tbuckley/cabot-search huggingface dataset:
Cks1 Regulates cdk1 Expression: A Novel Role during Mitotic Entry in Breast Cancer Cells
Authors: Louise Westbrook, Marina Manuvakhova, Francis G. Kern, Norman R. Estes, Harish N. Ramanathan, Jaideep V. Thottassery
Journal: Cancer Research (2007)

Abstract Cks1, a small protein whose expression is strongly associated with aggressive breast tumors, is a component of cyclin-cdk complexes, as well as the SCFSkp2 ubiquitin ligase. In these studies, we explored its roles in estrogen receptor–positive breast tumor cells. When exposed to the antiestrogen ICI 182780, these cells accumulate in G1 by reducing the expression of Cks1, and increasing the levels of p130/Rb2, a cdk2 inhibitor and SCFSkp2 target. Heregulin β1 or estradiol abrogate antiestrogen effects by increasing Cks1 expression, down-regulating p130/Rb2 and inducing S phase entry. Depletion of Cks1 in these cells by RNA interference concomitantly decreased Skp2 and up-regulated p130/Rb2 and another SCFSkp2 target, p27Kip1. Remarkably, however, Cks1-depleted cells not only exhibit slowed G1 progression, but also accumulate in G2-M due to blocked mitotic entry. Notably, we show that cdk1 expression, which is crucial for M phase entry, is drastically diminished by Cks1 depletion, and that restoration of cdk1 reduces G2-M accumulation in Cks1-depleted cells. cdk1 reduction in Cks1-depleted cells is a consequence of a marked decrease in its mRNA and not due to alteration in its proteolytic turnover. Both heregulin β1 and estradiol could neither restore cdk1 nor sustain cycling in Cks1-depleted cells, although classical estrogen receptor function remained unaltered. Cks1 depletion also decreased Skp2 in human mammary epithelial cells without altering cell cycle progression. Thus, the indispensability of Cks1 to the breast cancer cell cycle, versus its redundancy in normal cells, suggests that Cks1 abrogation could be an effective interventional strategy in breast cancer. [Cancer Res 2007;67(23):11393–401]
Poliolike Cases Probed in California
Authors: Bridget M. Kuehn
Journal: JAMA (2014)

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
Therapeutic targets in age-related macular disease
Authors: Alan C. Bird
Journal: Journal of Clinical Investigation (2010)

Age-related macular disease (AMD) accounts for more than 50% of blind registration in Western society. Patients with AMD are classified as having early disease, in which visual function is well preserved, or late disease, in which central vision is lost. Until recently, there was no therapy available by which the course of the disorder could be modified. Now, the most common form of late-stage AMD - choroidal neovascularization - responds to treatment with anti-VEGF therapies; although visual loss is modified in a portion of these cases, no therapeutic approach exists that alters the evolution from early to late disease. However, as discussed in this Review, research over the last few years has demonstrated several features of AMD that are likely to be amenable to treatment. Potential targets for treatment are described, and possible therapeutic approaches are discussed.
How US healthcare cuts could kill me
Authors: Lori Smith
Journal: BMJ (2005)

I am a citizen of the United States, and I am suffering and may die because of human rights violations in my country. I work with the Poor People's Economic Human Rights Campaign (www.economichumanrights.org) and help represent the millions of people in my country who otherwise would have no voice. I sit on the board of directors of the Tennessee Health Care Campaign and I am president of Music for Health Care. These organisations believe that health care is a human right, and we work closely with local and national organisations in the pursuit of health care for all.

My home state of Tennessee is the model for a national political campaign to dismantle vital social programmes for sick and poor people throughout the US. And whatever the model is for the US unfortunately becomes the model for the world.

