tbuckley/cabot-search huggingface dataset:
Methylation of Tumor-Related Genes in Neoadjuvant-Treated Gastric Cancer: Relation to Therapy Response and Clinicopathologic and Molecular Features
Authors: Rudolf Napieralski, Katja Ott, Markus Kremer, Karen Becker, Anne-Laure Boulesteix, Florian Lordick, Jörg Rüdiger Siewert, Heinz Höfler, Gisela Keller
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The objective of this study was to analyze the hypermethylation of tumor-related gene promoters for an association with therapy response and clinicopathologic features of neoadjuvant-treated gastric cancer patients. Furthermore, we analyzed the relationship of promoter hypermethylation with microsatellite instability and loss of heterozygosity (LOH) of the tumors. Experimental Design: Pretherapeutic biopsies of 61 patients, subsequently treated with cisplatin and 5-fluorouracil, were studied. Methylation analysis of six gene promoters was done using MethyLight technology. Microsatellite analysis was mainly done in previous studies. Results: The methylation frequencies for the analyzed genes were MGMT, 44%; LOX, 53%; p16, 46%, E-cadherin, 30%; 14-3-3σ, 69%; and HPP1, 82%. Concordant methylation of more than three genes was found in 46% of the tumors and was inversely correlated with the LOH rate (P = 9 × 10−5) and associated with female gender (P = 0.049), nonintestinal type tumors (P = 0.04), and a nonproximal tumor location (P = 0.003). No statistically significant association between the methylation of a single gene or the concordant methylation of multiple genes was found with response or survival. However, patients with none or only one methylated gene showed a trend for an increase in survival (5-year survival rate, 83% versus 35%; P = 0.067). Conclusion: The highly significant inverse correlation of promoter methylation and LOH rate reflects major alternative molecular pathways in gastric carcinogenesis. Methylation was not statistically significantly associated with the response to cisplatin/5-fluorouracil–based therapy. However, a concordant methylation of more than three genes defines subgroups of gastric cancer with distinct biological and genetic characteristics.
Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma
Authors: Güllü Görgün, Elisabetta Calabrese, Ender Soydan, Teru Hideshima, Giulia Perrone, Madhavi Bandi, Diana Cirstea, Loredana Santo, Yiguo Hu, Yu-Tzu Tai, Sabikun Nahar, Naoya Mimura, Claire Fabre, Noopur Raje, Nikhil Munshi, Paul Richardson, Kenneth C. Anderson
Journal: Blood (2010)
Experimental inhalation of fragrance allergens in predisposed subjects: effects on skin and airways
Authors: A. Schnuch, E. Oppel, T. Oppel, H. Römmelt, M. Kramer, E. Riu, U. Darsow, B. Przybilla, D. Nowak, R.A. Jörres
Journal: British Journal of Dermatology (2009)

Journal Article Experimental inhalation of fragrance allergens in predisposed subjects: effects on skin and airways Get access A. Schnuch, A. Schnuch Information Network of Departments of Dermatology, IVDK–Zentrale, Institut an der Universität Göttingen, Von‐Sieboldstr. 3, D‐37075 Göttingen, Germany Axel Schnuch. E‐mail: aschnuch@med.uni‐goettingen.de Search for other works by this author on: Oxford Academic Google Scholar E. Oppel, E. Oppel Department of Dermatology, Ludwig‐Maximilians‐University, Munich, GermanyInstitute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Campus Inner City, Ludwig‐Maximilians‐University, Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar T. Oppel, T. Oppel Department of Dermatology, Ludwig‐Maximilians‐University, Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar H. Römmelt, H. Römmelt Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Campus Inner City, Ludwig‐Maximilians‐University, Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Kramer, M. Kramer Department of Oto‐Rhino‐Laryngology, Head and Neck Surgery, Campus Großhadern, Ludwig‐Maximilians‐University, Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar E. Riu, E. Riu Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Campus Inner City, Ludwig‐Maximilians‐University, Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar U. Darsow, U. Darsow Department of Dermatology and Allergy, Biederstein, and Technical University, Division of Environmental Dermatology and Allergy Helmholtz Center, Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar B. Przybilla, B. Przybilla Department of Dermatology, Ludwig‐Maximilians‐University, Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar D. Nowak, D. Nowak Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Campus Inner City, Ludwig‐Maximilians‐University, Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar R.A. Jörres R.A. Jörres Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Campus Inner City, Ludwig‐Maximilians‐University, Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 3, 1 March 2010, Pages 598–606, https://doi.org/10.1111/j.1365-2133.2009.09510.x Published: 01 March 2010
Thyroid Suppressibility: Follow-up for Two Years after Antithyroid Treatment
Authors: R. C. Lowry, D. Lowe, D. R. Hadden, D. A. D. Montgomery, J. A. Weaver
Journal: BMJ (1971)

