tbuckley/cabot-search huggingface dataset:
The Pharmacology of l-DOPA-Induced Dyskinesia in Parkinson’s Disease
Authors: Philippe Huot, Tom H. Johnston, James B. Koprich, Susan H. Fox, Jonathan M. Brotchie
Journal: Pharmacological Reviews (2013)

l-3,4-Dihydroxyphenylalanine (l-DOPA) remains the most effective symptomatic treatment of Parkinson's disease (PD). However, long-term administration of l-DOPA is marred by the emergence of abnormal involuntary movements, i.e., l-DOPA-induced dyskinesia (LID). Years of intensive research have yielded significant progress in the quest to elucidate the mechanisms leading to the development and expression of dyskinesia and maintenance of the dyskinetic state, but the search for a complete understanding is still ongoing. Herein, we summarize the current knowledge of the pharmacology of LID in PD. Specifically, we review evidence gathered from postmortem and pharmacological studies, both preclinical and clinical, and discuss the involvement of dopaminergic and nondopaminergic systems, including glutamatergic, opioid, serotonergic, γ-aminobutyric acid (GABA)-ergic, adenosine, cannabinoid, adrenergic, histaminergic, and cholinergic systems. Moreover, we discuss changes occurring in transcription factors, intracellular signaling, and gene expression in the dyskinetic phenotype. Inasmuch as a multitude of neurotransmitters and receptors play a role in the etiology of dyskinesia, we propose that to optimally alleviate this motor complication, it may be necessary to develop combined treatment approaches that will target simultaneously more than one neurotransmitter system. This could be achieved via three ways as follows: 1) by developing compounds that will interact simultaneously to a multitude of receptors with the required agonist/antagonist effect at each target, 2) by targeting intracellular signaling cascades where the signals mediated by multiple receptors converge, and/or 3) to regulate gene expression in a manner that has effects on signaling by multiple pathways
Fibrocalcific Aortic Valve Disease
Authors: Robert M. Weiss, Jordan D. Miller, Donald D. Heistad
Journal: Circulation Research (2013)

Studies in vitro and in vivo continue to identify complex-regulated mechanisms leading to overt fibrocalcific aortic valve disease (FCAVD). Assessment of the functional impact of those processes requires careful studies of models of FCAVD in vivo. Although the genetic basis for FCAVD is unknown for most patients with FCAVD, several disease-associated genes have been identified in humans and mice. Some gene products which regulate valve development in utero also protect against fibrocalcific disease during postnatal aging. Valve calcification can occur via processes that resemble bone formation. But valve calcification can also occur by nonosteogenic mechanisms, such as formation of calcific apoptotic nodules. Anticalcific interventions might preferentially target either osteogenic or nonosteogenic calcification. Although FCAVD and atherosclerosis share several risk factors and mechanisms, there are fundamental differences between arteries and the aortic valve, with respect to disease mechanisms and responses to therapeutic interventions. Both innate and acquired immunity are likely to contribute to FCAVD. Angiogenesis is a feature of inflammation, but may also contribute independently to progression of FCAVD, possibly by actions of pericytes that are associated with new blood vessels. Several therapeutic interventions seem to be effective in attenuating the development of FCAVD in mice. Therapies which are effective early in the course of FCAVD, however, are not necessarily effective in established disease.
Building a healthier Scotland
Authors: Bryan Christie
Journal: BMJ (2005)

The Scottish National Party wants to see adults and children swapping the crisp and couch for fruit, fibre, and physical jerks. Bryan Christie reports

Annual health checks for all school pupils, free fruit for pregnant women, and the developmentof rural hospitals are promised in the Scottish National Party's election manifesto to help make Scotland a healthier country. The party's health proposals are based around giving greater priority to the prevention of ill health while reshaping the NHS to improve local access and accountability.