> These are the largest cuts in US history, and deaths have already occurred as a result

There has been a tendency to believe that poverty, hunger, homelessness, and lack of health care are nearly non-existent in the US. After all, the US is …
819 HEALTH-RELATED QUALITY OF LIFE (HRQOL) WITH ALBINTERFERON ALFA-2B PLUS RIBAVIRIN IN IFN TREATMENT-NAIVE PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C
Authors: S. Pianko, E. Yoshida, S. Zeuzem, Y. Benhamou, V. Bain, E. Pulkstenis, J.G. McHutchison, G.M. Subramanian
Journal: Journal of Hepatology (2008)
Advance Directives, Due Process, and Medical Futility
Authors: Robert L. Fine, Thomas Wm. Mayo
Journal: Annals of Internal Medicine (2004)

Letters2 March 2004Advance Directives, Due Process, and Medical FutilityRobert L. Fine, MD and Thomas Wm. Mayo, JDRobert L. Fine, MDFrom Baylor Health Care System, Dallas, TX 75204, and Southern Methodist University/Dedman School of Law, Dallas, TX 75275.Search for more papers by this author and Thomas Wm. Mayo, JDFrom Baylor Health Care System, Dallas, TX 75204, and Southern Methodist University/Dedman School of Law, Dallas, TX 75275.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-5-200403020-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Berger suggests that the term futility “defies meaningful or clinically useful definition” and suggests that medically appropriate is the better term. Finucane, on the other hand, acknowledges that futility may have qualitative and/or physiologic components, but he goes on to suggest that futility is a “smokescreen.” Our experience suggests that although some find futility difficult to define, most physicians now know it when they see it (to paraphrase the late Justice Potter Stewart). We find the term useful not as a smokescreen, but as a quick reference to a class of patients who cannot recover or get well, ... Author, Article, and Disclosure InformationAuthors: Robert L. Fine, MD; Thomas Wm. Mayo, JDAffiliations: From Baylor Health Care System, Dallas, TX 75204, and Southern Methodist University/Dedman School of Law, Dallas, TX 75275. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoResolution of Futility by Due Process: Early Experience with the Texas Advance Directives Act Robert L. Fine and Thomas Wm. Mayo Advance Directives, Due Process, and Medical Futility Jeffrey T. Berger Advance Directives, Due Process, and Medical Futility Thomas E. Finucane Advance Directives, Due Process, and Medical Futility Anne L. Flamm and Martin L. Smith Metrics 2 March 2004Volume 140, Issue 5Page: 404KeywordsFearImmunityMedical ethicsMedical lawMotivation ePublished: 2 March 2004 Issue Published: 2 March 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
1042 EFFICACY AND SAFETY RESULTS OF ALBINTERFERON ALFA-2B IN COMBINATION WITH RIBAVIRIN IN INTERFERON-ALFA TREATMENT NAIVE PATIENTS WITH GENOTYPE 2 OR 3 CHRONIC HEPATITIS C
Authors: D. Nelson, Y. Benhamou, W.L. Chuang, E. Lawitz, R. Flisiak, M. Rodriguez-Torres, V. Bain, K. Patel, P.W. Cronin, E. Pulkstenis, G.M. Subramanian, J.G. McHutchison
Journal: Journal of Hepatology (2009)
SYNTHESIS OF ALL PLASMA PROTEIN FRACTIONS EXCEPT GAMMA GLOBULINS BY THE LIVER
Authors: Leon L. Miller, William F. Bale
Journal: The Journal of Experimental Medicine (1954)

Lysine-epsilon-C(14)-labeled plasma proteins produced by the normal rat and the isolated perfused rat liver have been fractionated by preparative zone electrophoresis. The isolated perfused liver incorporates lysine-epsilon-C(14) into the plasma albumin, alpha globulin, and beta globulin (including fibrinogen) fractions. No significant C(14) incorporation into the trichloracetic acid-precipitable proteins of the gamma globulin fraction was observed. Presumptive evidence indicates that the alpha globulins turn over more rapidly than any other major plasma protein fraction. The increased production of gamma globulins in liver disease is discussed.
536. Adenoviral Vector-Mediated Gene Therapy for Adenocortical Carcinoma: Therapeutic Strategies and Safety Considerations
Authors: Luisa Barzon, Urska Trost, Monia Pacenti, Anna-Lisa Stefani, Marta Trevisan, Giulia Masi, Karina Fincati, Giorgio Palù
Journal: Molecular Therapy (2005)

