tbuckley/cabot-search huggingface dataset:
Abstract 1165: PKC epsilon modulated miRNAs profiling during development of prostate cancer in transgenic adenocarcinoma of mouse prostate model
Authors: Bilal B. Hafeez, Weixiong Zhong, Ajit K. Verma
Journal: Cancer Research (2011)

Abstract MicroRNAs (miRNAs) are small nucleotides endogenously expressed non-coding RNAs that have been implicated in a wide range of cellular processes. Dysregulation of miRNA expression has been identified in a number of cancers including prostate. Evidence indicates that miRNAs are involved in prostate cancer (PCa) development and metastasis via activating several oncogenes and inhibiting tumor suppressor genes. However, the molecules’ targeting these microRNAs is poorly understood. Protein kinase C epsilon (PKC∈), a novel PKC isoforms, is over-expressed in both human and mouse PCa. We have previously shown that PKC∈ expression correlates with the aggressiveness of PCa. We generated PKC∈-deleted TRAMP mice by crossbreeding transgenic adenocarcinoma of mouse prostate (TRAMP) (TG//WT) mice with PKC∈ knock out (TG//KO) mice. Sixteen weeks old TG Wild-type (TG//WT), TG//PKC∈ Heterozygous (TG//Het) and TG//PKC∈ KO (TG//KO) mice were evaluated for PCa development and metastasis. We observed that deletion of PKC∈ in TRAMP mice inhibited PCa development and metastasis as observed by CT-PET scanning, tumor weight and histopathology of livers, lungs, kidneys and lymph nodes. To determine the clues about the miRNAs, which are modulated by PKC∈, we performed global miRNA profiling in prostate tissues of TG//WT and TG//KO mice by using miRNA Microarray chip containing transcripts of 750 miRNAs (Listed in Sanger miRBase Release 15.0). We observed a significant down-regulation of 7 miRNAs (miRNA762, miR125b-5p, miR-16, miR-467a-1, miR-574-3p, miRNA-451 and miR-669f) and up-regulation of 6 miRNAs (miR-1187, miR-1195, miR-2133, miR-574-5p, miR-690 and miR-709) in prostate tissues of TG//KO mice compared to TG//WT mice. It has been reported that miRNA-451 plays a role in the induction of mTOR signaling, which is well documented for its role in human PCa progression. Importantly, we observed 20-fold decreased expression of miRNA-451 in prostate tissues of TG//KO mice compared to TG//WT mice. It has been reported that up-regulation of miRNA-709 inhibits expression of BORIS, a tumor promoting transcription factor. We observed two fold induction of miRNA-709 in TG//KO mice. Taken together these finding suggest that PKC∈ plays an important role in PCa development and metastasis via up-regulating oncogenic miRNA and down regulating tumor suppressing miRNA. We suggest that these miRNAs modulated by PKC∈ have role in PCa development and metastasis. However further studies warranted to understand the functional implication of these miRNAs in human PCa. (Support: NIH Grant, CA35368). 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 1165. doi:10.1158/1538-7445.AM2011-1165
C16 laminin peptide increases angiotropic extravascular migration of human melanoma cells in a shell-less chick chorioallantoic membrane assay
Authors: C. Lugassy, H.K. Kleinman, S.E. Vernon, D.R. Welch, R.L. Barnhill
Journal: British Journal of Dermatology (2007)

As distinct from intravascular dissemination, extravascular migratory metastasis (EVMM) has been described as a potential additional mechanism of melanoma spread in which tumour cells migrate along the external surfaces of vessels. Recent experimental studies strongly suggest a correlation of angiotropism of melanoma cells with EVMM. Angiotropic melanoma cells are linked to the endothelium by an amorphous matrix confirmed to contain laminin.To investigate whether laminin plays a role in this extravascular mechanism of tumour spread.We tested the effect of the C16 laminin peptide on melanoma spread in a shell-less chick chorioallantoic membrane model.After 3 days, green fluorescent protein-expressing melanoma cells were observed spreading along or in the immediate proximity of vessels. The C16 laminin peptide significantly lengthened the distance of extravascular, angiotropic migration of melanoma cells. Histopathology confirmed the angiotropism of melanoma cells without intravasation, compatible with that observed with human angiotropic melanoma.The results of this study suggest that the C16 laminin gamma1 chain peptide has angiotropic, extravascular migration-promoting activity on human melanoma cells, and might be a molecular target for preventing melanoma metastasis.
Global Gene Expression Analysis Reveals Dynamic and Developmental Stage–Dependent Enrichment of Lead-Induced Neurological Gene Alterations
Authors: Samuel M. Peterson, Jun Zhang, Gregory Weber, Jennifer L. Freeman
Journal: Environmental Health Perspectives (2010)

