM. STMN1 hyperexpression alone impacted at GBM outcome with an overall survival of 5.4 months in contrast to 13.4 months when both genes were hypoexpressed (log rank=0.002). CONCLUSIONS: Thus, our results showed that STMN1 is downstream in the MELK pathway and might play an important role in astrocytoma tumorigenesis. Citation Format: Miyuki Uno, Sueli Mieko Oba-Shinjo, Roseli Silva, Marcela Gimenez, Jose Cesar Rosa, Suely Kazue Nagahashi Marie. Stathmin is involved in the maternal embryonic leucine zipper kinase pathway and impacts in the outcome of glioblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4607. doi:10.1158/1538-7445.AM2014-4607
On the Action of Cannabis Indica
Authors: J. Oliver
Journal: BMJ (1883)

ItIhe' izaWination (mode IbrMr.Roos, curator) showed that the gtngrencous patohes upon thea abdomen had,pewetrated the entire thicknessof t!the skin, exposisig the musdles beneath; in other parts, the uloration was: oi lessJidepth.lIt each lung ,there were.several small recent secondary: abscesses, surrounded by a zone of hyperzmic tissue; otnthe left side.there was also recent lymph on the suarface of' -the' pleura, and two ounces of purulent fluid ^n its cavity.A careful inspection of the brain, the other viscera, and the joints, revealed nothing unnatural.-In this case the diagnosis was ,made certain by the child having been seen by: a competent 'observer, with the'prdinary eruption of varicella before gangrene had commenqed.But to any one acquainted with Mr. Hutchinson's paper, the history and: aspect 6f the 'eruption made the nature of the case sufficiently apparent.f;'The gangcr,ene in this instance set in suddenly arfd 'iogressod with grqat rapidity; ansi a point of interest is the early-occurrence 'of pyemia, which was no doubt the immediate cause of death.I am'afraid.the case does not throw any light upon the cause of this serioa'oomplication of what is usually a trifling disease.This child was very ill-npuxished (probably from wrong feeding) and feeble, but other recorded' itstances of tho disease have occurred in healthy children. PEPTONES IN URINE.
Guidelines could reduce childrens head injuries from cycling
Authors: A. Ellis
Journal: BMJ (2002)

A set of guidelines to get cycle helmets on children's heads was launched last week by the charity the Bicycle Helmet Initiative Trust, with the support of transport minister David Jamieson.

The guidelines are the result of a three year initiative in Reading, in which helmet programmes were run in the community, linked to healthcare trusts. Helmet use among …
Synergistic Hemodynamic Effects of Low-dose Endotoxin and Acute Lung Injury
Authors: RENÉ GUST, JAMES KOZLOWSKI, ALAN H. STEPHENSON, DANIEL P. SCHUSTER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We evaluated the effects of low-dose endotoxin (15 microg/kg) on the pulmonary and systemic responses to oleic acid (OA)-induced acute lung injury in dogs. Animals given endotoxin alone (n = 5) showed a modest decrease in arterial blood pressure, but no effects on pulmonary hemodynamics, blood gases, cardiac output, or lung water accumulation. Animals (n = 6) given only OA (0.08 ml/kg) showed the expected development of mild-moderate pulmonary hypertension, a comparable reduction in arterial blood pressure, hypoxemia, increased lung water concentration, and an altered intrapulmonary perfusion pattern, as assessed by positron emission tomography. Animals (n = 7) given the same dose of endotoxin, followed 30 min later by the same dose of OA, developed a similar increase in lung water concentration as the group given OA alone, but failed to develop pulmonary hypertension or to redistribute pulmonary blood flow away from the edematous lung regions. In addition, arterial blood pressure fell significantly more than in the other groups. These responses were associated with a 30-fold increase in circulating prostacyclin (assayed as 6-keto prostaglandin F1 alpha [PGF1alpha]). The effects on systemic blood pressure, intrapulmonary blood flow redistribution, and eicosanoid production were eliminated by pretreating (n = 5) animals with meclofenamate (2 mg/kg). The results are consistent with a "priming" effect of low-dose endotoxin on the pulmonary endothelium, with exaggerated prostacyclin production in response to a subsequent lung injury. This interaction leads to altered intrapulmonary hemodynamics that exacerbate the development of hypoxemia, and to significant decreases in systemic blood pressure. To the extent that the lung is the most likely source of the increased prostacyclin production, the synergistic effects of low-dose endotoxin and lung injury may produce a kind of "lung shock."
A Manual of Cutaneous Medicine
Authors: Walter C. Lobitz
Journal: JAMA (1961)

