tbuckley/cabot-search huggingface dataset:
Metabolic Syndrome and the Risk of Mild Cognitive Impairment and Progression to Dementia
Authors: Tze Pin Ng, Liang Feng, Ma Shwe Zin Nyunt, Lei Feng, Qi Gao, May Li Lim, Simon L. Collinson, Mei Sian Chong, Wee Shiong Lim, Tih Shih Lee, Philip Yap, Keng Bee Yap
Journal: JAMA Neurology (2016)

<h3>Importance</h3> The association of the metabolic syndrome (MetS) and component cardiovascular risk factors with the risk of developing mild cognitive impairment (MCI) and MCI progression to dementia is not well established. <h3>Objective</h3> To investigate the association of the MetS and its component cardiovascular risk factors with the incidence of MCI and its progression to dementia. <h3>Design, Setting, and Participants</h3> Prospective longitudinal study from September 1, 2003, through December 31, 2009, in communities in 5 districts in the South East region of Singapore. Study participants were a population-based sample of 1519 cognitively normal adults 55 years and older. <h3>Main Outcomes and Measures</h3> Prespecified outcomes were incident MCI and MCI progression to dementia. <h3>Results</h3> The study cohort comprised 1519 participants. Their mean (SD) age was 64.9 (6.8) years, and 64.8% (n = 984) were female. Baseline characteristics associated with an increased risk of incident MCI were MetS (hazard ratio [HR], 1.46; 95% CI, 1.02-2.09), central obesity (HR, 1.41; 95% CI, 1.01-1.98), diabetes mellitus (HR, 2.84; 95% CI, 1.92-4.19), dyslipidemia (HR, 1.48; 95% CI, 1.01-2.15), and 3 or more component cardiovascular risk factors (HR, 1.58; 95% CI, 1.13-2.33). Baseline characteristics associated with an increased risk of MCI progression to dementia were MetS (HR, 4.25; 95% CI, 1.29-14.00), diabetes mellitus (HR, 2.47; 95% CI, 1.92-4.19), and 3 or more component cardiovascular risk factors (HR, 4.92; 95% CI, 1.39-17.4). <h3>Conclusions and Relevance</h3> The MetS was associated with an increased incidence of MCI and progression to dementia. Identifying individuals with diabetes mellitus or the MetS with or without MCI is a promising approach in early interventions to prevent or slow progression to dementia.
CENTENARIANS IN THE UNITED STATES.
Journal: JAMA (1903)

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
Abstract 15093: Insulin-Like Growth Factor 1 Regulates Lipid Accumulation in Macrophages - A Potential Mechanism for Insulin-Like Growth Factor 1 Mediated Atheroprotection
Authors: Yusuke Higashi, Shaw-Yung Shai, Sergiy Sukhanov, Catherine Kim, Patricia Snarski, Patrice Delafontaine
Journal: Circulation (2013)

Lipid accumulation and foam cell formation is a hallmark of atherogenesis, whereas apoptosis of foam cells leads to necrotic core formation and plaque vulnerability. Insulin-like growth factor-1 (I...
Abstract 20574: Selective Activation of the PI3K/Akt Pathway With the Insulin Mimetic Demethylasterriquinone B1 Reverses Neuroinflammatory-Mediated Blood-Brain Barrier Dysfunction in Mice
Authors: Richard S Beard, Ricci J Haines, Jonathan W Overstreet, Jamie E Meegan, Mack H Wu, Sarah Y Yuan
Journal: Circulation (2014)