BackgroundThe underlying genetic mechanisms specific to subtle neurological alterations associated with environmental lead (Pb) exposures have not been clearly elucidated.ObjectivesThe goal of this study was to identify novel gene targets and the underlying genetic mechanisms associated with developmental Pb neurotoxicity.MethodsWe first exposed zebrafish embryos to a range of Pb concentrations throughout early development to establish relative toxicity. Using the data from that experiment, we exposed another group of zebrafish embryos to a sublethal dose of Pb (100 ppb) immediately after fertilization through 72 or 120 hr postfertilization (hpf). Global gene expression was then analyzed for molecular pathways and gene ontology enrichment, and Western blot analysis was performed to investigate the translation of gene expression changes to protein levels.ResultsAfter 72 hpf, we identified 231 probes representing 90 nonredundant genes with well-established function or orthology to human genes as being altered by Pb exposure. This gene set was both confirmatory and novel in nature and was highly enriched for neurological development, function, and disease. Moreover, gene changes at this time point were correlated to altered protein levels. Alternatively, the gene set at 120 hpf did not share association with neurological development.ConclusionsGlobal gene expression alterations associated with developmental Pb exposure were dynamic and dependent on developmental stage. Gene expression alterations at the 72-hpf time point were highly enriched with genes and molecular pathways associated with neurological development and disease. Moreover, we identified a number of novel targets for future exploration into their role in the genetic mechanisms underlying Pb-induced neurological alterations.
Timing of simvastatin treatment: No matter the time of day, does UK policy reflect the evidence?
Authors: M. G Duerden
Journal: BMJ (2004)

EDITOR—Wallace et al highlight important issues on managing so called hyperlipidaemia.1 The timing of the statin dose is irrelevant, with current policy and practice not designed to deliver the clinical outcomes seen in recent drug trials.2 They studied suboptimal doses, which is common; data from the West Midlands show that 36% of patients are prescribed simvastatin 10 mg …
978. Reduced Immune Response to Adenovirus Vector Formulated with the Anti-Inflammatory Liposome DS/DOPE
Authors: Amber Price, Maria Limberis, James M. Wilson, Scott L. Diamond
Journal: Molecular Therapy (2006)

Introduction: Successful gene transfer to lung has been hindered by immune responses elicited against gene transfer vectors and transgenes as well as inefficient gene transfer to target cells. We have previously demonstrated that, when delivered intranasally, adenoviral (AdV) vectors formulated with the anti-inflammatory cationic lipid dexamethasone-spermine (DS) and the neutral lipid dioleoylphosphatidylethanolamine (DOPE) target transgene expression to airway epithelia and reduce cellular infiltration to the lung. Methods: C57Bl/6 mice were administered with two doses of AdV vector expressing either β-galactosidase (LacZ) or human α- antitrypsin (AAT), with or without DS/DOPE, at days 0 and 14 respectively. At various time points cytokine responses, T-cell responses and B-cell responses were quantified. Results: We found that the six hour acute response to AdV vector alone has higher serum levels of many inflammatory cytokines and chemokines, such as KC/GROα(6-fold increase), TNF-α(5.7-fold increase), and IL-6 (2.7-fold increase). Furthermore, the production of neutralizing antibody against AdV at day 28 was significantly reduced when at least one dose of vector was formulated with DS/ DOPE (AdV,AdV=400; AdV+DS/DOPE,AdV=60; AdV+DS/ DOPE,AdV+DS/DOPE= 213). ELISPOT assays on splenocytes, isolated from vector treated mice, on days 14, 28, and 34 suggest altered kinetics of T-cell response based on formulation of AdV with DS/DOPE, though not necessarily a reduced response to the LacZ transgene. However, the localized pulmonary response to the vectors following double administration was significantly reduced for AdV formulated with DS/DOPE compared to AdV alone as indicated by quantification of CD4 (204.7 + 107.3 vs. 478.8 + 258.9) and CD8 (305.3 + 175.3 vs. 571.8 + 238.4) immunohistochemistry. Conclusion: Taken together our results indicate that formulating AdV vector with DS/DOPE targets transgene expression to airway epithelia while reducing the immune response to AdV.
P25. Access to diagnostics: a bottleneck for immunotherapeutics development - case example of MAGE-A3 cancer immunotherapeutic
Authors: K Lykopoulos, P Collins, M Hall, R Ehness, J Barth, J Louahed
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Precision medicine with modern immunotherapeutics often requires pre-therapeutic access to novel and sometimes complex diagnostic tests. Test development and access to tests including reimbursement often lacks behind medicine development and availability of medicines, potentially
Improving Men's Health
Authors: Phil B. Fontanarosa, Helene M. Cole
Journal: JAMA (2006)

