tbuckley/cabot-search huggingface dataset:
Abstract 5308: Id-1 gene and protein as novel therapeutic targets for metastatic cancer
Authors: Ryuichi Murase, Chandani Limbad, Rumi Murase, Liliana Soroceanu, Sean McAllister, Pierre Yves Desprez
Journal: Cancer Research (2012)

Abstract During normal development and embryogenesis, helix-loop-helix Id proteins regulate the differentiation programs of many tissues. Moreover, recent studies have shown that dysregulated Id expression contributes to cancer progression and metastasis. Specifically, we found high levels of one of the Id family members, Id-1, in breast, prostate, brain and head and neck tumor cells which were highly aggressive, and low levels of Id-1 in non-invasive tumor cells. Ectopic expression of Id-1 in non-aggressive human cancer cells rendered them highly proliferative and invasive, and induced high levels of matrix metalloproteinase (MMP) expression. Conversely, human metastatic cancer cells became significantly less proliferative and invasive in culture when Id-1 protein expression was decreased by antisense RNA or shRNA directed against the Id-1 gene. Next, we asked whether Id-1 could be exploited as a therapeutic target to treat metastatic cancers. Using tumor-bearing animals and systemic gene targeting technique, we showed that reduction of Id-1 levels, and consequently MMP expression, could significantly decrease the metastatic spread of cancer cells. Further, several molecular pathways underlying Id-1 effects on epithelial to mesenchymal transition (EMT) and neoangiogenesis were also identified in certain types of cancer. These results suggested that Id-1 gene and/or protein could be a promising target for development of therapeutic strategies to reduce cancer metastasis. Since Id-1 expression is scarce in most mature adult tissues, a majority of normal cells would not be affected by systemic therapy targeting this gene. We determined that a cannabinoid compound, CBD, could specifically inhibit the expression of the Id-1 gene and, as a result, cancer cell proliferation and invasion in culture and tumor metastasis in vivo. In tumor-bearing mice, we observed significant anti-metastatic effects after daily treatment with CBD. Id-1 expression in tumor cells from lung foci was significantly down-regulated as well as Ki67, a marker of cell proliferation. Finally, CBD prolonged the survival of tumor-bearing mice even though the treatment was initiated after the establishment of metastases. Overall, our data suggest that Id proteins act as key regulators of tumor metastasis and suggest the use of Id genes as novel therapeutic targets. 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 5308. doi:1538-7445.AM2012-5308
Reviving pegylated interferon as a therapeutic agent for hepatitis D: No more room for nucleos(t)ides?
Authors: Holger H. Lutz, Christian Trautwein, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2011)

Chronic infection with hepatitis B virus and hepatitis delta virus (HDV) results in the most severe form of viral hepatitis. There is no currently approved treatment. We investigated the safety and efficacy of 48 weeks of treatment with peginterferon alfa-2a plus adefovir dipivoxil, peginterferon alfa-2a alone,and adefovir dipivoxil alone.We conducted a randomized trial in which 31 patients with HDV infection received treatment with 180 lg of peginterferon alfa-2a weekly plus 10 mgof adefovir daily, 29 received 180 lg of peginterferon alfa-2a weekly plus placebo, and 30 received 10 mg of adefovir alone weekly for 48 weeks. Follow-up was conducted for an additional 24 weeks. Efficacy end points included clearance of HDV RNA,normalization of alanine aminotransferase levels, and a decline in levels of hepatitis B surface antigen (HBsAg).The primary endpoint—normalization of alanine aminotransferase levels and clearance of HDV RNA at week 48--was achieved in two patients in the group receiving peginterferon alfa-2a plus adefovir and two patients in the group receiving peginterferon alfa-2a plus placebo but in none of the patients in the group receiving adefovir alone. At week 48, the test for HDV RNA was negative in 23% of patients in the first group, 24% of patients in the second, and none of those in the third (P¼ 0.006 for the comparison of the first and third groups; P¼ 0.004 for the comparison of the second and third). The efficacy of peginterferon alfa-2a was sustained for 24 weeks after treatment, with 28% of the patients receiving peginterferon alfa-2a plus adefovir or peginterferon alfa-2a alone having negative results on HDV-RNA tests; none of the patients receiving adefovir alone had negative results. A decline in HBsAg levels of more than 1 log10 IU per milliliter from baseline to week 48 was observed in 10 patients in the first group, 2 in the second, and none in the third (P<0.001 for the comparison of the first and third groups and P¼0.01 for the comparison of the first and second).Treatment with peginterferon alfa-2a for 48 weeks, with or without adefovir, resulted in sustained HDV RNA clearance in about one quarter of patients with HDV infection.
Additives in plastics.
Authors: R D Deanin
Journal: Environmental Health Perspectives (1975)