Blood-brain barrier (BBB) dysfunction is a hallmark of neuroinflammation brought on by pathologies such as stroke and amyloid angiopathy. Inflammatory cytokines that act directly on cerebral endothelium can impair tight junction (TJ) stability. We previously identified a mechanism for IL-1β-mediated dysfunction involving inactivation of the PI3K/Akt pathway, activation of the transcription factor FoxO1, and FoxO1-dependent transcriptional repression of the TJ gene claudin-5 (Cldn5). Here we used an insulin mimetic, Demethylasterriquinone B1 (DMAQ-B1), to test the hypotheses that targeted activation of the PI3K/Akt pathway: 1) enhances cerebral endothelial barrier function, 2) reverses IL-1β-mediated dysfunction and 3) attenuates neuroinflammation-induced BBB dysfunction. In Vitro: Primary cerebral microvascular endothelial cells (CMVECs) were grown in collagen-coated dishes, transwell inserts (0.4 μm pores), or ECIS Arrays (Applied Biophysics). Culture media was conditioned with vehicle control, IL-1β (100 ng/mL), and/or DMAQ-B1 (2.5-10 μM). DMAQ-B1 dose-dependently activated Akt (increased pT308), inactivated FoxO1 (decreased nuclear localization), increased Cldn5 expression (WB, ICC), increased transendothelial electrical resistance (TER), and decreased CMVEC monolayer permeability (Ps). Akt silencing (siRNA), PI3K inhibition (LY294002), or IL-1β treatment downregulated Cldn5 and induced CMVEC barrier dysfunction. DMAQ-B1 (5 μM) reversed IL-1β-mediated Akt inactivation, FoxO1 activation, Cldn5 downregulation and CMVEC barrier dysfunction. In Vivo: We used a murine model of neuroinflammation, experimental autoimmune encephalomyelitis (EAE). Cerebral microvascular enriched fractions from EAE-induced mice had less pT308 Akt, increased FoxO1 nuclear accumulation, and decreased Cldn5 expression compared to control. Decreased Cldn5 expression and increased BBB hyperpermeability (sodium fluorescein extravasation) observed in EAE-induced mice was attenuated by 24 hour DMAQ-B1 (5 mg/kg; oral gavage) treatment. These results indicate that promoting PI3K/Akt pathway activation with DMAQ-B1 during neuroinflammatory pathologies may provide a novel therapeutic approach to attenuate BBB dysfunction.
Immunologic Relationship Between Breast Carcinoma and Benign Breast Disease as Detected by the Leukocyte Migration Inhibition Assay2
Authors: G. B. Cannon, J. L. McCoy, L. J. Jerome, R. Reddick, C. Alford, V. Tinley, R. B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Immunologic Relationship Between Breast Carcinoma and Benign Breast Disease as Detected by the Leukocyte Migration Inhibition Assay Get access G. B. Cannon, G. B. Cannon 3Department of Immunology. Litton Bionetics. Inc.. 5516 Nicholson Lane. Kensington. Md. 20795 Search for other works by this author on: Oxford Academic PubMed Google Scholar J. L. McCoy, J. L. McCoy 4Laboratory of Immunodiagnosis. National Cancer Institute. National Institutes of Health. Public Health Service. U.S. Department of Health. Education. and Welfare. Bethesda. Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar L. J. Jerome, L. J. Jerome 3Department of Immunology. Litton Bionetics. Inc.. 5516 Nicholson Lane. Kensington. Md. 20795 Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Reddick, R. Reddick 5Department of Pathology. National Cancer Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar C. Alford, C. Alford 6Department of Surgery. George Washington University Hospital. Washington. D.C. 20037. Search for other works by this author on: Oxford Academic PubMed Google Scholar V. Tinley, V. Tinley 6Department of Surgery. George Washington University Hospital. Washington. D.C. 20037. Search for other works by this author on: Oxford Academic PubMed Google Scholar R. B. Herberman R. B. Herberman 4Laboratory of Immunodiagnosis. National Cancer Institute. National Institutes of Health. Public Health Service. U.S. Department of Health. Education. and Welfare. Bethesda. Md. 20014. 7We thank the Data Processing Department. Litton Bionetics. Inc.. for preparation of the manuscript. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 5, November 1978, Pages 1181–1186, https://doi.org/10.1093/jnci/61.5.1181 Published: 01 November 1978 Article history Received: 02 September 1977 Revision received: 15 May 1978 Accepted: 15 June 1978 Published: 01 November 1978
Pathogenic Autoantibodies in Patients with Severe Asthma and Sputum Eosinophils
Authors: Manali Mukherjee, David Bulir, Katherine Radford, Brenda Helpard, Melanie Kjarsgaard, Elizabeth A. Jacobsen, Sergei I. Ochkur, James J. Lee, Paige Lacy, James Mahony, Parameswaran K. Nair
Journal: Journal of Allergy and Clinical Immunology (2016)
Cardiac Dysfunction in the Trastuzumab Clinical Experience
Authors: James Speyer
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.5.1156 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11870153 Cardiac Dysfunction in the Trastuzumab Clinical Experience James SpeyerxJames SpeyerSearch for articles by this author Show More New York University Cancer Institute, New York University Medical Center, New York, NY https://doi.org/10.1200/JCO.2002.20.5.1156 Full Text PDF Figures and Tables "Cardiac Dysfunction in the Trastuzumab Clinical Experience." Journal of Clinical Oncology, 20(5), pp. 1156–1157© 2002 by American Society of Clinical Oncology
Effects of fractionated irradiation of endocrine aspects of testicular function.
Authors: E Shapiro, T J Kinsella, R W Makuch, B A Fraass, E Glatstein, S A Rosenberg, R J Sherins
Journal: Journal of Clinical Oncology (1985)