In hyperthyroidism suppression and non-suppression of early radioiodine neck uptake by exogenous thyroid hormone after a course of antithyroid drugs does not indicate clearly those patients who will eventually relapse or have a remission. Sixty-four hyperthyroid patients have been followed up for two years after an 18 to 24 months9 course of carbimazole. Twenty-eight patients had suppressed at the end of the carbimazole course and 20 of these remained in remission for two years, and 36 were non-suppressed and 21 of these relapsed. Patients with the highest neck uptakes relapsed soonest after stopping treatment. Pronounced rebound occurred in neck uptakes at one month after stopping treatment, both in patients who relapsed and in those who remained in remission. By one year after stopping treatment those who remained in remission had shown a further fall in early neck uptake. In two patients who relapsed after exposure to stressful events no change in 20-minute radioiodine neck uptakes was found in relation to the supposed stress.
Argonaute2 promotes tumor metastasis by way of up-regulating focal adhesion kinase expression in hepatocellular carcinoma
Authors: Na Cheng, Yandong Li, Ze-Guang Han
Journal: Hepatology (2012)

Hepatocellular carcinoma (HCC) is one of the most common cancers and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. However, the mechanisms that contribute to tumor metastasis remain unclear. Here we evaluate the effect of Argonaute2 (Ago2), a member of the Ago gene family that plays a role in short interfering RNA-mediated gene silencing, on HCC tumorigenesis, and metastasis. We found that Ago2 was frequently up-regulated in HCC specimens compared to that in corresponding adjacent nontumor liver. Interestingly, Ago2 overexpression can promote proliferation, colony formation in an anchor-independent manner, migration, tumorigenicity, and metastasis of HCC cells in vivo; in contrast, Ago2 knockdown can restrict anchor-independent colony formation, migration, and tumor metastasis of HCC cells in vivo. However, known microRNAs related to tumor metastasis appeared not be deregulated with Ago2 overexpression in HCC cells; even the knockdown of Dicer, which is responsible for microRNA biosynthesis, did not abolish the actions of Ago2 in HCC cells. Significantly, focal adhesion kinase (FAK), a well-known molecule associated with tumor metastasis, was up-regulated as a result of Ago2 overexpression. Chromatin immunoprecipitation assay showed that Ago2 can bind to the FAK promoter and then trigger its transcription. Moreover, an increased DNA copy number of Ago2 on chromosome 8q24, one of the most frequent DNA amplified regions, was validated and shown by way of fluorescence in situ hybridization.Our data demonstrate that Ago2 overexpression, as a result of genomic DNA amplification, promotes HCC tumorigenesis and metastasis by way of up-regulation of FAK transcription, thereby providing new insight into HCC progression and Ago2 function.
Abstract 5408: Enhancement of the anti-tumor activity of afatinib by inhibition of glycolysis in non-small cell lung cancer harboring the EGFR T790M mutation .
Authors: Byoung Chul Cho, Hyun-Jung Kim, Sun Min Lim
Journal: Cancer Research (2013)

