tbuckley/cabot-search huggingface dataset:
Abstract 3797: Regulation and function of the mucin-like glycoprotein podoplanin in glioma.
Authors: Heike Peterziel, Julia Müller, Danner Andreas, Sebastian Barbus, Haikun Liu, Philipp Pfenning, Patrick N. Harter, Michel Mittelbronn, Wolfgang Wick, Günther Schuetz, Bernhard Radlwimmer, Peter Lichter, Jochen Hess, Peter Angel
Journal: Cancer Research (2013)

Abstract Podoplanin (PDPN) is a mucin like type-1 transmembrane protein consisting of 162 amino acids, which comprises a highly glycosylated extracellular domain and a nine amino acid intracellular domain. The specific expression of PDPN on lymphatic but not on blood vascular endothelial cells has established application as a histological marker for lymphangiogenesis and lymphatic vessels in different species. PDPN is highly expressed in tumors of different origin, including squamous cell cancers, germinal neoplasia and tumors of the central nervous system. Recently, we found strong overexpression of PDPN in human astrocytic brain tumors, specifically in primary glioblastoma multiforme (GB). Regulation of PDPN expression involves increased PI3 kinase activation, subsequent activation of protein kinaseB/Akt and the downstream transcription factor AP-1. Activation of this pathway is mediated by loss of PTEN function, consistently, mice lacking Pten exhibit elevated Pdpn protein levels in the subventricular zone of the brain tissue. Additionally, PDPN expression is subject to negative transcriptional regulation by promoter methylation in human GB and in glioma cell lines. In patients high expression of PDPN is associated with poor prognosis. Silencing of PDPN results in a decrease in proliferation, migration and invasion of glioma cell lines in vitro and slows down the migration in orthotopic brain slices. Consistently, tumor formation after injection of PDPN knock-down cells into SCID mice is significantly reduced compared to tumors after injection of parental cells. These data highlight a functional role of PDPN in glioma progression and suggest targeting of PDPN expression as a promising strategy for the treatment of patients with primary GB. Citation Format: Heike Peterziel, Julia Müller, Danner Andreas, Sebastian Barbus, Haikun Liu, Philipp Pfenning, Patrick N. Harter, Michel Mittelbronn, Wolfgang Wick, Günther Schuetz, Bernhard Radlwimmer, Peter Lichter, Jochen Hess, Peter Angel. Regulation and function of the mucin-like glycoprotein podoplanin in glioma. [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 3797. doi:10.1158/1538-7445.AM2013-3797
Isoform-Selective Physical Coupling of TRPC3 Channels to IP <sub>3</sub> Receptors in Smooth Muscle Cells Regulates Arterial Contractility
Authors: Adebowale Adebiyi, Guiling Zhao, Damodaran Narayanan, Candice M. Thomas-Gatewood, John P. Bannister, Jonathan H. Jaggar
Journal: Circulation Research (2010)

Inositol 1,4,5-trisphosphate (IP(3))-induced vasoconstriction can occur independently of intracellular Ca(2+) release and via IP(3) receptor (IP(3)R) and canonical transient receptor potential (TRPC) channel activation, but functional signaling mechanisms mediating this effect are unclear.Study mechanisms by which IP(3)Rs stimulate TRPC channels in myocytes of resistance-size cerebral arteries.Immunofluorescence resonance energy transfer (immuno-FRET) microscopy using isoform-selective antibodies indicated that endogenous type 1 IP(3)Rs (IP(3)R1) are in close spatial proximity to TRPC3, but distant from TRPC6 or TRPM4 channels in arterial myocytes. Endothelin-1 (ET-1), a phospholipase C-coupled receptor agonist, elevated immuno-FRET between IP(3)R1 and TRPC3, but not between IP(3)R1 and TRPC6 or TRPM4. TRPC3, but not TRPC6, coimmunoprecipitated with IP(3)R1. TRPC3 and TRPC6 antibodies selectively inhibited recombinant channels, but only the TRPC3 antibody blocked IP(3)-induced nonselective cation current (I(Cat)) in myocytes. TRPC3 knockdown attenuated immuno-FRET between IP(3)R1 and TRPC3, IP(3)-induced I(Cat) activation, and ET-1 and IP(3)-induced vasoconstriction, whereas TRPC6 channel knockdown had no effect. ET-1 did not alter total or plasma membrane-localized TRPC3, as determined using surface biotinylation. RT-PCR demonstrated that C-terminal calmodulin and IP(3)R binding (CIRB) domains are present in myocyte TRPC3 and TRPC6 channels. A peptide corresponding to the IP(3)R N-terminal region that can interact with TRPC channels activated I(Cat). A TRPC3 CIRB domain peptide attenuated IP(3)- and ET-1-induced I(Cat) activation and vasoconstriction.IP(3) stimulates direct coupling between IP(3)R1 and membrane-resident TRPC3 channels in arterial myocytes, leading to I(Cat) activation and vasoconstriction. Close spatial proximity between IP(3)R1 and TRPC3 establishes this isoform-selective functional interaction.
The 28th Amendment
Authors: Thomas J. Romano
Journal: Annals of Internal Medicine (1999)