We have examined the hormonal alterations of testicular function in 27 males (14 to 67 years of age) with soft-tissue sarcoma who were treated with surgery and high-dose radiation to the tumor bed. The testicular dose from scatter radiation ranged from 1 to 2,500 rad. There was a dose-dependent increase in the median per patient difference from baseline in serum follicle-stimulating hormone (FSH) values following irradiation, with the maximal difference seen at 6 months. Recovery of serum FSH level was biphasic with a decline in the median difference in values between 6 and 12 months, followed by a gradual descent toward baseline. Only patients receiving less than 50 rad show early complete recovery 12 months after radiation therapy. Radiation injury also induced dose-dependent increases in serum luteinizing hormone (LH) concentration, with the maximal median difference from baseline level occurring at 6 months. Only those patients receiving greater than 200 rad showed statistically significant LH changes from baseline levels at each time interval up to 30 months. No significant changes were observed in total testosterone values. These data provide quantitative guidelines for predicting seminiferous tubule injury and germ cell depletion in men exposed to fractionated radiation. The effects on seminiferous tubule and Leydig cell function, as judged by serum FSH and LH concentrations, suggest that subtle Leydig cell dysfunction, in addition to germ cell depletion, may also occur at exposures greater than 200 rad.
ON THE USE OF NITRO-SULPHURIC ACID IN CHOLERA AND DIARRHOEA
Authors: W.J. Anderson
Journal: BMJ (1853)

Nov. 4, Scummr." Whenever the amme is like the apriu, we ought to expect profue perspirtions in feverS."Aph.vi.)Iff the vinier have been dry and northerly, and tShe sprng rainy and southerly, of necessity there will be acute fevers, dis of the eyes and dysentery in the summer, especially in the persons of women and men who are of a humid na- ture (sebaceous complexioned)."(Aph.xii.) "In sum?. mer, some of these diseases (referring to those mentioned under Spring), as well as continued fevers, ardent and tertian, much vomiting, diarrhea, ophthalmius, gangrene (erwdS6s) of the genitals, and sudamina (1'puc or Thpw7ap.a)." (Aph.xxii.)Autumn."Autumn is obnoxious to consumptive per- sons."(Aph.x.) "In autumn, diseases are most acute, and altogether most fatal."(Aph.ix.) "1 If it (the au- tumn) be northerly and dry, it is favourable to persons whose systems are of a moist character, as well as to women; but, in other instances, there will be diseases of the eyes, unat- tended with discharge, acute fevers, chronic coryza, and, in some instances, hypochondriacism."(Aph.xiv.) "As to
The hemodialysis prescription and cost effectiveness. Renal Physicians Association Working Committee on Clinical Guidelines.
Authors: J C Hornberger
Journal: Journal of the American Society of Nephrology (1993)