Top of pageAbstract
Recombinant adenoviruses are widely used in gene therapy clinical trials. Since these vectors have a marked tropism for the adrenal gland, they could be suitable for gene therapy of adrenocortical carcinoma (ACC). However, adrenal tropism has safety implications, highlighted by the fact that adenoviral infection of adrenal cells can impair steroidogenesis. Aim of this study was the construction of E1/E3 deleted adenoviral vectors carrying different combinations of therapeutic genes and evaluation of their efficacy against ACC and their effect on adrenal gene expression profile. Recombinant adenoviral vectors were generated by cloning therapeutic genes (HSV-TK and mutant HSV-TK30, mouse GM-CSF, mouse IL-12) and reporter genes (LacZ, eGFP) into shuttle vectors followed by homologous recombination with adenoviral genome in bacteria. Viral stocks were prepared by transfection and expansion in 293 cells. Human ACC cell lines NCI-H295R and SW13 were demonstrated to be efficiently trasduced by adenoviral vectors at MOI 10 and 100 and to express high levels of the coxsackie and adenovirus receptor CAR. Cytotoxicity assay showed that ACC cells transduced with vectors carrying mutant HSV-TK30 had higher sensitivity to ganciclovir than cells infected with adenoviral vectors carrying wild-type HSV-TK, either in a monocistronic sequence or in a polycistronic combination. In vivo experiments in nude mice s.c. inoculated with ACC cells demonstrated significant inhibition of tumor growth by intratumor injection with vectors carrying cytokine genes and a complete regression of tumor masses injected with adenoviral vectors carrying combinations of suicide and cytokine genes after ganciclovir treatment. DNA microarray analysis of gene expression profile of ACC cells infected with reporter adenoviral vectors showed overexpression of genes involved in cortisol synthesis, including CYP21, and of the |[szlig]|-adrenergic receptor ADRA1B, and down-regulation of CYP11B2, ACE, and the adenovirus E1A-binding protein gene BS69. In conclusion, adenoviral vectors efficiently transduce ACC cells in vitro and in vivo. Combined adenoviral vector-mediated delivery of suicide and cytokine genes eradicates tumors in mice. Adenoviral vector infection of ACC cells modulates gene expression profile, upregulating genes involved in cortisol production and stress response.
Modulated gap junctional intercellular communication as a biomarker of PAH epigenetic toxicity: structure-function relationship.
Authors: B L Upham, L M Weis, J E Trosko
Journal: Environmental Health Perspectives (1998)

Cancer is a multistage multimechanism process involving gene and/or chromosomal mutations (genotoxic events), altered gene expression at the transcriptional, translational, and post-translational levels (epigenetic events), and altered cell survival (proliferation and apoptosis or necrosis), resulting in an imbalance of the organism's homeostasis. Maintenance of the organism's homeostasis depends on the intricate coordination of genetic and metabolic events between cells via extracellular and intercellular communication mechanisms. The release of a quiescent cell, whether normal or premalignant, from the suppressing effects of communicating neighbors requires the downregulation of intercellular communication via gap junctions, thereby allowing factors that control intracellular events to exceed a critical mass necessary for the cell to either proliferate or undergo apoptosis. Therefore, determining the role an environmental pollutant must play in the multistage carcinogenic process includes mechanisms of epigenetic toxicity such as the effects of a compound on gap junctional intercellular communication (GJIC). A classic example of a class of compounds in which determination of carcinogenicity focused on genotoxic events and ignored epigenetic events is polycyclic aromatic hydrocarbons (PAHs). The study of structure-activity relationships of PAHs has focused exclusively on the genotoxic and tumor-initiating properties of the compound. We report on the structure-activity relationships of two- to four-ringed PAHs on GJIC in a rat liver epithelial cell line. PAHs containing a bay or baylike region were more potent inhibitors of GJIC than the linear PAHs that do not contain these regions. These are some of the first studies of determine the epigenetic toxicity of PAHs at the epigenetic level.
Medical arrangements for the European Youth Swimming and Diving Championships--1973
Authors: Stanley Sheffrin
Journal: British Journal of Sports Medicine (1973)

The Fourth European Youth Swimming and Diving Championships were to be held at Leeds from August 8th -11th, 1973.It was expected that 24 countries would be sending teams and that there would be about 400 competitors, all 15 years of age or under, together with coaches and officials.This was considered to be the largest event of its type ever staged in this country.
Vitamin K regimens and incidence of childhood cancer in Denmark
Authors: J H Olsen, H Hertz, K Blinkenberg, H Verder
Journal: BMJ (1994)