Providing services over large and sparsely populated geographical areas has always been a challenge in Scotland. At the moment there are …
Gene transfer and vascular disease
Authors: E. G Nabel, V. J Pompili, G. E Plautz, G. J Nabel
Journal: Cardiovascular Research (1994)

Journal Article Gene transfer and vascular disease Get access Elizabeth G Nabel, Elizabeth G Nabel University of Michigan Medical Center, Ann Arbor, MI 48109-0688, USA - Department of Internal Medicine: E G Nabel, V J Pompili, G J Nabel; Department of Pediatrics: G E Plautz. Correspondence to Dr E G Nabel. Search for other works by this author on: Oxford Academic PubMed Google Scholar Vincent J Pompili, Vincent J Pompili University of Michigan Medical Center, Ann Arbor, MI 48109-0688, USA - Department of Internal Medicine: E G Nabel, V J Pompili, G J Nabel; Department of Pediatrics: G E Plautz. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gregory E Plautz, Gregory E Plautz University of Michigan Medical Center, Ann Arbor, MI 48109-0688, USA - Department of Internal Medicine: E G Nabel, V J Pompili, G J Nabel; Department of Pediatrics: G E Plautz. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gary J Nabel Gary J Nabel University of Michigan Medical Center, Ann Arbor, MI 48109-0688, USA - Department of Internal Medicine: E G Nabel, V J Pompili, G J Nabel; Department of Pediatrics: G E Plautz. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 4, April 1994, Pages 445–455, https://doi.org/10.1093/cvr/28.4.445 Published: 01 April 1994 Article history Received: 25 September 1992 Accepted: 08 November 1993 Published: 01 April 1994
α <sub>M</sub> β <sub>2</sub> Integrin Activation Prevents Alternative Activation of Human and Murine Macrophages and Impedes Foam Cell Formation
Authors: Valentin P. Yakubenko, Ashish Bhattacharjee, Elzbieta Pluskota, Martha K. Cathcart
Journal: Circulation Research (2011)

Rationale: The alternative activation of monocytes by interleukin (IL)-13 and IL-4 is a significant component of the inflammatory response. The consequences of alternative activation in inflammatory diseases remain to be determined. Objective: In this report, we explored how integrins, receptors important for monocyte migration to inflammatory sites, regulate IL-13–mediated monocyte activation. We focused on the analysis of 2 proteins, which are upregulated during the alternative activation and are important for the development of atherosclerosis, an oxidative enzyme 15-lipoxygenase (15-LO) and a scavenger receptor CD36. Methods and Results: We found that adhesion of resting monocytes through β 2 integrins and inside-out activation of β 2 integrins by monocyte chemoattractant protein-1 did not change IL-13–stimulated 15-LO upregulation; however, preincubation of monocytes with the antibody MEM48, which generates full activation of β 2 integrins, significantly inhibited 15-LO mRNA and protein expression. In contrast, activation of β 1 integrins had no effect on 15-LO expression. Analysis of integrin clustering through α M , α L , α X , and α D subunits demonstrated the pivotal role for integrin α M β 2 in inhibiting 15-LO expression. IL-13 treatment upregulates 15-LO–dependent CD36 expression on human monocytes; our studies showed that β 2 integrin activation and α M integrin clustering significantly inhibited IL-13–dependent CD36 mRNA and protein expression, as well as CD36-related foam cell formation. Moreover, IL-13 stimulation of α M -deficient peritoneal macrophages demonstrated an upregulated level of 15-LO induction, CD36 expression, and lipid accumulation as compared with wild-type controls. Conclusions: The adhesion of monocytes/macrophages through activated integrin α M β 2 has a regulatory and potential atheroprotective function during the alternative activation of macrophages.
INACTIVATION OF ENDOTOXIN BY A HUMORAL COMPONENT
Authors: Maurice Landy, Robert-John Trapani, Murray J. Shear
Journal: The Journal of Experimental Medicine (1959)

The immunological properties of typhoid endotoxin were investigated after incubating it with serum under conditions in which EDC (endotoxin-detoxifying component) was operative. Brief interaction of endotoxin in vitro with this system in serum (human, rabbit, mouse) abolished its antigenicity for rabbits. Suitable modification of the host permitted separate elicitation of toxic and antigenic responses to typhoid endotoxin. Endotoxin altered by EDC was still capable of precipitating specific antibody; moreover, it did so in a manner which resembled that of the haptenic polysaccharide.
Hypoxia is an inducer of vasodilator agents in peritoneal macrophages of cirrhotic patients
Authors: Pilar Cejudo-Martín, Manuel Morales-Ruiz, Josefa Ros, Miguel Navasa, Guillermo Fernández-Varo, Josep Fuster, Francisca Rivera, Vicente Arroyo, Juan Rodés, Wladimiro Jiménez
Journal: Hepatology (2002)