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
Withdrawal Treatment of Drug Addiction
Authors: Marie Nyswander
Journal: New England Journal of Medicine (1950)

THE withdrawal treatment for drug addiction presents a variety of problems requiring the application of medical, psychiatric and custodial knowledge. These problems have been most thoroughly studied at the United States Public Health Service Hospital in Lexington, Kentucky, which is devoted exclusively to drug addicts, and, indeed, the greater part of current knowledge of drug addiction, including etiology, treatment and physiologic mechanisms, has come from this hospital. Excellent descriptions of the withdrawal treatment used there have previously been published.1 , 2 However, there are many patients for whom hospitalization at Lexington is impractical or even impossible, and it is believed that such . . .
Effect of specific exercise strategy on need for surgery in patients with subacromial impingement syndrome: randomised controlled study
Authors: Theresa Holmgren, Hanna Björnsson Hallgren, Birgitta Öberg, Lars Adolfsson, Kajsa Johansson
Journal: British Journal of Sports Medicine (2014)

STUDY QUESTION Can a specific exercise strategy improve shoulder function and pain in patients with subacromial impingement syndrome, thereby decreasing the need for arthroscopic subacromial decompression? SUMMARY ANSWER Compared with a control exercise group, patients in the specific exercise group had significantly greater improvements in shoulder function and pain and fewer patients needed surgery at the three month assessment. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Different exercise programmes are used as first line treatment in patients with subacromial impingement syndrome, but conclusive evidence to support the efficacy for these programmes is lacking. This specific exercise strategy proved effective in improving shoulder function and pain in patients in whom earlier conservative treatment had failed.
Adrenomedullin reflects cardiac dysfunction, excessive blood volume, and inflammation in hemodialysis patients
Authors: Fumiki Yoshihara, Takeshi Horio, Satoko Nakamura, Masayoshi Yoshii, Chinami Ogata, Hajime Nakahama, Takashi Inenaga, Kenji Kangawa, Yuhei Kawano
Journal: Kidney International (2005)
Crohn's Disease — 50 Years Later
Authors: Henry D. Janowitz
Journal: New England Journal of Medicine (1981)

Only 50 years ago, Burrill Crohn, Leon Ginzburg, and Gordon Oppenheimer read their paper on regional ileitis.1 The evolution of our understanding of this fascinating and cruel disease is of such recent origin that the first two authors are, happily, still alive. One cannot escape the conviction that this really is a new disease, which emerged in the early part of this century, for it is difficult to believe that the great European pathologists of the 19th century who did such careful autopsies would have missed this striking pathologic entity or confused it with tuberculosis, whose appearance they knew so . . .
Vascular Responses in Diabetic Peripheral Neuropathy
Authors: J. A. Moorhouse, S. A. Carter, J. Doupe
Journal: BMJ (1966)

Lumbar Sympathectomy-Myers and Irvine BRmsH 883 the operation.It is believed that these cases are few in number and that the explanation for the response has yet to be provided. SummaryThe value of lumbar sympathectomy for intermittent claudication is disputed.Improvement would imply persistent release of collateral or vasomotor tone.It is doubtful whether afferent fibres are carried in the sympathetic trunk in sufficient number to be of significance.Thirty-one patients having 40 lumbar sympathectomies for intermittent claudication were studied before and 10 to 14 days after operation by strain-gauge plethysmography.Measurements were made of the resting flow, of the peak flow and time of its development during reactive hyperaemia, and of the distal arterial pressure in the calf muscle.No statistically significant increase could be demonstrated after sympathectomy in any of these parameters in the group as a whole.Nor could significant change be shown according to the clinical response to the operation, to the severity or duration of the symptoms, or to the site of the occlusion or extent of the disease.The flows both before and after sympathectomy were higher in the group showing clinical improvement, suggesting that spontaneous remission is more likely to occur when the disease is less severe.It is considered that there is no objective evidence of consistent haemodynamic benefit from lumbar sympathectomy for intermittent claudication.
Quantitative comparison of the effects of cholecystokinin, secretin, and pentagastrin on gastrointestinal myoelectric activity in the conscious fasted dog.
Authors: D L Wingate, E A Pearce, M Hutton, A Dand, H H Thompson, E Wunsch
Journal: Gut (1978)