Number ofwomen who were breastfeeding and the number andproportion ofbreastfed infants who received vitamin K No of No (%/6) of women infants breast who feeding received (n-207) vitamin K At discharge 162 161 (99) At 7 days 162 143 (88) At 6 weeks 145 57 (39)
Abstract 3412: Hypoxia induces EMT in primary melanoma and MET in metastatic melanoma
Authors: Chieh-Fang Cheng, Amato J. Giaccia, Marianne B. Powell
Journal: Cancer Research (2011)

Abstract A low oxygen microenvironment (hypoxia) is observed in the skin and in solid tumors. In several different types of cancers hypoxia has been shown to induce primary tumor cell migration and cancer metastasis. Epithelial to mesenchymal transition (EMT) is an important process involving the transition of primary tumor cells to mobile metastatic tumor cells. Hypoxia has been reported to induce EMT in breast and ovarian cancers. However, little is known about the settlement process after metastatic tumor cells reach the distant metastatic site. In this study, we compared the effect of hypoxia on several primary and metastatic melanoma cell lines in cell morphology and cell motility. We observed different expression patterns of cell surface markers and transcription factors regulated by hypoxia that are important for the EMT process between primary and metastatic tumor cells. While hypoxia induces the expression of EMT markers in primary melanoma, it represses the expression of these markers as well as cell migration in metastatic melanomas. Furthermore, cell migration induced by hypoxia in primary melanoma cell is blocked by either HIF1α or HIF2α knock down. Cell migration repressed by hypoxia is reversed by knocking down HIF1α but not HIF2α in metastatic tumor cells. We propose that depending on the state of tumor progression, hypoxia can induce EMT in primary melanomas and MET in metastatic melanomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3412. doi:10.1158/1538-7445.AM2011-3412
Fed up with forms
Authors: M. McCartney
Journal: BMJ (2014)

Where’s the joy in medicine? Junior doctors are the scaffolding that supports the great weight of the NHS. We who use and work in the NHS should cherish them through their stress and sleep deprivation. But thanks to the medical leadership of the past decade, junior doctorhood has been emptied of professional pride and filled with multiple bits of paper to check “competencies.” The feedback forms, 360° appraisals, team assessments of behaviour, and end of placement reports are the tick box nonsense to which we now subject them.⇑

For me, several years removed from training, the stony bureaucracy and burdensome administration are astonishing. Modern shift patterns have broken teams where peer …
Inhibition of Parathyroid Hormone Secretion by 25-Hydroxycholecalciferol and 24,25-Dihydroxycholecalciferol in the Dog
Authors: Janet M. Canterbury, Sam Lerman, Alice J. Claflin, Helen Henry, Anthony Norman, Eric Reiss
Journal: Journal of Clinical Investigation (1978)

We studied the effects of vitamin D metabolites on parathyroid hormone (PTH) secretion. Test materials were injected into the cranial thyroid artery of the dog, and immunoreactive PTH was measured frequently in serum samples from the inferior thyroid vein and the femoral vein. This model for the study of secretion had previously been validated with the use of known modulators on PTH secretion. In control experiments, injection of 100% ethanol, the vehicle in which cholecalciferol (D3) metabolites were suspended, resulted in no change in PTH secretion. Likewise, native vitamin D3, in doses ranging from 250 to 1,250 ng had no effect on PTH secretion. 25-Hydroxycholecalciferol, 25-(OH)D3, in doses of 125-240 ng, caused complete suppression of PTH secretion. When 24,25-dihydroxycholecalciferol, 24,25-(OH)2D3, was injected in doses of 50-250 ng, suppression of PTH secretion was again complete; in doses of 5 ng, injection of this metabolite resulted in significant but incomplete suppression of secretion. In doses of 50-250 ng, 1,25-(OH)2D3 strongly stimulated PTH secretion, but in a dose of 5 ng this metabolite had no effects. Injection of equal doses of 1,25-(OH)2D3 and 24,25-(OH)2D3 resulted in significant suppression of PTH secretion. Hypocalcemia-induced stimulation of PTH secretion was suppressed by 24,25-(OH)2D3 while hypercalcemia-induced suppression of PTH secretion was stimulated by 1,25-(OH)2D3. In all experiments showing suppression of PTH secretion, peripheral PTH decreased. Arguments are presented for considering the suppressive effects of D3 metabolites as physiologic modulators. However, this stimulating effect of 1,25-(OH)2D3 occurred only in pharmacologic doses and hence probably has no physiologic relevance.
Inequalities in access to healthcare of hepatitis C patients in a general population
Authors: Cyril Hatem, Anne Minello, Anne Claire Gossard, Valerie Jooste, Philippe Evrard, Benedicte Obert, Emmanuel Rassiat, Chantal Milan, Elisabeth Monnet, Jean Philippe Miguet, Solange Bresson Hadni, Patrick Hillon
Journal: Journal of Hepatology (2002)
Transcription of human herpesvirus-like agent (HHV-8) in Kaposi's sarcoma.
Authors: Y Q Huang, J J Li, W G Zhang, D Feiner, A E Friedman-Kien
Journal: Journal of Clinical Investigation (1996)