These authors, having already succeeded in giving the student and practitioner of medicine a most complete text in dermatology, are again successful in offering this shorter, less expensive "manual." The authors clearly state their goals for this new volume in the preface: "To summarize—the chief useful facts regarding the diagnosis, prevention and cure of the diseases affecting the skin which are encountered frequently in daily practice.—To summarize those principles of physiology, chemistry and anatomy which are most useful in promoting an understanding of the genesis of dermatologic disease. To emphasize—those changes in the skin which may be representative of systemic disease. To hew to the line of as forthright and simple a terminology as possible.—To assess the true usefulness and the hazards—of treatment—. To indicate those diseases which may ordinarily be managed effectively in general practice, and those in which more specialized methods and experience may be essential. To substitute
Does prostacyclin enhance the selective pulmonary vasodilator effect of oxygen in children with congenital heart disease?
Authors: A Bush, C Busst, K Booth, W B Knight, E A Shinebourne
Journal: Circulation (1986)

We have obtained dose-response curves for the effects of prostacyclin on the pulmonary and systemic circulations in 20 children (median age 3 years) with pulmonary hypertension complicating congenital heart disease. Results were obtained with the children breathing both air and 100% oxygen. Under both sets of conditions, remote respiratory mass spectrometry was used to measure oxygen consumption and hence cardiac output by the direct Fick principle. When the subjects breathed air, prostacyclin caused a dose-dependent fall in pulmonary vascular resistance (measured in mm Hg . liter-1 . min . m2) (11.12 to 8.07, standard error of difference [SED] = 0.5, p less than .01). The level of the pulmonary vascular resistance when the subjects breathed air during the infusion of 20 ng/kg/min prostacyclin was not significantly different from that found when they breathed 100% oxygen and did not receive the drug (8.67 vs 8.93, SED = 0.55, p = NS). When infused while the subjects breathed 100% oxygen, prostacyclin caused additional dose-dependent pulmonary vasodilation (pulmonary vascular resistance 8.93 to 7.23, SED = 0.3, p less than .01). Unlike 100% oxygen, prostacyclin was not selective, and caused tachycardia and systemic hypotension at the higher doses. These results suggest that in children with congenital heart disease 100% oxygen does not maximally vasodilate the pulmonary circulation, and further pulmonary vasodilatation can be obtained with a blood-borne agent.
Liver biopsy in hepatitis C virus carriers with normal alanine aminotransferase levels
Authors: Laudio Puoti, Lia Bellis, Riccardo Guarisco
Journal: Hepatology (2009)

We read with great interest and enthusiasm the American Association for the Study of Liver Diseases position paper on liver biopsy.1 In this article, the authors give clear and flexible recommendations on when and how to do (or not to do) liver biopsy in everyday clinical practice. However, we would like to raise some doubts about the approach suggested for hepatitis C virus (HCV) carriers with normal alanine aminotransferase levels (ALT). Rockey et al. stated that "assessment of liver histology may be particularly beneficial in patients with human immunodeficiency virus and HCV who have persistently normal ALT levels, because these patients may have significant fibrosis". We believe that this approach is too restrictive, and that biopsy should be taken into consideration in all HCV carriers with normal ALT, regardless of human immunodeficiency virus (HIV) status. It is true that patients coinfected with HIV/HCV with normal ALT might suffer from more progressive fibrosis and more severe liver damage than carriers who are HIV-negative2; however, several studies have shown that the majority of HCV carriers with normal ALT have some degree of histological liver damage despite persistent biochemical normality,3 and that fewer than 20% of these people show normal liver (the true "healthy" HCV carriers).4 Although liver disease is usually minimal/mild and fibrosis is generally absent or minimal, the association of normal ALT with cirrhosis or with hepatocellular carcinoma has been reported,5, 6 even in the absence of HIV positivity. Thus, we believe that evaluation of liver fibrosis through biopsy might be very useful in this subset of patients with HCV, in particular when virologic or demographic features (e.g., unfavorable HCV types, advanced age, obesity, etc.) make it difficult to decide whether antiviral treatment should be offered.7 Laudio Puoti*, Lia Bellis*, Riccardo Guarisco*, * Department of Internal Medicine and Liver Unit, Marino General Hospital, Rome, Italy.
Abscess Mimicking Normal Spleen on ln-111 WBC Scan
Authors: DAVID H. SKLAR, CAROL S. MARCUS
Journal: Clinical Nuclear Medicine (1991)

A 38-year-old woman with unexplained fever underwent an In-111 WBC scan. Normal and near normal initial images were misleading because the patient had had a splenectomy for idiopathic thrombocytopenia purpura. Afterward, 200 cc of pus was drained from the abscess in the splenic bed.
Dual Inhibition of the PI3K/mTOR Pathway Increases Tumor Radiosensitivity by Normalizing Tumor Vasculature
Authors: Emmanouil Fokas, Jae Hong Im, Sally Hill, Sabira Yameen, Michael Stratford, John Beech, Wolfgang Hackl, Sauveur-Michel Maira, Eric J. Bernhard, W. Gillies McKenna, Ruth J. Muschel
Journal: Cancer Research (2011)