The aim of the investigation was to assess whether hypoxia induces the production of endogenous vasoactive peptides in macrophages of cirrhotic patients with ascites because low tissue oxygenation is a relatively frequent event in these patients. Peritoneal macrophages were isolated from ascites, seeded on well plates, and cultured at different times under hypoxic (5% O 2 ) or normoxic conditions (21% O 2 ). Then, accumulation of vasoactive peptides sensitive to hypoxia including endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and adrenomedullin (ADM) was measured. Only VEGF and ADM were constitutively secreted, and hypoxia further stimulated the release of these vasodilator peptides. In concordance, increased messenger RNA (mRNA) levels of VEGF and ADM were found at culturing macrophages in hypoxia. This characteristic response was not observed in circulating monocytes of either cirrhotic patients or healthy subjects. Next the expression of the transcription factor, hypoxia inducible factor 1 (HIF-1), was analyzed. Expression of HIF-1α and HIF-1β messengers and HIF-1β protein subunit remained unchanged regardless of O 2 tension, whereas HIF-1α protein subunit was overexpressed under hypoxic conditions. Moreover, conditioned medium from macrophages cultured under hypoxic conditions promoted a larger nitric oxide (NO) release in endothelial cells than that of normoxic macrophages. In conclusion, these data indicate that hypoxia induces the synthesis of VEGF and ADM in macrophages of cirrhotic patients, likely through HIF-1-enhanced transcriptional activity. These data suggest that a local reduction in O 2 tension could enhance the synthesis of macrophage-derived vasodilators, thus aggravating the circulatory disturbance of these patients.
THE TREATMENT OF ALCOHOLISM BY SUGGESTION.
Authors: F. A. BURRAL
Journal: JAMA (1997)

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
EMD 1214063 and EMD 1204831 Constitute a New Class of Potent and Highly Selective c-Met Inhibitors
Authors: Friedhelm Bladt, Bettina Faden, Manja Friese-Hamim, Christine Knuehl, Claudia Wilm, Claus Fittschen, Ulrich Grädler, Michael Meyring, Dieter Dorsch, Frank Jaehrling, Ulrich Pehl, Frank Stieber, Oliver Schadt, Andree Blaukat
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The mesenchymal–epithelial transition factor (c-Met) receptor, also known as hepatocyte growth factor receptor (HGFR), controls morphogenesis, a process that is physiologically required for embryonic development and tissue repair. Aberrant c-Met activation is associated with a variety of human malignancies including cancers of the lung, kidney, stomach, liver, and brain. In this study, we investigated the properties of two novel compounds developed to selectively inhibit the c-Met receptor in antitumor therapeutic interventions. Experimental Design: The pharmacologic properties, c-Met inhibitory activity, and antitumor effects of EMD 1214063 and EMD 1204831 were investigated in vitro and in vivo, using human cancer cell lines and mouse xenograft models. Results: EMD 1214063 and EMD 1204831 selectively suppressed the c-Met receptor tyrosine kinase activity. Their inhibitory activity was potent [inhibitory 50% concentration (IC50), 3 nmol/L and 9 nmol/L, respectively] and highly selective, when compared with their effect on a panel of 242 human kinases. Both EMD 1214063 and EMD 1204831 inhibited c-Met phosphorylation and downstream signaling in a dose-dependent fashion, but differed in the duration of their inhibitory activity. In murine xenograft models, both compounds induced regression of human tumors, regardless of whether c-Met activation was HGF dependent or independent. Both drugs were well tolerated and induced no substantial weight loss after more than 3 weeks of treatment. Conclusions: Our results indicate selective c-Met inhibition by EMD 1214063 and EMD 1204831 and strongly support clinical testing of these compounds in the context of molecularly targeted anticancer strategies. Clin Cancer Res; 19(11); 2941–51. ©2013 AACR.
Collagenases in human synovial fluid
Authors: Edward D. Harris, Donald R. DiBona, Stephen M. Krane
Journal: Journal of Clinical Investigation (1969)