Case-mix adjusted mortality rates for patients undergoing hemodialysis for ESRD increased during the 1980s, despite the introduction of advanced dialysis technologies. Variations in dialysis practices suggest that excess mortality may be caused by inadequate uremic-toxin clearances. Cost-effectiveness analysis was used to assess whether attempts to improve uremic-toxin clearance are cost effective, assuming that these therapies are clinically effective. The medical literature was surveyed by the use of MEDLINE to assess the likelihood of clinical outcomes on the basis of the type of treatment given to the patient. Options considered in the model were delivered fractional urea clearance (Kt/V), dialysis-treatment duration, type of dialyzer membrane, dialysate, and ultrafiltration. Clinical outcomes included in the model were survival, severity of uremic symptoms, hospital days per year, and intradialytic hypotension and symptoms. Lifetime costs were calculated from data collected from a northern California dialysis center and abstracted from the literature. In the base-case scenario, it was assumed that increasing Kt/V to levels greater than 1 was effective in reducing morbidity and mortality. Under these assumptions, outpatient cost increased significantly, but the cost effectiveness of Kt/V equal to 1.5 was less than $50,000 per quality-adjusted life-year saved. These calculations indicate that, if higher levels of Kt/V prove clinically effective, they are also cost effective.
Pharmacokinetics, safety, and efficacy of subcutaneous versus intravenous rituximab plus chemotherapy as treatment for chronic lymphocytic leukaemia (SAWYER): a phase 1b, open-label, randomised controlled non-inferiority trial
Authors: Sarit Assouline, Valeria Buccheri, Alain Delmer, Gianluca Gaidano, Marek Trneny, Natalia Berthillon, Michael Brewster, Olivier Catalani, Sai Li, Christine McIntyre, Pakeeza Sayyed, Xavier Badoux
Journal: The Lancet Haematology (2016)
Motifs of cadherin- and fibronectin type III-related sequences and evolution of the receptor-type-protein tyrosine kinases: sequence similarity between proto-oncogene ret and cadherin family.
Authors: K Kuma, N Iwabe, T Miyata
Journal: Molecular Biology and Evolution (1993)

Immunoglobulin (Ig)-, fibronectin type III (FN-III)-, and cadherin-related sequences are often found in multiple repeats in the extracellular regions of various cell adhesion molecules. The amino acid sequences of 82 different cadherin-like repeats from 13 known members of the cadherin superfamily were compared for six highly conserved regions, and a frequency matrix represented as amino acids versus position matrix was calculated based on the alignment. With the frequency matrix, further members of the cadherin superfamily were searched for in the protein data base. It was found that the ret protein, a receptor-type-protein tyrosine kinase, contains cadherin-like repeats in the extracellular region. A similar analysis was also carried out for the FN-III superfamily. Nine receptor-type-protein tyrosine kinases were shown to exhibit significant similarities, in terms of sequence, with known FN-III-like repeats. Several receptor-type-protein tyrosine kinases have already been reported to have Ig-like repeats in their extracellular regions. Thus these receptor-type-protein tyrosine kinases--together with the remaining receptors, whose structures are not yet characterized--may be classified into at least four distinct groups based on the structural differences in the extracellular domains. A molecular phylogenetic tree inferred from the shared kinase domains of these receptor-type-protein tyrosine kinases revealed a close relationship between the branching patterns and the grouping based on the structural differences of the extracellular region.
Molecular profiling of breast cancer resistance protein (BCRP): A guide to individualized therapy in upper gastro-intestinal malignancies
Authors: Anubha Bharthuar, Thaer Khoury, Maria Baer, Jennifer Black, Alan Oseroff, Nikhil Khushalani, Hector Nava, Renuka Iyer
Journal: Clinical Cancer Research (2008)