Abstract The secondary epidermal growth factor receptor (EGFR) T790M is the most common mechanism of resistance to reversible EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. Although afatinib (BIBW2992), a second-generation irreversible EGFR TKI, was expected to overcome the acquired resistance, it showed limited efficacy in a recent phase III clinical study. In this study, we found that the inhibition of glycolysis using 2-deoxy-D-glucose (2DG) improves the efficacy of afatinib in H1975 and PC9-GR, which are NSCLC cells with EGFR T790M. Treatment with a combination of 2DG and afatinib induced intracellular ATP depletion in both H1975 and PC9-GR cells, resulting in activation of AMP-activated protein kinase (AMPK). AMPK activation played a central role in the cytotoxicity of the combined treatment with 2DG and afatinib through inhibition of mammalian target of rapamycin (mTOR). The alteration of the AMPK/mTOR signaling pathway by inhibition of glucose metabolism induced specific downregulation of Mcl-1, a member of anti-apoptotic Bcl-2 family, through translational control. The enhancement of afatinib sensitivity by treatment of 2DG was confirmed in in vivo PC9-GR xenograft model. In conclusion, this study examined whether inhibition of glucose metabolism using 2DG enhances the sensitivity to afatinib in NSCLC cells with EGFR T790M through regulation of AMPK/mTOR/Mcl-1 signaling pathway. These data suggest that the combined use of an inhibitor of glucose metabolism and afatinib is a potential therapeutic strategy for treatment of patients with acquired resistance to reversible EGFR TKIs due to secondary EGFR T790M. Citation Format: Byoung Chul Cho, Hyun-Jung Kim, Sun Min Lim. Enhancement of the anti-tumor activity of afatinib by inhibition of glycolysis in non-small cell lung cancer harboring the EGFR T790M mutation . [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 5408. doi:10.1158/1538-7445.AM2013-5408 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
"CONTROLLING THE ODOR AND TASTE OF ARSPHENAMINE"
Authors: C. J. Broeman
Journal: JAMA (1926)

To the Editor:  —InThe Journal, March 20, page 840, I read with much interest Dr. J. H. Stokes' short article on Controlling the Odor and Taste of Arsphenamine, in which he states that he allows a strong wintergreen or clove wafer to dissolve on the patient's tongue during the injection.  I frequently have patients complain of the same peculiar odor and taste while receiving an intravenous injection of arsphenamine, particularly neo-arsphenamine, and I have always found that this could be almost entirely relieved by smelling a little cotton well moistened with bay-rum. The reason why I used bay-rum is that when looking about for something with a decided odor I happened to have some handy in my office, and it has a peculiar penetrating odor. I have been using bay-rum for this purpose for the last ten years and have been well satisfied with the results, although I have
Synthesis and Secretion of Corticosteroid-Binding Globulin by Rat Liver
Authors: Jeffrey N. Weiser, Yung-Shun Do, David Feldman
Journal: Journal of Clinical Investigation (1979)

Classical glucocorticoid receptors (type II) have a high affinity for synthetic and natural glucocorticoids. We have previously demonstrated an additional binding site in kidney cytosol (type III) which has a high affinity for corticosterone but a low affinity for dexamethasone. In many ways, this binder resembles plasma corticosteroid-binding globulin (CBG). The first goal of this study was to determine the organ distribution of the type III binding sites. Cytosol was prepared from isolated cells to avoid plasma contamination. Of the tissues examined, type III sites were found only in liver and kidney; sites were absent from thymocytes, IM-9 lymphocytes, adipocytes, and bone cells. The second goal of this study was to ascertain whether CBG is synthesized in liver and kidney. Liver and kidney slices were incubated in vitro and the concentration of type III sites was seen to rise in hepatic cytosol and incubating medium but not kidney. To verify the impression that liver was synthesizing and secreting CBG, the following experiments were performed: (a) To demonstrate that type III sites were CBG, steroid-binding profiles and migration on polyacrylamide gel electrophoresis were shown to be identical for hepatic type III sites and serum. (b) To indicate that the rise in type III sites was dependent on protein synthesis, it was shown that cycloheximide blocked the appearance of new type III sites. (c) To establish that the type III sites were being secreted, in situ liver perfusion experiments showed time-dependent release of new sites into the perfusate. In conclusion, liver synthesizes and secretes type III sites, a finding previously suspected but never proved. The presence of type III sites in kidney remains to be explained.
The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells
Authors: Aurelie T Bauquet, Hulin Jin, Alison M Paterson, Meike Mitsdoerffer, I-Cheng Ho, Arlene H Sharpe, Vijay K Kuchroo
Journal: Nature Immunology (2008)
A case of partial dedicator of cytokinesis 8 deficiency with altered effector phenotype and impaired CD8+ and natural killer cell cytotoxicity
Authors: Raquel Ruiz-García, Sara Lermo-Rojo, Luis Martínez-Lostao, Esther Mancebo, Sergio Mora-Díaz, Estela Paz-Artal, Jesús Ruiz-Contreras, Alberto Anel, Luis I González-Granado, Luis M Allende
Journal: Journal of Allergy and Clinical Immunology (2014)
THE ETIOLOGY AND PATHOLOGY OF CYSTOCELE AND A NEW OPERATION FOR ITS RELIEF.
Authors: J. RIDDLE GOFFE
Journal: JAMA (1904)