Letters5 October 1999The 28th AmendmentThomas J. Romano, MD, PhDThomas J. Romano, MD, PhDWheeling, WV 26003 (Romano)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-7-199910050-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I feel compelled to comment on the editorial on the 28th Amendment (1). I believe that a constitutional amendment guaranteeing health care is a bad idea. Bureaucrats and politicians will control health care even more than they do now, to the detriment of patient care and physicians' sanity. A 28th Amendment as described by the authors would burden individual practitioners with more and more intolerable demands and restrictions.I learned very early in life that for every right there is a responsibility. If the U.S. government truly wishes to have any say in how health care is ...Reference1. Davidoff F, Reinecke RD. The 28th Amendment [Editorial]. Ann Intern Med. 1999;130:692-4. LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Wheeling, WV 26003 (Romano) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe 28th Amendment Frank Davidoff and Robert D. Reinecke The 28th Amendment Ruric Anderson The 28th Amendment Frank Davidoff and Robert D. Reinecke The 28th Amendment Richard L. Neubauer The 28th Amendment Frederick Paola Metrics 5 October 1999Volume 131, Issue 7Page: 542-543KeywordsDisabilitiesHealth careImmunityMedical educationMedicarePatients Issue Published: 5 October 1999 CopyrightCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Twenty-eight-joint counts invalidate the DAS28 remission definition owing to the omission of the lower extremity joints: a comparison with the original DAS remission
Authors: R Landewe
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To compare 28 joint disease activity score (DAS28) remission with comprehensive joint count DAS remission in rheumatoid arthritis. <b>Methods:</b> 620 actually measured paired observations of DAS28 and DAS were analysed in 155 patients. Discordant observations (either DAS or DAS28 below remission cut off level: 1.6 for DAS and 2.6 for DAS28) and concordant observations (both DAS and DAS28 below their remission cut off level) were analysed separately. <b>Results:</b> 91 of 620 paired DAS observations (15%) were discordant; 87 (in 53 patients) comprised observations in which the DAS28 remission criterion, but not the DAS remission criterion, was met. The reverse was found in only four observations, which were therefore omitted. With the original DAS as standard, DAS28 sensitivity was 95% and specificity 84%. Probability plots showed a swollen joint count &gt;0 in 75% of discordant pairs <i>v</i> 48% of concordant pairs. The same was found for total joint count (TJC &gt;0 in 90% <i>v</i> 40%; median TJC, 0 <i>v</i> 6) and patient global assessment, but not for ESR. Individual joint analysis showed that 51% of discordant <i>v</i> 18% of concordant observations (p&lt;0.0005) had involvement of lower extremity joints that are not included in the DAS28. <b>Conclusions:</b> DAS remission is more conservative than DAS28 remission. Activity (tenderness and swelling) in joints not included in the reduced joint counts (ankles, feet) mainly account for the discrepancy between the two assessments. DAS28 remission at a cut off level of 2.6 has insufficient construct validity and should be used with caution in clinical practice and clinical trials.
A VARIATION IN THE OPERATIVE TREATMENT OF STRUCTURAL SCOLIOSIS
Authors: ARMITAGE WHITMAN
Journal: JAMA (1927)