An enzyme which degrades native collagen at neutral pH has been isolated from cultures of rheumatoid synovium in vitro, but little or no collagenolytic activity has been found in homogenates of fresh rheumatoid synovium. Similar to most other mammalian collagenases this synovial enzyme is readily inhibited by serum proteins. Proteins of synovial fluid are derived largely from serum and synovial fluid from noninflamed joints was found to inhibit synovial collagenase; the inhibitor was destroyed by trypsin, but not by hyaluronidase. Inhibitory activity was reduced in approximately one-half of the fluids from patients with rheumatoid arthritis. In a total of nine synovial fluids, collagenolytic activity was detectable. This activity was not present in constant amounts in synovial fluids aspirated at different times from the same patient and tended to vary inversely with the titer of inhibitory proteins. The collagenolytic activity in the synovial fluids from different patients was variably inhibited by serum proteins. Two distinct collagenases were detected in some rheumatoid synovial fluids and separated by gel filtration. One, labeled "B" enzyme, with an estimated molecular weight 20,000-25,000 resembled the collagenase obtained from synovial cultures. The other, labeled "A" enzyme degraded collagen fibrils as well as collagen in solution. Disc electrophoresis on acrylamide gels and electron microscopy of segment long spacing (SLS) aggregates of reaction products of the enzymes at 27 degrees C demonstrated that both "A" and "B" enzymes cleaved collagen molecules at a point three-quarters from the amino terminal end of the molecule. Thus collagen degradation in rheumatoid arthritis could result from the operation of these two collagenases.
PMO-171 A pilot of targeted case finding for hepatitis B virus (HBV) and hepatitis C (HCV) in the British South Asian community
Authors: S Mcpherson, S Moses, M Valappil, S Rehman, C Miller, K Baxter, A Saeed, K Shafiq, M Hudson, M Bassendine
Journal: Gut (2012)

<h3>Introduction</h3> Chronic HBV (cHBV) and HCV (cHCV) are frequent causes of cirrhosis and liver cancer. cHBV and cHCV are prevalent in subjects from South Asian countries and many infected individuals are unaware of their condition. A previous case finding pilot for HBV in the British–Chinese community of the NE of England found that 9% of subjects tested were HBsAg positive.<sup>1</sup> Targeted screening for HBV and HCV is recommended by the AASLD<sup>2</sup> and the European Liver Patients Association<sup>3</sup> in subjects born in endemic areas (HBsAg prevalence ≥2%). However, there are no current UK guidelines. Our aim was to apply AASLD recommendations to British South Asian community of NE of England. <h3>Methods</h3> Members of the NE South Asian community were invited to attend screening sessions at a Newcastle Mosque and the Sunderland Bangladeshi Community Centre. Dry blood spots were obtained by finger prick and tested for HBsAg, HBcAb (Abbott ARCHITECT®) and HCV antibody (Roche + confirmed by Biorad). HBsAg and/or HCV Ab positive individuals were advised to undergo confirmatory testing and be referred for specialist assessment. <h3>Results</h3> To date, 329 subjects were screened in four sessions (median age 39, range 6–83; 75% male). The screened subjects were most frequently born in Bangladesh (49%) followed by Pakistan (36%), the UK (14%) or other countries (6%). 1.8% of subjects were HBsAg positive indicating cHBV. 2.8% of subjects had past infection with HBV (HBsAg negative, HBcAb positive). 1% of subjects were HCV Ab positive (all born in Pakistan). The prevalence of cHBV was 3% for individuals born in Pakistan and 1.5% for those born in Bangladesh. 3% of individuals born in Pakistan were HCV Ab positive. Only 4% of subjects reported previous vaccination against HBV. <h3>Conclusion</h3> Undiagnosed cHBV is prevalent in the South Asian community of NE England, although the prevalence was lower than in the British–Chinese community. These results provide evidence for a targeted case finding programme for HBV and HCV in subjects born in South Asia. <h3>Funding</h3> This study was supported by a Gilead UK and Ireland Fellowship and Livernorth. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>McPherson S</b>, <i>et al. Gut</i> 2011;<b>60</b>(Supp 2):A25. 2. <b>Lok A</b>, McMahon B. <i>Hepatology</i> 2009;<b>50</b>:1–36. 3. <b>Piorkowsky N</b>. <i>J Hepatol</i> 2009;<b>51</b>:1068–73.
Cognitive Impairment in Adolescents With Schizophrenia
Authors: John T. Kenny, Lee Friedman, Robert L. Findling, Thomas P. Swales, Milton E. Strauss, John A. Jesberger, S. Charles Schulz
Journal: American Journal of Psychiatry (1997)