The early procedures for the relief of cystocele consisted simply in building up a strong perineal body that should retain the prolapsed tissue within the vulva. Simon practiced this for many years, but his experience developed the fact that this method was only a temporary expedient; the weight of the sustained mass and intra-abdominal pressure gradually absorbed the artificially constructed dam and allowed the former condition to be reproduced. Marion Sims brought his batteries to bear directly on the offending tissues, and devised the procedure known as anterior colporrhaphy. Emmet followed the suggestion of Sims, and improved on it, modifying in various ways the denuded surfaces, with the idea of building up a resisting line of tissue that should act as a lever in holding the cervix high in the hollow of the sacrum. E. C. Dudley shifted the seat of operation to the lateral sulci of the vagina in
Beneficial Effects of a Dietary Approaches to Stop Hypertension Eating Plan on Features of the Metabolic Syndrome
Authors: Leila Azadbakht, Ahmad Esmaillzadeh
Journal: Diabetes Care (2006)

We thank Esposito and Giugliano (1) for their attention to our study, in which we showed the beneficial effects of a Dietary Approaches to Stop Hypertension (DASH) eating pattern on components of the metabolic syndrome (2). DASH diet is similar to the Mediterranean diet; both have high levels of fiber and isoflavones and a large number of low–glycemic index foods such as vegetables and whole grains (3,4). We agree with Esposito and Giugliano that in the short term, our study (2) confirms the results reported by them previously (3). However, we discussed differences between DASH and Mediterranean diet in the conclusions section of our study (2).

We reported a 13-kg weight reduction in the weight-reducing diet and a 15- kg reduction in the DASH diet …
Statins and primary prevention of cardiovascular events
Authors: N. Donner-Banzhoff, A. Sonnichsen
Journal: BMJ (2008)

No change in strategy is needed despite the hype surrounding the recent JUPITER study

This week, the New England Journal of Medicine published the randomised controlled trial JUPITER,1 which compared rosuvastatin (20 mg daily) with placebo in 18 000 patients with no apparent vascular disease, low density lipoprotein cholesterol (LDL-C) of less than 3.4 mmol/l (130 mg/dl), and high sensitivity C reactive protein concentrations of 2.0 mg/l or higher. The combined primary end point was myocardial infarction, stroke, arterial revascularisation, hospital admission for unstable angina, or death from cardiovascular causes. The trial was stopped after a median of two years after a highly significant improvement in the primary end point with rosuvastatin (hazard ratio 0.56; 95% confidence interval 0.46 to 0.69; P<0.00001). It is hardly surprising that the JUPITER study is seen by many as opening the door to new avenues to prevention.

What do the results mean? Do we really have to change our ways of targeting our preventive efforts—for example, measure high sensitivity C reactive protein on a regular basis? …
Are Estrogens of Import to Primate/Human Ovarian Folliculogenesis?*
Authors: Steven F. Palter, Adriano B. Tavares, Ariel Hourvitz, Johannes D. Veldhuis, Eli Y. Adashi
Journal: Endocrine Reviews (2001)

The notion that estrogens play a meaningful role in ovarian folliculogenesis stems from a large body of in vitro and in vivo experiments carried out in certain rodent models, (e.g., rats) wherein the stimulatory role of estrogen on granulosa cell growth and differentiation is undisputed. However, evidence derived from these polyovulatory species may not be readily generalizable to the monoovulatory subhuman primates, let alone the human. Only recently, significant observations on the ovarian role(s) of estrogen have been reported for the primate/human. It is thus the objective of this communication to review the evidence for and against a role for estrogens in primate/human ovarian follicular development with an emphasis toward the application of the concepts so developed to contemporary reproductive physiology and to the practice of reproductive medicine. The role(s) of estrogens will be examined not only by analyzing the physiological evidence to the effect that these hormones control ovarian function and follicular growth, but also by summarizing the molecular evidence for the existence and distribution of the cognate receptors.
The Output of Pancreatic Protein after Pancreozymin: A Test of Pancreatic Exocrine Function.
Authors: Donald H. Hanscom
Journal: Annals of Internal Medicine (1964)