The effects on gastrointestinal myoelectric activity of infused pentagastrin, cholecystokinin (CCK), and secretin at physiological doses were studied in live dogs with implanted serosal electrodes during 56 six-hour studies. Pentagastrin dose-dependently increased gastric and duodenal slow-wave frequencies; secretin and CCK did not. Pentagastrin and CCK diminished the incidence of fasting migrating myoelectric complexes (MMCs), but MMCs were abolished only in the proximal small intestine. Pentagastrin infusion was not reflected in an increased number of spikes, whereas CCK induced a dose-dependent increase in jejunal spike activity. Secretin dose-dependently decreased duodenal and jejunal spike incidence without a marked effect on MMC incidence. Analysis of patterns of spike activity showed significant dose-dependent changes with all three peptides. The different effects of pentagastrin and CCK on spike activity in these studies may have been a consequence of pentagastrin-stimulated gastric acid secretion. None of the three peptides produced a pattern of myoelectric activity which closely resembled that seen on feeding; since, unlike food, all three peptides had little or no effect on the distal small intestine, it seems unlikely that combinations of these peptides are responsible for the change induced by food. The failure of these peptides to abolish fasting patterns in the distal intestine suggests a possible mechanism for some types of post-vagotomy dysfunction.
Government will invest in research and innovation to stimulate UK economy
Authors: I. Torjesen
Journal: BMJ (2011)

The government will make more money available to small and medium sized businesses to help them research and develop innovative new products, especially in the science and technology sectors, in an attempt to promote economic growth.

As expected, the government’s Innovation and Research Strategy for Growth , published last week, confirms that its £4.6bn (€5.4bn; $7.2bn) research programme investment will be ringfenced. An extra £495m will be made available for capital projects, special support for life sciences, and electronic infrastructure investment.

The strategy gives a name to the planned £200m network of technology and innovation centres: Catapult centres. These will act as a bridge between academia and business to support the commercialisation of new …
Health Services in Israel
Authors: Bruce Balfe
Journal: JAMA (1969)

<i>Health Services in Israel</i>, a comprehensive profile of the Israeli health system as it existed in 1965, is the third in a series of reference volumes which began in 1952. This series indicates the unusual nature of the problems with which the people of Israel have had to deal, and the amazing success which they achieved in the years since Israel became a state. In 1948, the Israeli Parliament gave every Jew the right to immigrate to Israel. Since that time, the Jewish population has more than trebled, an immigration rate which, "... in proportion to the settled population, would normally be considered impossible. The right to immigrate was virtually unlimited by any kind of qualification, including physical condition.... Communicable diseases such as tuberculosis, filariasis, and trachoma were rife among them, infant mortality was high, and hygiene was low." This was the point from which the Israel health system began. In
UK GPs will produce blueprint for the future
Authors: L. Beecham
Journal: BMJ (1999)

General practitioners in the United Kingdom, other healthcare workers, patients, policymakers, and politicians will be asked to contribute ideas over the next few months to a consultation document on the strengths of general practice, the threats, and the solutions for the next decade.

Announcing this at the conference of local medical committees last week, John Chisholm, chairman of the General Practitioners Committee, said that it was time for GPs to define their own agenda for the future: “We need to take stock of what being a GP should mean in the next millennium, what …
Less Na/H-exchanger to treat heart failure: a simple solution for a complex problem?
Authors: M STAGG, C TERRACCIANO
Journal: Cardiovascular Research (2004)

See article by Baartscheer et al.  [1]  (pages 83–92) in this issue .

Heart failure is one of the major causes of mortality and morbidity in the western world. Enormous investments have been made for researching the treatment of this disease with the aim of reconstructing the chain of events at the organ, cellular, and molecular levels that leads to cardiac hypertrophy and/or heart failure. This challenge is extremely complex because almost every cellular and molecular system is affected in heart failure. These modifications can be a cause or a consequence of heart failure, can be compensatory or detrimental, or can be simply epiphenomena.

The ideal target for heart failure research is the identification of key factors that are commonly activated by the underlying diseases and are responsible for inducing the functional changes. Normalisation of these key factors would restore cardiac function or, at the very least, prevent further dysfunction. There is now evidence that one of these key factors is the Na+/H+-exchanger (NHE-1).

Several studies have now shown that inhibiting the NHE-1 in heart failure is beneficial. In the present issue of Cardiovascular Research the article by Baartscheer et al. [1] presents further evidence for this effect.

Investigations into the role of the NHE-1 in cardiac disease have been examined under two main clinical scenarios: (1) in the setting of ischaemia/reperfusion; (2) during progression from hypertrophy to heart failure. … 

*Corresponding author. Tel.: +44 1895 453 874; fax: +44 1895 828 900. Email address: c.terracciano{at}imperial.ac.uk
2-Arachidonoylglycerol Signaling in Forebrain Regulates Systemic Energy Metabolism
Authors: Kwang-Mook Jung, Jason R. Clapper, Jin Fu, Giuseppe D'Agostino, Ana Guijarro, Dean Thongkham, Agnesa Avanesian, Giuseppe Astarita, Nicholas V. DiPatrizio, Andrea Frontini, Saverio Cinti, Sabrina Diano, Daniele Piomelli
Journal: Cell Metabolism (2012)