The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve their processing and end-use performance. In order of total volume used, these monomeric additives may be classified as follows: reinforcing fibers, fillers, and coupling agents; plasticizers; colorants; stabilizers (halogen stabilizers, antioxidants, ultraviolet absorbers, and biological preservatives); processing aids (lubricants, others, and flow controls); flame retardants, peroxides; and antistats. Some information is already available, and much more is needed, on potential toxicity and safe handling of these additives during processing and manufacture of plastics products.
Causality, menopause, and depression: a critical review of the literature
Authors: L. Nicol-Smith
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To assess whether causal criteria can be used to find out whether there is support in published research for maintaining that menopause causes depression. <b>Design</b>: Ninety four articles from 30 years of research examining the relation of natural menopause to depression were traced by using Medline and systematic follow up of reference lists. Specified exclusion and inclusion criteria were applied, and the resulting 43 epidemiological primary research articles were classified and tabulated according to sample and measures used and the researchers9 own conclusion as to whether or not an association had been established. This material was qualitatively evaluated with Hill9s nine criteria for causality. <b>Result</b>: There is insufficient evidence at present to maintain that menopause causes depression. In addition to methodological and statistical problems, a temporal problem in the menopause concept hinders research in this area. <b>Conclusion</b>: Causal criteria can usefully be used to structure a literature review. Further theoretical work is required to integrate standard clinical epidemiological concepts. <h3>Key messages</h3> Causal and methodological criteria can be used to structure the findings and draw conclusions in a literature review Menopause has so far not been shown to cause depression In addition to methodological and statistical constraints, a temporal problem related to the menopause concept hinders research in this area Theoretical work is required to integrate causal criteria and standard clinical epidemiological con- cepts
Update: A 35-Year-Old Physician With Opioid Dependence
Authors: Nadine Farag
Journal: JAMA (2008)

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
Cyclosporine inhibition of calcineurin activity in human leukocytes in vivo is rapidly reversible.
Authors: T D Batiuk, F Pazderka, J Enns, L DeCastro, P F Halloran
Journal: Journal of Clinical Investigation (1995)

Despite increasing information about the mechanism of action of cyclosporine A (CsA), little is known about the way lymphocytes recover from CsA. Recovery is central to understanding the pharmacodynamics of CsA in vivo. We studied the recovery of calcineurin phosphatase (CN) activity in CsA-treated cells. Single dose kinetics in renal transplant patients showed that inhibition of CN activity in PBL increased and fell concomitant with CsA blood vessels. In vitro, control PBL treated with CsA 100 micrograms/l, washed, and resuspended in CsA-free medium showed little recovery (0-20%) after 24 h. Erythrocytes or anti-CsA Ab added to the recovery medium increased recovery to 50% within 4 h. Similar recovery was seen in the ability of cells to produce IFN-gamma after OKT3 stimulation. Recovery of CN activity was associated with the efflux of [3H]CsA, was not blocked by cycloheximide and was temperature sensitive. A cell line with high expression of surface P glycoprotein (PGP), showed rapid recovery. However, PGP blockade did not prevent recovery in PBL, indicating a different PGP-independent mechanism. In PBL, recovery from CsA is slow and limited in vitro, but rapid in vivo, where CsA equilibrates among a complex set of extralymphocytic binding sites.
Folliculitis decalvans including tufted folliculitis: clinical, histological and therapeutic findings
Authors: None POWELL, None DAWBER, None GATTER
Journal: British Journal of Dermatology (1999)