OBJECTIVE: The purpose of this study was to determine whether adolescent schizophrenia is characterized by neuropsychological deficits. METHOD: The performance on a battery of neuropsychological tests of 17 adolescents with schizophrenia (mean age=15.71 years) was compared with that of 17 normal adolescents (mean age=15.12 years). RESULTS: Compared with the normal subjects, the patients were impaired on 10 of the 13 measures; larger effect sizes were shown for measures involving working memory and attention than for those involving secondary memory, generative naming, and executive functions. CONCLUSIONS: Adolescents with schizophrenia have generalized cognitive dysfunction, which is most apparent on tests of attention and working memory. (Am J Psychiatry 1997; 154:1613–1615)
Depressive Symptoms, Health Behaviors, and Subsequent Inflammation in Patients With Coronary Heart Disease: Prospective Findings From the Heart and Soul Study
Authors: Hester E. Duivis, Peter de Jonge, Brenda W. Penninx, Bee Ya Na, Beth E. Cohen, Mary A. Whooley
Journal: American Journal of Psychiatry (2011)

Depression has been associated with inflammation in patients with coronary heart disease. However, it is uncertain whether depressive symptoms lead to inflammation or vice versa.The authors evaluated 667 outpatients with established coronary heart disease from the Heart and Soul Study. Depressive symptoms were assessed annually with the 9-item Patient Health Questionnaire. Participants were categorized as having no significant depressive symptoms (score below 10 at all interviews), depressive symptoms (score of 10 or higher) at one interview, or depressive symptoms at two or more interviews. At baseline and 5-year follow-up, fasting blood samples were collected to measure three inflammatory biomarkers: fibrinogen, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP).Of the 667 participants, 443 had no depressive symptoms, 86 had depressive symptoms at one assessment, and 138 had depressive symptoms at two or more annual assessments. Across the three groups, greater depressive symptoms were associated with higher subsequent log-transformed levels of IL-6 and hsCRP, and the association with higher fibrinogen levels approached significance. Baseline inflammation did not predict subsequent depressive symptoms. The association of depressive symptoms with subsequent inflammation levels was eliminated after adjustment for health behaviors associated with depression-physical inactivity, smoking, and higher body mass index.Depressive symptoms predicted higher IL-6 and hsCRP levels among outpatients with coronary heart disease, but higher inflammation levels did not predict subsequent depressive symptoms. The association between depressive symptoms and inflammation was no longer significant after adjustment for health behaviors, which suggests these behaviors may mediate depressive effects.
THE PROMISE AND PITFALLS OF SYSTEMATIC REVIEWS
Authors: Patricia Dolan Mullen, Gilbert Ramírez
Journal: Annual Review of Public Health (2006)

▪ Abstract The systematic review “movement” that has transformed medical journal reports of clinical trials and reviews of clinical trials has taken hold in public health, with the most recent milestone, the publication of the first edition of The Guide to Community Health Services in 2005. In this paper we define and distinguish current terms, point out important resources for systematic reviews, describe the impact of systematic review on the quality of primary studies and summaries of the evidence, and provide perspectives on the promise of systematic reviews for shaping the agenda for public health research. Several pitfalls are discussed, including a false sense of rigor implied by the terms “systematic review” and “meta-analysis” and substantial variation in the validity of claims that a particular intervention is “evidence based,” and the difficulty of translating conclusions from systematic reviews into public health advocacy and practice.