The development of the operation which I shall describe may perhaps be made clearer if I outline the steps of its gradual evolution.  On my return from the war in 1919, I undertook the treatment of a number of patients with scoliosis, among whom was J. M., a boy who had already been under treatment for a number of years. This treatment had consisted of jackets of various types, none of which had succeeded in checking the progress of his deformity, which went on, as may be seen in the accompanying illustrations, to the most distressing extreme. The rotation of the vertebrae and the consequent distortion of the ribs made so sharp a convexity posteriorly that in spite of the most careful padding and personal application of the jacket, the patient would from time to time develop a pressure sore. He would then enter the hospital, have his jacket removed
Oncostatin M is a proinflammatory mediator. In vivo effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules.
Authors: V Modur, M J Feldhaus, A S Weyrich, D L Jicha, S M Prescott, G A Zimmerman, T M McIntyre
Journal: Journal of Clinical Investigation (1997)

Oncostatin M is a member of the IL-6 family of cytokines that is primarily known for its effects on cell growth. Endothelial cells have an abundance of receptors for oncostatin M, and may be its primary target. We determined if oncostatin M induces a key endothelial cell function, initiation of the inflammatory response. We found that subcutaneous injection of oncostatin M in mice caused an acute inflammatory reaction. Oncostatin M in vitro stimulated: (a) polymorphonuclear leukocyte (PMN) transmigration through confluent monolayers of primary human endothelial cells; (b) biphasic PMN adhesion through rapid P-selectin expression, and delayed adhesion mediated by E-selectin synthesis; (c) intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 accumulation; and (d) the expression of PMN activators IL-6, epithelial neutrophil activating peptide-78, growth-related cytokine alpha and growth-related cytokine beta without concomitant IL-8 synthesis. The nature of the response to oncostatin M varied with concentration, suggesting high and low affinity oncostatin M receptors independently stimulated specific responses. Immunohistochemistry showed that macrophage-like cells infiltrating human aortic aneurysms expressed oncostatin M, so it is present during a chronic inflammatory reaction. Therefore, oncostatin M, but not other IL-6 family members, fulfills Koch's postulates as an inflammatory mediator. Since its effects on endothelial cells differ significantly from established mediators like TNFalpha, it may uniquely contribute to the inflammatory cycle.
The Patient's Bill of Rights Becomes Law
Authors: William J. Curran
Journal: New England Journal of Medicine (1974)

It is declared to be the public policy of this state that the interests of patients be protected by a patient's bill of rights.... [Minnesota Laws of 1973, Chapter 688.]DURING the past few years, hospitals and neighborhood health centers in the United States have been adopting documents called a "patient's bill of rights." Among the best known are the statements or booklets published by the Beth Israel Hospital in Boston and the Martin Luther King Health Center in New York City. In November, 1972, the Board of Trustees of the American Hospital Association (AHA) adopted such a statement containing . . .
An NF-κB pathway–mediated positive feedback loop amplifies Ras activity to pathological levels in mice
Authors: Jaroslaw Daniluk, Yan Liu, Defeng Deng, Jun Chu, Haojie Huang, Sebastian Gaiser, Zobeida Cruz-Monserrate, Huamin Wang, Baoan Ji, Craig D. Logsdon
Journal: Journal of Clinical Investigation (2012)