In a series of 18 patients with folliculitis decalvans attending the Oxford hair clinic, eight were found to have areas of tufted folliculitis either at presentation or follow-up. There was no difference between these two groups in their presentation, clinical course, growth of causative organism (Staphylococcus aureus) or investigations including histology. We suggest that these two entities form part of a spectrum of a single disease. We performed lymphocyte staining on affected scalp biopsies, including CD4: CD8 and T-cell/B-cell ratios, but found no evidence of local immune suppression or failure which would explain the abnormal host response to a common pathogen in this rare condition. We introduced a new treatment regimen for these patients, oral rifampicin and oral clindamycin together for 10 weeks. Ten of the 18 patients have responded well with no evidence of recurrence 2-22 months after one course of treatment, and 15 of the 18 responded after two or three courses.
Defining the pathogenic involvement of desmoglein 4 in pemphigus and staphylococcal scalded skin syndrome
Authors: Takeshi Nagasaka, Koji Nishifuji, Takayuki Ota, Neil V. Whittock, Masayuki Amagai
Journal: Journal of Clinical Investigation (2004)

Desmogleins (Dsgs), cadherin-type cell adhesion molecules, are targeted in skin-blistering diseases such as pemphigus and staphylococcal scalded skin syndrome (SSSS). The role of Dsg4, a new isoform, was investigated in these diseases. Dsg4 was recognized by 30 (77%) of 39 pemphigus sera containing anti-Dsg1 IgG but not by 16 pemphigus sera containing no anti-Dsg1 IgG or by 34 normal control sera. The Dsg4 immunoreactivity of these sera was abolished by removal of anti-Dsg1 IgG. Conversely, the removal of anti-Dsg4 IgG from pemphigus sera reduced the immunoreactivity against Dsg1 only 13.8% ± 8.8% (n = 23) and did not affect its ability to induce blisters in neonatal mice. IgG that was affinity-purified on Dsg4 recognized Dsg1 but failed to induce blisters, while IgG purified on Dsg1 from the same pemphigus foliaceus sera induced blisters. Thus, pemphigus sera show Dsg4 reactivity due to cross-reactivity of a subset of anti-Dsg1 IgG, and the Dsg4/Dsg1–cross-reacting IgG has no demonstrable pathogenic effect. In addition, Dsg4 was not cleaved by exfoliative toxins that induce blisters in SSSS. These findings suggest that Dsg4 may play a role other than adhesion and that the cross-reactivity of desmoglein autoantibodies should be factored into the framework of future studies of autoimmune mechanisms in pemphigus.
Comparative Longevity of Christian Scientists
Authors: Rita Swan
Journal: JAMA (1990)

<h3>To the Editor.—</h3> We appreciate your publishing the study by Dr Simpson<sup>1</sup>on Christian Scientists' mortality rates. The study is particularly timely because recently the Christian Science church claims to have developed data indicating that Christian Science is twice as effective as medical science at healing all diseases of children (<i>Los Angeles Times</i>. June 27, 1989:1;<i>San Francisco Banner Daily Journal</i>. May 31, 1989:3). The church is currently presenting its data to state legislatures in an effort to get Christian Science treatment established as a legal substitute for the medical care needed by sick children. In the past, legislatures have given the Christian Science church virtually everything it asks for. We strongly urge the medical profession to challenge the church's legislative strategies and save the lives of children.
US healthcare falls further behind that of other industrialised countries
Authors: B. Roehr
Journal: BMJ (2011)

Healthcare in the United States continued to deteriorate in quality, accessibility, and affordability in the period immediately leading up to enactment of major reforms, the Affordable Care Act of 2010.

The nation slipped in absolute terms from a score of 67 (of a possible 100) in 2006 to 64 in 2009, according to the latest National Scorecard. The analysis was released by the Commonwealth Fund Commission on a High Performance Health System at a news conference in Washington, DC, on 18 October.