The aberrant vascular architecture of solid tumors results in hypoxia that limits the efficacy of radiotherapy. Vascular normalization using antiangiogenic agents has been proposed as a means to improve radiation therapy by enhancing tumor oxygenation, but only short-lived effects for this strategy have been reported so far. Here, we show that NVP-BEZ235, a dual inhibitor of phosphoinositide-3-kinase (PI3K) and mTOR, can improve tumor oxygenation and vascular structure over a prolonged period that achieves the aim of effective vascular normalization. Because PI3K inhibition can radiosensitize tumor cells themselves, our experimental design explicitly distinguished effects on the blood vasculature versus tumor cells. Drug administration coincident with radiation enhanced the delay in tumor growth without changing tumor oxygenation, establishing that radiosensitization is a component of the response. However, the enhanced growth delay was substantially greater after induction of vascular normalization, meaning that this treatment enhanced the tumoral radioresponse. Importantly, changes in vascular morphology persisted throughout the entire course of the experiment. Our findings indicated that targeting the PI3K/mTOR pathway can modulate the tumor microenvironment to induce a prolonged normalization of blood vessels. The substantial therapeutic gain observed after combination of NVP-BEZ235 with irradiation has conceptual implications for cancer therapy and could be of broad translational importance.
Long-term culture of hepatocytes: Effect of hormones on enzyme activities and metabolic capacity
Authors: John Dich, Constance Vind, Niels Grunnet
Journal: Hepatology (1988)

(i) Hepatocytes isolated from adult rats were cultured for 2 to 3 weeks on collagen in a modified, serum-free Waymouth medium containing fatty acids and varying concentrations of glucocorticoid, insulin and glucagon. (ii) In the presence of all three hormones, it was possible to maintain the content of DNA, the activity of glucokinase, pyruvate kinase, hexokinase and lactate dehydrogenase at initial levels for 2 to 3 weeks. The activity of glucokinase and pyruvate kinase was affected by the concentration of insulin. (iii) The activity of alcohol dehydrogenase was stable for 3 days and declined to about 25% of the initial level after 2 weeks of culture, irrespective of the presence of hormones. (iv) Maintenance of albumin secretion was dependent on the presence of glucocorticoid, and glucocorticoid and insulin showed an additive or, at some time points, a synergistic effect on its secretion. (v) The content of cytochrome P-450 could be kept at 65% of the initial level, provided that a relatively high concentration of dexamethasone was present (10(-6) M). (vi) In the absence of hormones, urea synthesis was 70% of initial levels throughout the experimental period. With insulin and glucocorticoid present, a high concentration of glucagon (10(-8) M) was required to maintain the synthesis of urea at this level. (vii) It is concluded that hepatocyte cultures as described in the present study may be a useful, well-defined system for long-term metabolic, pharmacologic and toxicologic studies.
The Effect of Clustering of Outcomes on the Association of Procedure Volume and Surgical Outcomes
Authors: Katherine S. Panageas, Deborah Schrag, Elyn Riedel, Peter B. Bach, Colin B. Begg
Journal: Annals of Internal Medicine (2003)

Background: A large body of literature documents associations between the volume of cases a hospital or surgeon treats and clinical outcomes. Most of these studies have used conventional statistical methods that do not recognize the fact that hospitals or surgeons with similar volumes may have very different outcomes because of systematic differences in processes of care, a phenomenon that exaggerates the true statistical significance of the effect of volume on outcome. Objective: To describe methods to assess the degree of this clustering of outcomes and to explore the impact of available statistical techniques that correct for clustering. Design: Reanalysis of 3 previously published volumeoutcome studies. Setting: Medicare beneficiaries 65 years of age or older undergoing surgery for colon, prostate, or rectal cancer in the population defined by the Surveillance, Epidemiology, and End Results cancer registries during 1992 to 1996. Patients: 3 data sets were analyzed to assess the impact of surgeon volume on outcomes: 1) 24166 colectomies performed by 2682 surgeons, 2) 10737 prostatectomies performed by 999 surgeons, and 3) 2603 rectal resections performed by 1141 surgeons. Measurements: Volumeoutcome trends were analyzed by a conventional method (logistic regression) and corrected for clustering. Two widely used statistical methods for analyzing clustered data, a random-effects model and generalized estimating equations, were used and compared, and the degree of clustering was presented graphically. Results: Substantial clustering was observed in the analyses involving morbidity end points. The 2 statistical techniques produced noticeably different results in some analyses. Conclusions: The presence of clustering represents variations in outcomes among providers with similar volumes. Thus, in volumeoutcome studies, the degree of clustering of outcomes should be characterized because it may provide insight into variations in quality of care.
Mechanism of action and rationale for cyclosporin A in psoriasis
Authors: JEAN F. BOREL
Journal: British Journal of Dermatology (1990)