Recently, DNA sequences of what appear to be a unique human herpesvirus-like agent (HHV-8) have been detected in different types of Kaposi's sarcoma (KS) tumors (Chang, Y., E.C. Cesarman, M.S. Pessin, F. Lee, J.C. Culpepper, D.M. Knowles, and P.S. Moore. 1994. Science (Wash. DC). 266:1865-1869). To further elucidate the possibility that HHV-8 plays a role in the pathogenesis of KS, the expression of HHV-8 RNA was examined in fresh KS tissue specimens which were found to harbor HHV-8 DNA by polymerase chain reaction (PCR). The transcription of HHV-8 RNA was detected by RT-PCR in 26 of 29 specimens (89.7%) of the KS tumors including 2 of 3 CKS and 24 of 26 AIDS-KS. No positive signal was detected in eight biopsy specimens of normal skin from healthy donors. By Northern blot analysis, the expression of HHV-8 was detected in 2 of 10 KS tumors examined. Furthermore, the RNA transcripts were observed in endothelial cells lining the irregular vascular spaces and perivascular spindle-shaped cells histologically characteristic of KS in 2 out of 8 different KS specimens examined by in situ hybridization using an antisense probe specific of HHV-8. The detection of RNA expression of HHV-8 in KS tumors further supports the possible etiopathogenic role of this virus in the development of KS.
Modeling Chronic Glycemic Exposure Variables as Correlates and Predictors of Microvascular Complications of Diabetes
Authors: Trevor J. Orchard, Tina Costacou, Rachel G. Miller, Catherine T. Prince, Georgia Pambianco
Journal: Diabetes Care (2007)

We read with interest the article by Dyck et al. (1), in which the authors described a chronic glycemic exposure variable (GEi) in the Rochester Study. They examined GEi and its individual components (A1C, duration, and age at onset) in terms of prediction/correlation with complications and concluded that GEi is generally predicted better than its individual components (see Table 3 of ref. 1).

Dyck et al. compared their results with our previously published analyses (2) using a different chronic glycemic exposure variable, A1 months, noting …
Stroke Decline: Implications and Prospects
Authors: Robert I. Levy
Journal: New England Journal of Medicine (1979)

Good news is worth telling and retelling. Age-adjusted cardiovascular mortality rates have declined almost 32 per cent over the last 30 years. In the last 10 years, however, the decrease has accelerated precipitously, accounting for over two thirds of the total 30-year reduction, and is seen in both sexes, in whites and nonwhites and in every age-decade band from the second to beyond the eighth. Not only have death rates declined, but despite an aging and ever increasing population, the total number of cardiovascular deaths fell below one million in 1975 for the first time in almost a decade and . . .
Victims of Memory: Incest Accusations and Shattered Lives
Authors: Burton C. Einspruch
Journal: JAMA (1996)

Incest is one of the most horrendous forms of sexual abuse and lends itself to the creation of a body of both serious and sensationalistic literature. Accusations of imagined transgressions and their legal consequences have the potential of creating victims. At this time Philadelphia's False Memory Syndrome Foundation states that at least 800 civil and criminal cases have been filed based on repressed memories. Although long debated, judges in four cases have ruled that "testimony based on so-called repressed memories cannot be admitted because scientists say there is no evidence that such recollections are reliable" (<i>National Law Journal</i>, Monday, June 12, 1995, p A7). In the foreword to his book<i>Victims of Memory</i>, Paul Pendergrast, not just as a parent but also as a professional investigative journalist and scholar, has probed the question of "how perfectly normal people like me could come to believe in such horrible delusions, and how