tbuckley/cabot-search huggingface dataset:
Abstract 2136: Nuclear trafficking of Tie2 is associated with radioresistance of gliomas
Authors: Mohammad B. Hossain, Anupama Gururaj, Nahir Cortes-Santiago, Konrad Gabrusiewicz, Juan Fueyo, Candelaria Gomez-Manzano
Journal: Cancer Research (2012)

Abstract Resistance and relapse are still primary causes that result in poor effectiveness of chemo- and radiotherapy in glioblastoma multiforme (GBMs), the most frequent subtype of primary brain tumors in adults. Patients suffering from this disease exhibit a median survival that ranges from 9 to 15 month, and the disease invariably recur after therapy due to the presence of cells exhibiting a multidrug-resistance phenotype. Aberrant DNA repair pathways can enable tumor cells to survive DNA damage that is induced after chemotherapy and radiotherapy. Therefore, development of new therapeutic strategies requires the identification of key molecular pathways regulating the resistant phenotype of these tumors. Previous work from our laboratory showed that Tie2, a previously considered specific vascular tyrosine kinase receptor, was expressed in glioma tumors and in brain tumor stem cells. The degree of expression of Tie2 was related to the malignancy of these tumors, and played an essential role in the multidrug resistance phenotype of gliomas. Our current research is focused on deciphering the mechanisms underlying this critical function. We found that density of Tie2 receptors in the membrane decreased upon exposure to both ligand (angiopoietin 1, Ang1) and ionizing irradiation (IR). Immunoflurorescence studies using confocal microscope and subcellular fractionation followed by Western blot showed that Tie2 traffics from the cellular membrane to the nucleus upon both stimuli. Western blot analysis using antibodies against N- and C-terminus, and against phosphorylated-Tie2, indicated that the nuclear Tie2 is a full-length protein, and importantly that is phosphorylated at Tyr992. Of biological importance, to find the role of Tie2 in the nucleus, we irradiated the glioma cells, U251.Tie2, and found that ionizing radiation also helps Tie2 to move to the nucleus and importantly it binds with γH2AX one of the key DNA repair protein complex. By using confocal microscopy we found that Tie2 makes foci with γH2AX after DNA damage. We also found that after genotoxic stress like ionizing radiation or DNA-damaging drugs, Tie2-expressing cells were more resistant to DNA damaging effect, as assessed by cell viability assay and comet assay. Collectively, the nuclear Tie2 plays important role in the DNA repair which will result in the design of Tie2-targeting combinational therapies for patients with glioblastomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2136. doi:1538-7445.AM2012-2136
Differential distribution of annexins-I, -II, -IV, and -VI in synovium.
Authors: N J Goulding, J Dixey, E F Morand, R A Dodds, L S Wilkinson, A A Pitsillides, J C Edwards
Journal: Annals of the Rheumatic Diseases (1995)

To examine the distribution of four annexins in non-inflamed rheumatoid arthritic and osteoarthritic synovial tissue.Frozen sections were stained with monoclonal antibodies (MAb) specific for annexins-I, -II, -IV, and -VI, and for cell lineage related markers including CD68 and CD14 (macrophages), prolyl hydroxylase (fibroblasts), and CD3 (T cells).Each of the annexins was present in synovial tissues in significant amounts in the three groups studied. Annexin-I was predominantly found within the synovial lining layer and double labelling showed it to be present predominantly in cells of the macrophage lineage. In rheumatoid specimens there was increased staining within the lining layer, perivascularly and on macrophages within the tissue stroma. Annexin-II was present in a distribution similar to that of annexin-I, but with more prominent perivascular staining. Annexins-IV and -VI were seen chiefly in association with areas of lymphocyte infiltration in rheumatoid tissue, whereas annexins-I and -II were absent from these areas. Endothelial cells stained weakly positive for annexins-I and -II, and more strongly for -IV and -VI.This study demonstrates that annexins (particularly annexin-I, a putative mediator of the anti-inflammatory activities of glucocorticoids) are abundant in rheumatoid and non-rheumatoid synovial tissue, annexins-IV and -VI having a distribution distinct from that of -I and -II.
Akt-Mediated Phosphorylation and Activation of Estrogen Receptor α Is Required for Endometrial Neoplastic Transformation in <i>Pten</i>+/− Mice
Authors: Anna Vilgelm, Zenglin Lian, Hong Wang, Stephen L. Beauparlant, Andres Klein-Szanto, Lora Hedrick Ellenson, Antonio Di Cristofano
Journal: Cancer Research (2006)