Cyclosporin A (CyA) is the forerunner of a new generation of immunosuppressive drugs. It is highly effective in both antibody- and cell-mediated immunity and in inhibiting chronic inflammatory reactions. Cyclosporin A is, therefore, widely used to prevent rejection in clinical organ transplantation and appears to be very promising in the treatment of several autoimmune diseases, in particular psoriasis. Cyclosporin A is not only effective when given at the time of sensitization (prevention of rejection), but also when administered therapeutically during an immune response, such as during the active course of an autoimmune disease. The most important aspect of its immunosuppressive mechanism is the inhibition of lymphokine production secreted by activated T cells. The pharmacological effects of CyA are rapid in onset, dose-dependent and often quickly reversible when treatment is stopped.
Letter: Beta-blockers and fibrinous peritonitis.
Authors: R P Thompson, B T Jackson
Journal: BMJ (1975)

cadaver arm to be achieved.Separate measurements of trabecular bone mass, cortical bone mass, and bone mineral concentration have also been achieved in patients.The results of this study have been presented in March 1975 at the International Symposium on Computer Tomo- graphy in Bermuda and will be further ad- vanced at the European Society of Radiology in Edinburgh in June.It is important to stress that these results were obtained by modification of the E.M.I. brain scanner where the existence of a surrounding water reference makes accurate and absolute re- sults possible.-Weare, etc.,
Case-Control Studies
Authors: Hershel Jick
Journal: JAMA (1982)

<h3>To the Editor.—</h3> The article by Hayden et al (1982;247:326-331) on the methodology of the case-control study contains a factual error in describing articles published previously.<sup>1,2</sup>They report that in two studies of reserpine and breast cancer, "patients with thyrotoxicosis, renal disease, or cardiovascular disease were excluded from the control, non-breast-cancer groups..." This statement is incorrect. Such patients were excluded from the control group<i>only</i>if these diseases caused admission. All other control patients with such diseases were, of course, included. The same criteria were applied to the case group—namely, women were excluded if they came into the hospital because of thyroid or cardiovascularrenal disease. The principle involved in such studies is that the same criteria for exclusion must be applied to both cases and control subjects.<sup>3</sup>In the matter of reserpine and breast cancer, it should be obvious to even someone without formal epidemiologic training that if
715. Targeted Delivery of Antisense Oligonucleotide and siRNA into Lung Cancer Cells
Authors: Shyh-Dar Li, Leaf Huang
Journal: Molecular Therapy (2006)

Selective gene inhibition by antisense oligonucleotide (AS-ODN) or siRNA therapeutics promises the treatment of diseases that can not be cured by conventional drugs. However, antisense therapy is hindered due to poor stability in physiological fluids and limited intracellular uptake of AS-ODN and siRNA. To address these problems, a ligand targeted and sterically stabilized nanoparticle formulation is developed in our lab. Human lung cancer cells over-express the sigma receptor on their surface, thus can be targeted with a specific ligand such as anisamide. AS-ODN or siRNA against human survivin was mixed with a carrier DNA, calf thymus DNA, before complexed with protamine, a highly positively charged peptide. The resulting particles were coated with cationic liposomes consisting of DOTAP and cholesterol (1:1, molar ratio) to obtain stable LPD (liposome-protamine-DNA) nanoparticles. Ligand targeting and steric stabilization were then introduced by incubating preformed LPD nanoparticles with DSPE-PEG-anisamide, a PEGylated ligand lipid developed earlier in our lab, by the post insertion method. Non-targeted nanoparticles coated with DSPE-PEG were also prepared as a control. Antisense activities of nanoparticles were determined by survivin mRNA down-regulation, survivin protein down-regulation, ability to trigger apoptosis in tumor cells, tumor cell growth inhibition, and chemosensitization of the treated tumor cells to anticancer drugs. We found that tumor cell delivery and antisense activity of PEGylated nanoparticles were sequence dependent and rely on the presence of the anisamide ligand and could be competed by excess free ligand. Preliminary in vivo data showed that PEGylated LPD deliver siRNA predominantly into tumors after i.v. injection. Our encouraging results suggest that the ligand targeted and sterically stabilized nanoparticles can provide a selective delivery of AS-ODN and siRNA into lung cancer cells and perform antisense therapeutics. This research was supported by Industrial Technology Research Institute, Taiwan.