s1 October 1964The Output of Pancreatic Protein after Pancreozymin: A Test of Pancreatic Exocrine Function.Donald H. Hanscom, M.D., James V. Dunphy, M.D., Armand Littman, M.D., Ph.D., F.A.C.P.Donald H. Hanscom, M.D.Search for more papers by this author, James V. Dunphy, M.D.Search for more papers by this author, Armand Littman, M.D., Ph.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-4-804_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOur previous dose-response data on pancreozymin (PZ) in humans indicated progressively better discrimination between normal and pancreatic patients with increasing doses of PZ. With the new Jorpes-Mutt preparation of PZ it is possible to give still larger doses. A clinical test was developed measuring the protein (enzyme) output from the pancreas in response to intravenously injected PZ (Cecekin, Vitrum, Stockholm). A double lumen Dreiling tube collected gastric and duodenal contents separately. A secretin test was done by inecting 1.5 µ/kg of secretin and collecting six 10-min samples. Then secretin was given by continuous intravenous infusion at a rate of 1.5... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hines, Ill. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1964Volume 61, Issue 4Page: 804-805KeywordsEnzymesPancreasProteinsSecretin Issue Published: 1 October 1964 PDF DownloadLoading ...
Ethical Psychiatry and Biosocial Humanism
Authors: LOUIS JOLYON WEST
Journal: American Journal of Psychiatry (1969)

In discussing the ethical issues of special relevance to contemporary psychiatry, the author raises some provocative questions, ranging in subject from the practitioner's responsibility for the maintenance of professional competence to the ethical ramifications of some current treatment concepts. He concludes that psychiatry's task includes the development of a more satisfactory statement of human nature, from which a new and comprehensive ethical system can be derived.
Streptococcal-induced cell-mediated-immune destruction of cardiac myofibers in vitro.
Authors: L C Yang, P R Soprey, M K Wittner, E N Fox
Journal: The Journal of Experimental Medicine (1977)

We have demonstrated that T lymphocytes from the spleens of adult guinea pigs sensitized to group A streptococcal antigens are cytotoxic for cultured fetal guinea pig heart cells. Lymphocyte cytotoxicity, measured by 51Cr release from target cells, was stimulated by sensitization in vivo with group A whole cells, cell walls, and purified protoplast membranes emulsified with complete Freund's adjuvant (CFA). Sensitization with group C streptococcal antigens in CFA or CFA alone produced lymphocytes with little or no specific cytotoxic activity. Target cells of cultured fetal skeletal muscle, liver, or skin were relatively refractory to effector cell cytotoxicity. The presence of antigenic determinants on the membranes of cultured myofibers, cross-reacting with group A streptococcal cellular antigens, was confirmed by immunofluorescence. These data are discussed in terms of a model for poststreptococcal rheumatic myocarditis in which cell-mediated autoimmune mechanisms may participate.
Recent Advances in Hemophilia Care
Authors: Ruth Andrea Seeler
Journal: JAMA (1991)

This compact monograph reflects the current art and knowledge of hemophilia from a symposium in April 1989. By using a typed manuscript format, rapid publication was possible.  Problems are organized in six major groups: genetics, inhibitor management, complications of hemophilia treatment, clotting factor concentrates, orthopedic care, and von Willebrand's disease. Each of the major sections includes contributions from leaders in their respective fields. Bibliographies contain both the classic studies and the most recent contributions.  In the section on the management of inhibitors, all of the various strategies are nicely reviewed. Treatment had been frustrating to physicians and not very satisfactory for patients until the recent advent of porcine concentrates and immune tolerance induction regimens.  The tragedy of human immunodeficiency virus and hepatitis is all too clear. Prior to the disaster of the acquired immunodeficiency syndrome, chronic end-stage liver disease was the number two cause of death (after hemorrhage) in patients