On the core indicators of potentially preventable deaths before age 75, such as cancers that can be screened for, diabetes, bacterial infections, and childhood infectious diseases, the US has improved, “but …
Implications of sex hormone levels in the intrapulmonary vasodilatation in cirrhosis
Authors: R. Aller, C.M. Fernández-Rodriguez, D.A. de Luis, J.L. Lledó, J.L. Moya, S. Avila, J. Villar, V. Moreira, D. Boixeda
Journal: Journal of Hepatology (2000)
Unsuspected Diabetes Mellitus in Peripheral Vascular Disease
Authors: Carl C. Bartels, Fiore R. Rullo
Journal: New England Journal of Medicine (1958)

THE association of peripheral vascular disease with diabetes mellitus has been so well verified that it is now an established fact, but less well recognized is the frequency of abnormal glucose tolerance occurring with verified peripheral vascular disease in the patient who has had no previous evidence of diabetes mellitus.Lukens,1 in 1952, stated that arteriosclerosis of the feet may appear before glycosuria and is most common at the age when diabetes is most likely to occur.In 1955 Wilkerson and his co-workers2 called attention to the frequency of laboratory evidence of diabetes mellitus in patients with gangrene of the . . .
Treatment Decisions About Cholesterol: What About Smoking?-Reply
Authors: Wendy Borow
Journal: JAMA (1992)

<h3>In Reply.</h3> —The American Medical Association launched the Fat/Cholesterol Education Program, formerly the Campaign Against Cholesterol, in January 1988. All of the information generated by the Campaign follows the NCEP guidelines. The brochure referred to in Dr Lutschg's letter, entitled "What You Should Know About High Blood Cholesterol," should have been updated at the last printing to reflect the NCEP data. We regret the error, and will ensure that the change will be made when the brochure is printed again.
Inferring Parameters Shaping Amino Acid Usage in Prokaryotic Genomes via Bayesian MCMC Methods
Authors: Hugo Naya, Daniel Gianola, Héctor Romero, Jorge I. Urioste, Héctor Musto
Journal: Molecular Biology and Evolution (2005)

Molar content of guanine plus cytosine (G + C) and optimal growth temperature (OGT) are main factors characterizing the frequency distribution of amino acids in prokaryotes. Previous work, using multivariate exploratory methods, has emphasized ascertainment of biological factors underlying variability between genomes, but the strength of each identified factor on amino acid content has not been quantified. We combine the flexibility of the phylogenetic mixed model (PMM) with the power of Bayesian inference via Markov Chain Monte Carlo (MCMC) methods, to obtain a novel evolutionary picture of amino acid usage in prokaryotic genomes. We implement a Bayesian PMM which incorporates the feature that evolutionary history makes observed data interdependent. As in previous studies with PMM, we present a variance partition; however, attention is also given to the posterior distribution of “systematic effects” that may shed light about the relative importance of and relationships between evolutionary forces acting at the genomic level. In particular, we analyzed influences of G + C, OGT, and respiratory metabolism. Estimates of G + C effects were significant for amino acids coded by G + C or molar content of adenine plus thymine (A + T) in first and second bases. OGT had an important effect on 12 amino acids, probably reflecting complex patterns of protein modifications, to cope with varying environments. The effect of respiratory metabolism was less clear, probably due to the already reported association of G + C with aerobic metabolism. A “heritability” parameter was always high and significant, reinforcing the importance of accommodating phylogenetic relationships in these analyses. “Heritable” component correlations displayed a pattern that tended to cluster “pure” G + C (A + T) in first and second codon positions, suggesting an inherited departure from linear regression on G + C.
Age-related changes in the transmembrane potential of isolated rabbit sino-atrial nodes and atria
Authors: N. TODA
Journal: Cardiovascular Research (1980)

Transmembrane potentials were recorded from single cells of the sino-atrial (S-A) node and right atrium isolated from rabbits of different ages (2 to 360 days old). In neonatal rabbit atria, the shape of pacemaker action potentials recorded from same S-A nodal cells were not regular, and action potentials showing a slow depolarisation during diastole were frequently recorded from the right atrium close to the crista terminalis. The atrial rate decreased, the maximal diastolic potential or resting potential and the size of the overshoot increased, and action potential durations were prolonged with age. Such alterations in the membrane potential related to age were not associated with changes in the atrial rate. The maximum rate of rise did not significantly differ in S-A nodes and right atria from rabbits of different ages. It may be concluded that the membrane permeability for K+ is increased and/or the permeability for Na+ is decreased during early postnatal period, resulting in alterations in the automaticity and parameters of the membrane potential. The relationship between maximum rate of rise and maximal diastolic potential or resting potential appears to be altered with age.
Echocardiographic Observations in Inflammatory Pericarditis
Authors: A. James Liedtke, Robert L. Dejoseph, Robert Zelis
Journal: Annals of Internal Medicine (1976)