Genetic mutations that give rise to active mutant forms of Ras are oncogenic and found in several types of tumor. However, such mutations are not clear biomarkers for disease, since they are frequently detected in healthy individuals. Instead, it has become clear that elevated levels of Ras activity are critical for Ras-induced tumorigenesis. However, the mechanisms underlying the production of pathological levels of Ras activity are unclear. Here, we show that in the presence of oncogenic Ras, inflammatory stimuli initiate a positive feedback loop involving NF-κB that further amplifies Ras activity to pathological levels. Stimulation of Ras signaling by typical inflammatory stimuli was transient and had no long-term sequelae in wild-type mice. In contrast, these stimuli generated prolonged Ras signaling and led to chronic inflammation and precancerous pancreatic lesions (PanINs) in mice expressing physiological levels of oncogenic K-Ras. These effects of inflammatory stimuli were disrupted by deletion of inhibitor of NF-κB kinase 2 (IKK2) or inhibition of Cox-2. Likewise, expression of active IKK2 or Cox-2 or treatment with LPS generated chronic inflammation and PanINs only in mice expressing oncogenic K-Ras. The data support the hypothesis that in the presence of oncogenic Ras, inflammatory stimuli trigger an NF-κB–mediated positive feedback mechanism involving Cox-2 that amplifies Ras activity to pathological levels. Because a large proportion of the adult human population possesses Ras mutations in tissues including colon, pancreas, and lung, disruption of this positive feedback loop may be an important strategy for cancer prevention.
Changes in Urinary Arsenic Methylation Profiles in a 15-Year Interval after Cessation of Arsenic Ingestion in Southwest Taiwan
Authors: Yung-Kai Huang, Ya-Li Huang, Yu-Mei Hsueh, Jimmy Tse-Jen Wang, Mo-Hsiung Yang, Chien-Jen Chen
Journal: Environmental Health Perspectives (2009)

Inorganic arsenic (iAs) is carcinogenic to humans. Methylated metabolites of arsenic (As) found in the urine could serve as potential tools for screening and early detection of cancer in populations exposed to As. Relatively little information is available regarding changes in As methylation profiles after cessation of As exposure.We examined the changes in urinary arsenic (uAs) species profiles over 15 years in a cancer-free population that has ceased heavy and prolonged ingestion of As.In 1989, a cohort study was carried out with 1,081 adults who resided in three villages in southwestern Taiwan where arseniasis was hyperendemic. After 15 years of follow-up, a subgroup of 205 cancer-free participants had completed all interviews and had uAs methylation data available. We used this group in our statistical analysis. Arsenic species were measured by high-performance liquid chromatography-hydride generation-atomic absorption spectrometry.We compared the initial analyses from 1989 with those performed 15 years later and found that the average differences for the proportion of urinary iAs, monomethylarsonic acid (MMA(V)), and dimethylarsinic acid (DMA(V)) were -4.90%, -6.80%, and 11.69%, respectively. The elderly and those residents with longer periods of consuming high-As artesian well water exhibited greater changes (decreases) in %MMA(V).The As methylation profiles indicate increased efficiency in As metabolism in residents after cessation of long-term exposure to high-level As. Moreover, the decreased %MMA(V) was more pronounced in the elderly cancer-free subcohort subjects.
The Great Pox: The French Disease in Renaissance Europe
Authors: Ruben D. Rumbaut
Journal: JAMA (1997)

In 1495 syphilis hit Renaissance Europe like a meteorite. It began in a besieged Naples amidst invading  troops under Charles VIII, which included soldiers of fortune from many European countries, mostly Spaniards. The blaming game started immediately. The Italians acted first, and called it morbus gallicus , the French Disease. The  retaliated with Neapolitan Disease. Then accusatory eyes turned to the Iberian Peninsula, not only because the Jews (as well as the Moors) had been expelled from Spain in 1492 and became handy scapegoats, but especially because of the Columbus crew. The crew left Palos Bay in August 1492, eventually landed in some Caribbean islands (mainly Hispaniola and Cuba), and returned to Palos in March 1493. That group of travelers are considered, by those who believe in the Columbian theory, responsible for the syphilization of Europe.  So syphilis (which still had no name but the vernacular Great Pox) probably
Abstract 1678: Metastatic breast cancer cell phenotype is regulated by autophagy.
Authors: Yi Li, Monica J. Lewis, Jianzhong Liu, James J. Cody, Douglas R. Hurst
Journal: Cancer Research (2013)