Abstract PTEN is a tumor suppressor gene frequently mutated in human cancers. In vitro and in vivo studies have shown that PTEN can exert its tumor suppressive function through a variety of mechanisms, including regulation of cell death and cell proliferation. However, it is still unclear which of the many downstream pathways are critical in each different tissue, in vivo. Loss of PTEN is the earliest detectable genetic lesion in the estrogen-related type I (endometrioid) endometrial cancer. Pten+/− mice develop endometrial neoplastic lesions with full penetrance, thus providing a model system to dissect the genetic and biochemical events leading to the transition from normal to hyperplastic and neoplastic endometrial epithelium. Here, we show that loss of Pten in the mouse endometrium activates Akt and results in increased phosphorylation of estrogen receptor α (ERα) on Ser167. ERα phosphorylation results, in turn, in the activation of this nuclear receptor both in vivo and in vitro, even in the absence of ligand, and in its increased ability to activate the transcription of several of its target genes. Strikingly, reduction of endometrial ERα levels and activity dramatically reduces the neoplastic effect of Pten loss in the endometrium, in contrast to complete estrogen depletion. Thus, we provide for the first time in vivo evidence supporting the hypothesis that loss of Pten and subsequent Akt activation result in the activation of ERα-dependent pathways that play a pivotal role in the neoplastic process. (Cancer Res 2006; 66(7): 3375-80)
PHYSICAL EXAMINATION OF THE CEREBRAL PALSIED CHILD
Authors: Russell V. Fuldner
Journal: JAMA (1952)

Within recent years certain medical and lay groups have shown an active increase of interest in the varied problems of children with cerebral palsy. The factors underlying this renewed attention have been outlined elsewhere.1According to the Medical News columns ofThe Journalat least 16 new cerebral palsy centers of permanent character have been established in this country during the past four years. For the most part these facilities are designed for case-finding, diagnosis, and treatment; a few of them have been set up to meet the unusual educational needs of cerebral palsied children. Some states have appropriated special funds to deal with cerebral palsy, and require physicians to report cases to the state health department. A national parents' society,2with objectives in cerebral palsy comparable to those of the National Foundation in the field of infantile paralysis, was founded in 1949. All of this renewed stress
The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT)
Authors: Christian H. Geisler, Arne Kolstad, Anna Laurell, Riikka Räty, Mats Jerkeman, Mikael Eriksson, Marie Nordström, Eva Kimby, Anne Marie Boesen, Herman Nilsson-Ehle, Outi Kuittinen, Grete F. Lauritzsen, Elisabeth Ralfkiær, Mats Ehinger, Christer Sundström, Jan Delabie, Marja-Liisa Karjalainen-Lindsberg, Peter Brown, Erkki Elonen
Journal: Blood (2009)
Expression of the<i>GLI2</i>oncogene and its isoforms in human basal cell carcinoma
Authors: M. Tojo, H. Kiyosawa, K. Iwatsuki, K. Nakamura, F. Kaneko
Journal: British Journal of Dermatology (2003)

Mutations of the patched (Ptc) gene, a developmental regulator implicated in the signalling pathway via sonic hedgehog (Shh) and smoothened (Smo), play an essential pathogenic role in the development of basal cell carcinomas (BCCs). We previously reported the upregulation of Shh signal transducers, including Ptc, Smo and hedgehog-interacting protein, in BCCs. In vertebrates, specific downstream effectors in the Shh signalling pathway include three zinc-finger transcription factors, Gli1, Gli2 and Gli3. Gli1 possesses only an activation domain, while Gli2 and Gli3 contain both activation and repression domains. It remains unclear which of these transcription factors are responsible for the development of BCCs.To examine the expression pattern of Gli2 mRNA by human BCCs in comparison with those by normal human skin and various skin tumours.We performed quantitative reverse transcriptase-polymerase chain reaction analyses with a series of samples from BCCs, other skin tumours and normal skin.We found that Gli2 mRNA expression was enhanced in the BCCs we examined, whereas there was no significant increase in other skin tumours or normal skin. Of four spliced Gli2 isoforms designated Gli2alpha, beta, gamma and delta, the expression of Gli2beta mRNA was increased the most in BCCs.As Gli2beta is an isoform spliced at the first splicing site containing a repression domain and consists of an intact activation domain, its overexpression may lead to the upregulation of the Shh signalling pathway, thereby inducing BCCs.
Comprehensive Evaluation and Rehabilitation of Chronically Ill Ambulatory Patients
Authors: CYNTHIA B. DUTTON
Journal: Annals of Internal Medicine (1968)

A clinic is described that was designed to carry out functional evaluation of patients with chronic medical and psychiatric disabilities and to plan for their vocational rehabilitation. The results obtained in 100 patients evaluated in the clinic during the past 7 years are presented and discussed. Thirty-five of these patients were successfully rehabilitated. Success in rehabilitation varied inversely with the severity of the disability, regardless of specific diagnosis. Statistically significant adverse factors included increasing age, education limited to eighth grade or less, a nonsupportive family environment, unemployment, and dependence upon public welfare assistance. Therefore, assessment of all these factors appears to be essential for effective and efficient rehabilitation planning. Adequate follow-up is necessary to maintain the improvements that have been achieved. Perhaps locating such a clinic in a neighborhood setting would improve the quality of referrals and facilitate follow-up care. The team approach to comprehensive evaluation is readily adaptable for use in outpatient clinics. This approach would permit one responsible physician to be fully and currently informed in regard to all aspects of a given patient's problems and thus to improve greatly the quality and effectiveness of medical care.
GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy
Authors: Mingyue Han, Zhi Yang, Danish Sayed, Minzhen He, Shumin Gao, Lin Lin, Seonghun Yoon, Maha Abdellatif
Journal: Cardiovascular Research (2012)

AimsGATA4 is a transcription factor that is up-regulated during cardiac hypertrophy and plays a fundamental role in myocyte growth and survival. In this study, we investigate the transcriptional vs. post-transcriptional mechanisms that are involved in regulating GATA4 in the heart during neonatal and pressure overload-induced hypertrophic growth.
Finasteride in the treatment of men with androgenetic alopecia
Authors: Keith D. Kaufman, Elise A. Olsen, David Whiting, Ronald Savin, Richard DeVillez, Wilma Bergfeld, Vera H. Price, Dominique Van Neste, Janet L. Roberts, Maria Hordinsky, Jerry Shapiro, Bruce Binkowitz, Glenn J. Gormley
Journal: Journal of the American Academy of Dermatology (1998)
Physical Effects of Increased Venous and Extrarenal Pressure on Renal Vascular Resistance
Authors: WILLIAM H. WAUGH, WILLIAM F. HAMILTON
Journal: Circulation Research (1958)

The oil perfused kidney preparation was used to determine the passive effects of increased venous and extrarenal pressure on renal vascular resistance. The dimensional tube factor of renal resistance varied inversely with the arteriovenous pressure gradient because this pressure difference also determined the pressure difference across the walls of the intrarenal vessels.
Fame is the Spur the Clear Eponym Doth Raise
Authors: Mason G. Robertson
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Scene: First day of rounds with the new house staff, July 1, 1972. Attending: "There's the cause of his swallowing difficulties!" pointing to an x-ray film showing clearly a Zenker's diverticulum. "You there, what do you call that?" Intern: "I just call it a diverticulum, Sir." Attending: "Don't you know its eponym? Who is it named after?" Intern: "I don't believe in eponyms, Sir." Attending: "Thunderation! How do you expect to leave your name in the sands of time?" Intern: "Have you ever heard of anything named after Smith, Sir?" pointing to his name tag: Dr. Jamie Smith. The scene saddened me. As a member of the old school, I have long worshiped the eponym as one of the last vestiges of humanism remaining in an increasingly numeralized and computerized society. Nonetheless, I must concede certain injustices in the scheme. Some have said that those whose names
APPENDICITIS.Read before the Kings County Medical Association, January 12, 1892.
Authors: W. H. BIGGAM
Journal: JAMA (1892)

So many different terms have been applied to the pathological condition, known and described by more modern writers as appendicitis, that one is apt to have a rather confused idea of the subject. My remarks will be confined to a brief description of the pathology, diagnosis and treatment of inflammation of the vermiform appendix, and the tissues surrounding and adjacent to that organ under the comprehensive term of appendicitis, which, it seems to me, as fully and accurately expresses the origin of the lesion, and the pathological condition, as does the term salpingitis in referring to inflammation of the Fallopion tubes, but where, as a result of the original lesion, you might have peritonitis, cellutitis, and ovaritis. So, in appendicitis, you might have following the original lesion, typhlitis or inflammation of the walls of the cæcum; peri-typhlitis, or inflammation of the peritoneum covering the cœcum, or para-typhlitis, inflammation of the
Calcineurin Inhibition Attenuates Mineralocorticoid-Induced Cardiac Hypertrophy
Authors: Yoshiyu Takeda, Takashi Yoneda, Masashi Demura, Mikiya Usukura, Hiroshi Mabuchi
Journal: Circulation (2002)

It remains unclear how mineralocorticoids induce cardiac hypertrophy and fibrosis. Recently, activation of the calcium-dependent phosphatase, calcineurin, has been shown to induce cardiac hypertrophy. In the present study, we examine the role of calcineurin in mineralocorticoid-induced cardiac hypertrophy and fibrosis.Uninephrectomized Wistar-Kyoto rats were placed on a 1.0% NaCl diet and treated with aldosterone (0.75 microg x h(-1)) for 6 weeks with or without the calcineurin inhibitors, FK506 (0.5 mg x kg(-1) x d(-1)) or cyclosporine A (10 mg x kg(-1) x d(-1)). The effect of the angiotensin II type 1 receptor antagonist, losartan (10 mg x kg(-1) x d(-1))on aldosterone-induced cardiac hypertrophy was also studied. Treatment with aldosterone increased the heart weight/body weight ratio, cardiomyocyte size, and collagen amount. The expression of mRNA of both type-III collagen and atrial natriuretic peptide in the heart were increased by aldosterone administration. Both calcineurin activity and its mRNA expression were also increased in aldosterone-induced hypertrophic heart. Treatment with losartan, FK506, or cyclosporine partially prevented aldosterone-induced cardiac hypertrophy and fibrosis.These results suggest that calcineurin is involved in the development of cardiac hypertrophy and fibrosis induced by mineralocorticoid excess. Inhibition of calcineurin may therefore prevent cardiac hypertrophy and fibrosis in mineralocorticoid hypertension.
Adenosine increases sympathetic nerve traffic in humans.
Authors: I Biaggioni, T J Killian, R Mosqueda-Garcia, R M Robertson, D Robertson
Journal: Circulation (1991)

BACKGROUND Adenosine is an effective hypotensive agent in experimental animals and in anesthetized patients, producing little if any evidence of reflex sympathetic activation. In contrast, adenosine increases systolic blood pressure and heart rate in conscious subjects. To determine whether this response is related to sympathetic activation, we studied the cardiovascular and respiratory effects of adenosine in normal subjects while measuring muscle sympathetic nerve traffic through direct recordings from a peroneal nerve. METHODS AND RESULTS Adenosine (80 micrograms/kg/min i.v.) increased heart rate (+32 +/- 3 beats/min), systolic blood pressure (+10 +/- 2 mm Hg), and minute ventilation (+7 +/- 1 l/min). This was accompanied by a dose-dependent increase in muscle sympathetic nerve activity (from 198 +/- 52 to 451 +/- 92 units/min). Adenosine also produced a small, but consistent, decrease in diastolic blood pressure (-6 +/- 3 mm Hg). Adenosine produced a greater increase in sympathetic nerve traffic (145 +/- 32% above baseline) than did nitroprusside (65 +/- 16%) at doses that resulted in equivalent decreased in diastolic blood pressure. Arterial baroreceptor unloading, therefore, could not totally explain the increase in sympathetic traffic produced by adenosine. CONCLUSIONS Given the constellation of findings of increased ventilation and sympathetic activity, we, therefore, propose that adenosine increases sympathetic tone by activating afferent nerves, including arterial chemoreceptors. Contrary to the known inhibitory actions of adenosine on central and peripheral efferent systems, this and other reports suggest that adenosine-induced activation of afferent nerves, leading to sympathetic activation, may be a more widespread phenomenon than previously recognized.
Cross-reacting and species-specific determinants on a major allergen from Dermatophagoides pteronyssinus and D. farinae: Development of a radioimmunoassay for antigen P1 equivalent in house dust and dust mite extracts
Authors: T.A.E. Platts-Mills, P.W. Heymann, M.D. Chapman, M.L. Hayden, S.R. Wilkins
Journal: Journal of Allergy and Clinical Immunology (1986)
Ask, and It Shall be Given You
Authors: Theodore B. Schwartz
Journal: Annals of Internal Medicine (1994)

On Being a Doctor1 September 1994Ask, and It Shall be Given YouTheodore B. Schwartz, MDTheodore B. Schwartz, MD4820 Roberts Road; Boise, ID 83705Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-5-199409010-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail These days, with "managed competition" and "cost control" reverberating in our ears, we must remind ourselves that the modern practice of what I call restorative medicine must often rely heavily on laboratory procedures, frequently expensive, for diagnosis and treatment. For example, experts now insist that the specific cause of Cushing syndrome can no longer be firmly established without catheterization of both petrosal sinuses, usually accompanied by measurement of the response of plasma ACTH to corticotropin-releasing hormone. Big money.There is another less obvious but no less worrisome consequence of the emergence of laboratory data as the major determinant of the ... Author, Article, and Disclosure InformationAuthors: Theodore B. Schwartz, MDAffiliations: 4820 Roberts Road; Boise, ID 83705Corresponding Author: Theodore B. Schwartz, MD, 4820 Roberts Road, Boise, ID 82705. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA Revival of Paul Dudley WhiteBedside Science Reduces Laboratory Art 1 September 1994Volume 121, Issue 5Page: 376KeywordsAdrenocorticotropic hormoneBlood plasmaCatheterizationChartsHormonesResearch laboratoriesThoraxUrine ePublished: 15 August 2000 Issue Published: 1 September 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Laboratory Diagnosis of Kidney Diseases
Authors: Carl F. Anderson
Journal: JAMA (1970)

This book contains the edited proceedings of a seminar held during November 1967. Each of the book's 50 chapters is, in fact, a separate paper. Of the 1,595 references, only 23 are dated later than 1967. Several papers are exceptionally well written. These deal with identification of urinary pigments, the differentiation of hemoglobinuria and myoglobinuria, urine and serum proteins, acute renal failure, primary glomerular disease, and renal complications of diabetes mellitus. Other well-written papers describe microdissection of the nephron, urinary calculi, drug-induced nephropathy, immunopathogenesis of renal disease, and the association between renal and liver disease. There is a genuine need for a book to describe current laboratory methods and integrate the results obtained with historical, physical and roentgenographic findings. I had hoped this book would fill the void, but it does not. The compilation of separate papers without integrating discussions or summaries does not achieve a systematic cohesive description of
DNA-dependent protein kinase (DNA-PK) permits vascular smooth muscle cell proliferation through phosphorylation of the orphan nuclear receptor NOR1
Authors: Senad Medunjanin, Jan-Marcus Daniel, Sönke Weinert, Jochen Dutzmann, Frank Burgbacher, Sarah Brecht, Dennis Bruemmer, Thilo Kähne, Michael Naumann, Daniel G Sedding, Werner Zuschratter, Ruediger C Braun-Dullaeus
Journal: Cardiovascular Research (2015)

Being central part of the DNA repair machinery, DNA-dependent protein kinase (DNA-PK) seems to be involved in other signalling processes, as well. NOR1 is a member of the NR4A subfamily of nuclear receptors, which plays a central role in vascular smooth muscle cell (SMC) proliferation and in vascular proliferative processes. We determined putative phosphorylation sites of NDA-PK in NOR1 and hypothesized that the enzyme is able to modulate NOR1 signalling and, this way, proliferation of SMC.Cultured human aortic SMC were treated with the specific DNA-PK inhibitor NU7026 (or siRNA), which resulted in a 70% inhibition of FCS-induced proliferation as measured by BrdU incorporation. Furthermore, FCS-stimulated up-regulation of NOR1 protein as well as the cell-cycle promoting proteins proliferating cell nuclear antigen (PCNA), cyclin D1, and hyperphosphorylation of the retinoblastoma protein were prevented by DNA-PK inhibition. Co-immunoprecipitation studies from VSM cell lysates demonstrated that DNA-PK forms a complex with NOR1. Mutational analysis and kinase assays demonstrated that NOR1 is a substrate of DNA-PK and is phosphorylated in the N-terminal domain. Phosphorylation resulted in post-transcriptional stabilization of the protein through prevention of its ubiquitination. Active DNA-PK and NOR1 were found predominantly expressed within the neointima of human atherosclerotic tissue specimens. In mice, inhibition of DNA-PK significantly attenuated neointimal lesion size 3 weeks after wire-injury.DNA-PK directly phosphorylates NOR-1 and, this way, modulates SMC proliferation. These data add to our understanding of vascular remodelling processes and opens new avenues for treatment of vascular proliferative diseases.