Letters1 May 1976Echocardiographic Observations in Inflammatory PericarditisA. JAMES LIEDTKE, M.D., F.A.C.P., ROBERT L. DEJOSEPH, M.D., ROBERT ZELIS, M.D., F.A.C.P.A. JAMES LIEDTKE, M.D., F.A.C.P.Search for more papers by this author, ROBERT L. DEJOSEPH, M.D.Search for more papers by this author, ROBERT ZELIS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-5-573 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEchocardiography is a simple, noninvasive and reliable bedside technique, which has increasing clinical application in the diagnosis of pericardial effusion (1, 2). The present report describes an instance where this otherwise accurate method led to a falsely-positive diagnosis, presumably from acoustically silent fibrinous material, which appeared as a moderate-to-large pericardial effusion.An acutely ill, 30-year-old farmer was admitted to a local hospital with fever 40.3 °C [104.6 °F], productive cough, and physical findings of left lobar pneumonia complicated by an accompanying loud, two-component, pericardial friction rub without evidence for cardiac tamponade.Diplococcus pneumoniaewas noted on Gram stain of the...References1. FEIGENBAUM H: Echocardiographic diagnosis of pericardial effusion. Am J Cardiol 26:475-479, 1970 CrossrefMedlineGoogle Scholar2. POPPHARRISON RD: Echocardiography, in Noninvasive Cardiology, edited by WEISSLER AM. New York, Grune and Stratton, 1974, pp. 149-226 Google Scholar3. PATEGARDNERNORMAN JHR: Diagnosis of pericardial effusion by echocardiography. Ann Surg 165:826-829, 1967 CrossrefMedlineGoogle Scholar4. MCLEOD C: The pneumococci, in Bacterial and Myocotic Infections in Man, edited by DUBOS RJ. Philadelphia, J.B. Lippincott Company, 1958, pp. 230-247 Google Scholar5. FOWLER N: Disease of the pericardium, in The Heart, Arteries and Veins, edited by HURST JW, LOGUE RB. New York, McGraw-Hill Book Company, 1974, pp. 1387-1405 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Section of Cardiology Department of Medicine The Milton S. Hershey Medical Center College of Medicine The Pennsylvania State University Hershey, PA 17033 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySynthesis of Thioesters and ThiolactonesEchocardiographic diagnosis of pericardial disease 1 May 1976Volume 84, Issue 5Page: 573-574KeywordsEchocardiographyFeversPneumonia Issue Published: 1 May 1976 PDF downloadLoading ...
Gonadotropin-Releasing Hormone Deficiency in the Human (Idiopathic Hypogonadotropic Hypogonadism and Kallmann’s Syndrome): Pathophysiological and Genetic Considerations
Authors: Stephanie B. Seminara, Frances J. Hayes, William F. Crowley
Journal: Endocrine Reviews (1998)

I. Introduction II. Ontogeny of Normal GnRH Secretion A. Fetal life B. Neonatal and childhood periods C. Puberty D. Adulthood III. Historical Perspective IV. Clinical Presentation of GnRH Deficiency A. Congenital GnRH deficiency B. Adult-onset GnRH deficiency C. Variant or partial forms of GnRH deficiency D. Associated anomalies in KS E. Differential diagnosis V. Approaches to Studying GnRH Secretion A. Animal and in vitro studies B. Human studies VI. Patterns of GnRH Secretion in Men with GnRH Deficiency VII. Patterns of GnRH Secretion in Women with GnRH Deficiency VIII. Genetic Studies IX. X-Linked Genes Controlling GnRH Secretion A. Kallmann’s syndrome gene B. Adrenal hypoplasia congenita (AHC) gene product X. Autosomal Genes Controlling GnRH Secretion A. The genetics of autosomal inheritance B. GnRH gene C. GnRH receptor gene D. Other autosomal genes XI. Conclusion