Abstract Autophagy is a catabolic process that is tightly regulated during normal cell growth, development, and homeostasis. Although it may be death inducing, it is also an important survival mechanism for cells in stressful environments, including hypoxia, nutrient deprivation, chemical or physical pressure, or detachment from colonies. Considering the stress associated with the process of metastasis, we hypothesized that autophagy may play a role in the ability of breast cancer cells to survive and metastasize. To test this, we first compared cell proliferation after autophagic induction between metastatic breast cancer cell lines (MDA-MB-231 and -435), a non-metastatic breast cancer cell line (MDA-MB-436), and a ‘normal’ breast epithelial cell line (MCF10A). Both metastatic cell lines continued to proliferate following induction of autophagy; however, the non-metastatic and normal cell lines were growth-inhibited. Autophagy was also more rapidly induced by rapamycin in the metastatic cell lines as demonstrated by an increase in LC3II expression. To test the different survival capabilities between metastatic and normal cells, we selected cells through five rounds of starvation with Earle's balanced salt solution (EBSS) and compared their ability to induce autophagy. Although both the normal and metastatic cells maintained their ability to proliferate under normal conditions, the MDA-MB-231 cells that survived starvation (231-EB5) proliferated more rapidly than the parental population following induction of autophagy. In contrast, both MCF10A and MCF10A-EB5 cells were growth-inhibited. The 231-EB5 cells induced autophagy more rapidly than the parental population as demonstrated by increased expression of LC3II (analyzed by immunoblot) and increased LC3 puncta (analyzed by immunofluorescence). Migration of parental 231 cells was inhibited by rapamycin; however, there was no change in the ability of 231-EB5 cells to migrate after treatment with rapamycin. Growth in three dimensions also was significantly altered. MCF10A-EB5 cells were more extended compared to the spherical growth of the parental MCF10A cells. Protrusions emitted from the 231-EB5 cells were more rounded compared to the extended spikes of the parental 231 cells. Altogether, these results demonstrate that select populations derived from metastatic breast cancer cells have different abilities to survive, proliferate, and migrate following induction of autophagy, suggesting that autophagy may be a key mechanism for tumor progression and metastasis. Citation Format: Yi Li, Monica J. Lewis, Jianzhong Liu, James J. Cody, Douglas R. Hurst. Metastatic breast cancer cell phenotype is regulated by autophagy. [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 1678. doi:10.1158/1538-7445.AM2013-1678
Safety of Lumbar Puncture for Children With Acute Lymphoblastic Leukemia and Thrombocytopenia
Authors: Scott C. Howard
Journal: JAMA (2000)

Patients with thrombocytopenia are at risk for spontaneous or procedure-related hemorrhage. Whether such patients can safely undergo lumbar puncture (LP) without prophylactic platelet transfusion is unknown.To determine whether an association exists between thrombocytopenia and LP complications among children with acute lymphoblastic leukemia.Retrospective review of the records of 958 consecutive children (median age, 5.5 years) with newly diagnosed acute lymphoblastic leukemia who were treated at a pediatric cancer center between February 1984 and July 1998.All patients underwent a diagnostic LP followed by a median of 4 LPs to instill intrathecal chemotherapy.Serious complications of LP occurring during the remission induction and consolidation treatment periods (when thrombocytopenia is likely to occur), defined as any neurologic, infectious, or hemorrhagic problems related to the procedure, reported by platelet count at the time of the procedure.Of the 5223 LPs evaluated, 29 were performed at platelet counts of 10 x 10(9)/L or less, 170 at platelet counts of 11 to 20 x 10(9)/L, and 742 at platelet counts of 21 to 50 x 10(9)/L. No serious complications were encountered, regardless of the platelet count. The 95% confidence interval for the proportion of serious complications in the 199 patients with platelet counts of 20 x 10(9)/L or less was 0% to 1.75% and that for the 941 patients with platelet counts of 50 x 10(9)/L or less was 0% to 0.37%.In our study of children undergoing remission induction or consolidation therapy for acute lymphoblastic leukemia, serious complications of LP were not observed, regardless of platelet count. Prophylactic platelet transfusion is not necessary in children with platelet counts higher than 10 x 10(9)/L. Due to the small number of patients in our study with platelet counts of 10 x 10(9)/L or less, conclusions cannot yet be drawn for such patients. JAMA. 2000;284:2222-2224.