B9    Introduction:  Breast cancer resistance protein (BCRP/MXR/ABCG2) is an ATP binding cassette efflux protein expressed on cancer cells that plays a crucial role in multi-drug tumor resistance. Taxanes, irinotecan and photodynamic therapy using photosensitizers such as 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) are palliative measures used in patients with upper gastro-intestinal (UGI) cancers. These drugs are substrates / modulators of multidrug resistance protein such as BCRP. We performed this pilot study to analyze BCRP expression in esophageal and gastric cancers from a randomly selected series of patients.   Methods:  With IRB approval,  paraffin embedded tumor blocks of esophageal and gastric cancer patients diagnosed between 1998 and 2002 at our institute were obtained. Immunohistochemical staining was done using specific murine monoclonal antibody to BCRP, mAb BXP-21 and BXP-34. Slides were read as strongly positive (>10% of cells), intermediate ( Results:  Ten of the 19 patients (52%) examined expressed BCRP [strong (n=6) and intermediate (n=4)]. Eight of ten positive cases had membranous BCRP expression while five had cytoplasmic expression (3/10 were positive for both). There was no difference in average survival in BCRP positive (37.5 months) versus negative patients (27.8 months). One patient received HPPH photodynamic therapy but had poor response and relapsed within 6 months (40% BCRP). One of three patients who received a Taxane had strong (30%) BCRP expression and had poor response to chemotherapy.   Conclusions:  BCRP multidrug resistance protein expression is seen in esophageal, gastro-esophageal junction (GEJ) and gastric cancers. Evaluation of BCRP expression in larger subset is ongoing and will be correlated with response to HPPH, taxanes or irinotecan, and other chemotherapies that may be substrates / modulators of BCRP. Successful correlation would allow rational selection of chemotherapies and photosensitizers (Photofrin instead of HPPH).  Furthermore, BCRP expression can be decreased by epidermal growth factor receptor (EGFR) inhibitors, raising the question of whether treatment with an EGFR inhibitor  could improve clinical outcomes by sensitizing BCRP-positive cancers to therapeutic agents that are BCRP substrates.
Integrated self-assembling drug delivery system possessing dual responsive and active targeting for orthotopic ovarian cancer theranostics
Authors: Chun-Jui Lin, Chen-Hsiang Kuan, Li-Wen Wang, Hsi-Chin Wu, Yunching Chen, Chien-Wen Chang, Rih-Yang Huang, Tzu-Wei Wang
Journal: Biomaterials (2016)
Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum
Authors: Timothy Hardy, Fiona Oakley, Quentin M. Anstee, Christopher P. Day
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction in the Western world and is increasing owing to its close association with obesity and insulin resistance. NAFLD represents a spectrum of liver disease that, in a minority of patients, can lead to progressive nonalcoholic steatohepatitis (NASH), fibrosis, and ultimately hepatocellular carcinoma and liver failure. NAFLD is a complex trait resulting from the interaction between environmental exposure and a susceptible polygenic background and comprising multiple independent modifiers of risk, such as the microbiome. The molecular mechanisms that combine to define the transition to NASH and progressive disease are complex, and consequently, no pharmacological therapy currently exists to treat NASH. A better understanding of the pathogenesis of NAFLD is critical if new treatments are to be discovered.
How Hypertrophic Cardiomyopathy Became a Contemporary Treatable Genetic Disease With Low Mortality
Authors: Barry J. Maron, Ethan J. Rowin, Susan A. Casey, Martin S. Maron
Journal: JAMA Cardiology (2016)

Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease encumbered throughout much of its almost 60-year history by a large measure of misunderstanding and the perception of a grim outcome without effective treatment options. However, it is now apparent that the majority of patients affected with HCM can achieve normal or near-normal life expectancy without disability, and usually do not require major treatment interventions. