tbuckley/cabot-search huggingface dataset:
Abstract 2337: Effect of embryonic stem (ES) cell-conditioned microenvironment on the reprogramming of human cancer
Authors: Myoung Ok Kim, Yong-Yeon Cho, Sung-Hyun Kim, Chul-Ho Jeong, Kun-Yeong Lee, Young-Jin Jeon, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2010)

Abstract During embryonic development, the extracellular matrix (ECM) plays a critical role in the regulation of stem cells to different lineages, cell migration and proliferation. A recently developed 3-dimensional (3D) ES-conditioned matrigel matrix culture of metastatic melanoma cells induces reprogramming and differentiation. However, although the ES-cell conditioned microenvironment induces melanoma cell reprogramming to suppress invasive behavior, the mechanisms have not yet been clearly understood. To investigate the effect of the cancer cell microenvironment, we hypothesized that 1) the microenvironment might induce nuclear reprogramming; 2) microenvironment-induced reprogramming might affect cell proliferation; 3) microenvironment-induced reprogramming might induce differentiation-mediated cellular senescence; and 4) microenvironment-induced reprogramming causes a loss of anchorage-independent cell growth, which is a hallmark of cancer cell properties. Here, we found that the ES-conditioned 3D-microenvironment induced a dramatic change in the morphology of A431 human skin epidermoid carcinoma cells and SK-MEL-28 human skin malignant melanoma cells. In the anchorage-independent cell growth assay, we found that A431 and SK-MEL-28 cells grown in the 3D ES-conditioned microenvironment exhibited dramatically decreased colony growth in soft agar. Real time PCR analysis indicated that ES-conditioned microenvironment suppressed endogenous Oct4 and Nanog gene expression in A431 and SK-MEL-28 cells and inhibited c-jun and c-fos promoter activities, which are components of the AP-1 transcriptional factor complex. Very importantly, we found that the ES cell-conditioned microenvironment inhibited telomerase activity, resulting in the induction of cellular senescence in human skin melanoma cells. We found that ES-conditioned medium contained a greater amount of Gremlin, a natural inhibitor of TGF-β signaling. Gremlin treatment of A431 and SK-MEL-28 cells induced morphological changes as observed in the 3D ES-conditioned matrigel matrix. Our results demonstrated that the ES-cell conditioned microenvironment inhibited proliferation and induced cellular senescence of A431 and SK-Mel-28 cells through the inhibition of TGF-β signaling by Gremlin. Furthermore, our data strongly suggests that modulation of TGF-β signaling in the cancer microenvironment is a potential strategy to modulate cancer cell behaviors and properties. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2337.
Abstract 3455: p53 status determines the radio-sensitizing effect of an Akt kinase inhibitor in malignant gliomas
Authors: Disha R. Patel, Nicolaus Gordon, Arnab Chakravarti, Kamalakannan Palanichamy
Journal: Cancer Research (2012)

Abstract Purpose: It has been reported that PI3K-Akt pathway, which plays a role in cell survival and apoptosis, is deregulated in many cancer types. In gliomas, amplification and constitutive activation of Akt, which can result from amplifications in TKIs including EGFR, IGFR1α, PDGFRα, etc. and mutations in PI3K, PTEN, etc. are thought to play a role in radiation resistance. Some have tried to modulate the PI3K/Akt pathway by targeting molecules upstream of Akt such as Ras and PI3K, while others have used inhibitors targeting molecules downstream of Akt, such as mTOR. These inhibitors have been shown to reduce cancer cell growth in vitro and in vivo, but have had limited success in clinical settings as single agents. In our study, we have investigated the use of a phosphatidylinositol ether lipid analogue (PIA) that directly inhibits Akt activation as a radiosensitizer for GBM. Materials and Methods: We utilized multiple established (U87, LN18, LN229) and primary (VC3, MGH8, OSU61) cell lines with varying molecular and genetic signatures to determine radiosensitizing effects of PIA. We performed Annexin V, clonogenic survival, and COMET assays on glioma cells treated with PIA, radiation (RT), and a combination of PIA and RT. Western blot was performed using these cell lines to examine the changes in expression of PI3K-Akt pathway, apoptotic, and pro-survival proteins following treatment. Furthermore, we sequenced tumor suppressor genes p53 and PTEN in all cell lines used in this study. Gene silencing of p53 was done in U87 cells via a lentiviral transfection of shRNA. Results and Conclusions: PIA decreases the activation of Akt to a considerable extent (∼80%), induces apoptosis, and reduces clonogenicity of all cell lines tested. A subset of cell lines did show enhanced radiosensitization when PIA is combined with RT. Further detailed investigation of differential radiosensitizing effects led us to discover the link between p53 status, Akt kinase inhibition, and radiosensitization. GBMs with intact p53 had no radiosensitizing effect after Akt kinase inhibition, whereas radiosensitization was observed if either p53 is null or mutated. This observation was further validated using isogenic U87 p53 knockdown cells. Surprisingly, MGMT status, a predictive marker of outcome in GBM, did not determine radiosensitizing effects of PIA in the GBM cells tested. Through this preclinical study, we have identified which subset of GBM patients will derive benefit from Akt kinase inhibition and the investigations conducted justify future clinical trials and lays ground work for phase I study. 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 3455. doi:1538-7445.AM2012-3455
Amar Dhillon replies to "Pathology reports solve 'new bowel disease' riddle"
Authors: A. Dhillon
Journal: BMJ (2011)

The reappearance of some of my histology grading sheets for the Wakefield study is interesting.1 2 I have not seen them since 1997-8, when I gave them to Andy Wakefield. The BMJ ’s articles on these grading sheets in the issue of 12 November show several misunderstandings.3 Many are a result of a lack of understanding of the difference between, on the one hand, the systematic documentation of specific microscopical features in a grading sheet by a “blinded” pathologist and, on the other, conclusion of an overall clinicopathological diagnosis by integrating clinical information with diverse lines of investigation. The difference between the two activities should be understood better.

Routine diagnostic histopathology is done with knowledge of an individual patient’s clinical details at the time of diagnostic reporting, so rendering a diagnostic histopathological opinion is usual and appropriate (in direct contrast to a blinded research review). The perceived clinical significance of microscopic observations may change as …
Preparation, physico-chemical and pharmacokinetic characterization of monomethoxypoly(ethylene glycol)-derivatized superoxide dismutase
Authors: Francesco M. Veronese, Paolo Caliceti, Antonio Pastorino, Oddone Schiavon, Luciana Sartore, Lucia Banci, Luigi Monsu Scolaro
Journal: Journal of Controlled Release (1989)
Hemodynamic Effects of Dopamine in the Dog Before and After Alpha Adrenergic Blockade
Authors: JOHN L. MCNOY, LEON I. GOLDBERG
Journal: Circulation Research (1966)

Dopamine reacts with blood vessel receptors, causing both dilatation and constriction. In the dog the vasodilator receptors are presentin the renal and mesenteric vascular beds but absent from the vascular beds of the limb. The vasoconstrictor receptors, alpha adrenergic in type, are present in both somatic and visceral regions. The net effect of intravenously administered dopamine on regional flows will depend on the relative intensity of these opposing effects and on changes in blood pressure. The present study was an attempt to evaluate the significance of the vasoconstrictor action of dopamine infused at nonpressor doses, i.e., 3 to 6 µg/kg/min. Renal and femoral blood flows were measured simultaneously, and systemic hemodynamics were evaluated before and after administration of the alpha adrenergic antagonists, phentolamine and phenoxybenzamine. The results indicate that the vasoconstrictor property of dopamine is masking a mild depressor effect, ranging in magnitude from 10 to 25 mm Hg. Dopamine increases cardiac output independently of its alpha adrenergic properties. Dopamine causes an increase in renal blood flow of equal magnitude before and after alpha adrenergic block but reduces renal vascular resistance to a lower level after alpha block, reflecting the depression in blood pressure. Dopamine does not alter femoral vascular resistance either before or after alpha adrenergic block. However, femoral blood flow is decreased by dopamine after alpha block, secondary to the depression of blood pressure. It is concluded that under the conditions of these studies, alpha adrenergic block enhances the vasodepressor property of dopamine and does not appreciably modify its ability to increase cardiac output and redistribute peripheral blood flow.
Heart disease rising in central and eastern Europe
Authors: R. Watson
Journal: BMJ (2000)

Europe's policymakers are being asked to make improvements in cardiovascular health a major political priority as evidence emerges of the spread of heart disease across social and geographical boundaries.

Cardiovascular disease is already the cause of four million deaths a year in Europe. Mortality from the disease is rising in central and eastern Europe, where it is almost double that of the worst affected countries in the European Union. On current trends, the disease will be responsible for 19 million deaths annually worldwide by 2020.

The Winning Hearts campaign to move heart disease higher up the political agenda was launched this week by the British Heart Foundation and the European Society of Cardiology. Their aim is to ensure that every child born in …
NARRATION
Authors: Louis Pelner
Journal: JAMA (1970)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Expression of vascular endothelial growth factor in normal pituitary cells and pituitary adenomas producing adrenocorticotropic hormone
Authors: Takashi Yamamoto, Yasuko Nishizawa, Motomu Tsuji, Youichi Saitoh, Hiroko Funai, Tatsuya Hirai, Ayako Sugihara, Tohru Tsujimura, Yasuo Nakata, Shingo Ishiguro, Nobuyuki Terada
Journal: Endocrine Pathology (1999)
Src tyrosine kinase inhibition prevents pulmonary ischemia–reperfusion-induced acute lung injury
Authors: Takeshi Oyaizu, Shan-Yu Fung, Atsushi Shiozaki, Zehong Guan, Qiao Zhang, Claudia C. dos Santos, Bing Han, Marco Mura, Shaf Keshavjee, Mingyao Liu
Journal: Intensive Care Medicine (2012)
Mental Illness, Due Process and the Criminal Defendant
Authors: Martin Lipp
Journal: JAMA (1968)

The problems discussed here make this an important book. Explicitly, the authors recommend changes in New York state law dealing with reputedly mentally ill persons who have been indicted or convicted or sentenced because of alleged criminal behavior. Implicitly, this document indicts the unbelievably antiquated, inequitable, and often senseless statutes which deal with such problems in all our states. This substantial task is undertaken by "The Special Committee on the Study of Commitment Procedures and the Law Relating to Incompetents" of the New York city bar, together with Fordham Law School. The perspective and terminology are primarily those of the legal profession, but physicians should not be deterred from reading the book. We in medicine bear the primary responsibility for commitment of patients into mental hospitals, and sometimes this amounts to virtual imprisonment without due process. This, often true in civil commitments, may reach tragic proportions with real or alleged
Efficacy of Inactivated Vaccine in Preventing Antigenically Drifted Influenza Type A and Well-Matched Type B
Authors: Norio Sugaya
Journal: JAMA (1994)

To evaluate the efficacy of currently used inactivated influenza vaccine during a severe epidemic caused by antigenically drifted influenza type A(H3N2) and well-matched type B viruses during the 1992-1993 season.Prospective nonrandomized controlled trial.An urban general hospital pediatric asthma clinic in Japan.A total of 137 children with moderate to severe asthma (mean age, 7.0 years; range, 2 to 14 years).Eighty-five children received trivalent split-antigen vaccine containing A/Beijing/352/89 (H3N2) and B/Bangkok/163/90 (B/Panama/45/90-like strain). Fifty-two were unvaccinated.Protection against infection was determined using hemagglutination inhibition test and virus isolation. Clinical efficacy was estimated based on febrile episodes with antibody rise or virus isolation.Although marked antigenic drift in hemagglutinin was demonstrated in the epidemic virus (A/Beijing/32/92-like strain), the protection against influenza type A(H3N2) infection was 67.5% (P < .01). The protection against influenza type B infection was 43.7% (P < .01), although the epidemic influenza type B viruses were antigenically almost identical to the vaccine strain. Inactivated vaccine was not effective for protection against influenza type B infection in children younger than 7 years. High clinical effectiveness was demonstrated in children at least 7 years of age during the epidemic.Our data suggest that current inactivated vaccine is highly effective for protection against influenza type A(H3N2) virus infection regardless of antigenic drift. In contrast, the protective efficacy obtained by vaccination may not be sufficient against influenza type B virus infection, and especially in young children, it does not offer protection.
Relationships between C3b receptor (CR1) activity of erythrocytes and positive Coombs' tests.
Authors: Y Inada, M Kamiyama, T Kanemitsu, W S Clark, Y Asai
Journal: Annals of the Rheumatic Diseases (1986)

Although positive direct Coombs9 tests occur in most patients with active systemic lupus erythematosus (SLE), haemolytic anaemic associated with antibody to erythrocytes (E) occurs in less than 10%. Our studies show an association between positive direct Coombs9 tests and both the presence of circulating immune complexes and diminished activity of the C3b receptor (CR1) of E. Data presented in this report suggest that in vivo binding of immune complexes and complement by the CR1 of E results in positive direct Coombs9 tests in the absence of antibody to E. These observations explain the low frequency of haemolytic anaemia compared with the high frequency of direct positive Coombs9 tests in patients with SLE.
Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery
Authors: Jay L. Koyner, Michael R. Bennett, Elaine M. Worcester, Qing Ma, Jai Raman, Valluvan Jeevanandam, Kristen E. Kasza, Michael F. O'Connor, David J. Konczal, Sharon Trevino, Prasad Devarajan, Patrick T. Murray
Journal: Kidney International (2008)
Clinical and Endoscopic Aspects of Tumors of the Ampulla of Vater
Authors: M.V. Sivak
Journal: Endoscopy (1988)

Diverse tumors may arise at the ampulla of Vater, although the clinical manifestations for all types of lesions are similar. Carcinoma and benign adenomas are the most important ampullary tumors, and there is evidence that adenomas are premalignant. Endoscopy offers the best prospect of accurate diagnosis, but the sensitivity and specificity of this diagnostic modality is less than expected. In particular, endoscopic biopsies may be falsely negative for carcinoma in a significant percentage of cases. When successful, ERCP may demonstrate dilated pancreatic and bile ducts and in some cases the presence of a tumor mass. The preferred treatment for virtually all ampullary tumors is surgery, the general types of operation being local resection, pancreatoduodenectomy, and biliary decompression procedures. The choice of operation depends on whether the tumor is benign or malignant, its extent, especially if malignant, and an assessment of the patient's ability to withstand radical resection. Although the operative morbidity and mortality is lower for local excision in comparison to pancreatoduodenectomy, there is a greater chance for recurrence of malignant and premalignant neoplasms when the tumor is locally excised.
Multiple cutaneous, oropharyngeal and pulmonary nodules
Authors: O. Veraitch, K. Bhargava, B. Moriarty, E. Calonje, R. Mallipeddi, S. Whittaker
Journal: British Journal of Dermatology (2015)

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis defined by heterogeneous multiorgan involvement. Due to the rarity of this disease strong evidence-based therapies have yet to be established and prognosis has previously been considered to be poor, with more than half of patients dying within 3 years of initial presentation. We describe an 86-year-old woman with a 34-year history of extensive cutaneous and internal nodules with typical pathological and immunophenotypical (CD68(+) /CD1a(-) ) features of ECD without evidence of the BRAF V600E mutation. The cosmetic appearance of cutaneous nodules and hoarse voice caused by vocal cord nodules has been managed surgically. More aggressive therapies reported for ECD were trialled for this patient, such as radiotherapy and interferon-α, with no response. This case demonstrates a relatively good prognosis in ECD that has been managed conservatively.
Mycobacteria from aquaria.
Authors: T Mansson
Journal: BMJ (1970)

BRNAL nearer to that of 15 mg. of morphine sulphate (11-4 mg. of anhydrous morphine).Our own studies* have shown that 13-3 mg. of morDhine sulohate contains the same amount of anhydrous morphine as 20 mg. of papaveretum, and that the effect of these two are indistinguishable clinically.-Weare, etc.,
Effects of glucocorticoids and mineralocorticoids on proliferation and maturation of human peripheral blood stem cells
Authors: St�phanie Grafte-Faure, Catherine Leveque, Marc Vasse, Claudine Soria, Vic Norris, Jean-Pierre Vannier
Journal: American Journal of Hematology (1999)

It has been shown that hematopoietic progenitors can be expanded ex vivo in the presence of various cytokine combinations. Glucocorticoids (GC) are involved in the self-renewal of erythroid progenitors in chicken. To see whether GC have a similar effect on hematopoiesis in humans, CD34+ peripheral blood stem cells were cultured in serum free medium in the presence of a GC, triamcinolone acetonide. However, our results demonstrate an inhibition of both erythroid and granulocyte-macrophage (GM) proliferation and a modification of erythroid colony morphology. Furthermore, RU38486 (Mifepristone), a potent GC antagonist, was unable to reverse the inhibitory effect of triamcinolone acetonide. We also identified and characterized another steroid subfamily, the mineralocorticoid (MC) subfamily, in human PB CD34+ cells. The MC, aldosterone, significantly enhanced GM colony formation and diminished the erythroid colony number. Neither of effects were inhibited by ZK91587, an antagonist specific to the MC receptor (MCR). In contrast, ZK91587 reversed the stimulatory effect of deoxycorticosterone on GM colony formation. Cytoplasmic staining for MCR was observed in CD34+ cells incubated with a polyclonal antiserum raised against human MCR. To our knowledge, this is the first demonstration of the presence of MCR in human PB CD34+ cells. Am. J. Hematol. 62:65–73, 1999. © 1999 Wiley-Liss, Inc.
1147 CAROTID INTIMA-MEDIA THICKNESS IS INCREASED IN FATTY LIVER PATIENTS EVEN IF NOT INCLUDED IN NON-ALCOHOLIC FATTY LIVER DISEASE
Authors: Jeong Han Kim, H.J. Yim, E.L. Yoon, H.J. Lee, Y.S. Lee, E.S. Jung, Ji Hoon Kim, J.E. Yeon, K.S. Byun, S.H. Um
Journal: Journal of Hepatology (2010)
Commentary: The legal position
Authors: M. A Jones
Journal: BMJ (1995)

The case presented by John Mitchell raises several important legal issues.1 By far the most important in the context of the law on consent to medical treatment is the role of the medical profession in setting the parameters of consent. In the tort of negligence the Bolam test provides that a doctor who conforms with a practice accepted as proper by a responsible body of professional opinion is not negligent, allowing always for the possibility that there may be more than one responsible body of professional opinion.2 In general terms it is possible to say that it is the profession which effectively sets the standard of competence required by law.

The law on consent to treatment should be distinguished, however, from the law of negligence. Any treatment that entails the physical touching of a competent adult patient without consent constitutes the tort of battery. Consent provides a defence which makes the touching lawful. With consent involving a competent adult the simple question from the lawyer's perspective is, did the patient in fact consent to the procedure? It is important to note that the question is not, did a …
An 11-item index predicted 5-year and 9-year mortality in community-dwelling elderly adults
Authors: William J. Hall
Journal: Annals of Internal Medicine (2012)

Source Citation Schonberg MA, Davis RB, McCarthy EP, Marcantonio ER. External validation of an index to predict up to 9-year mortality of community-dwelling adults aged 65 and older. J Am Geriatr Soc. 2011;59:1444-51. 21797837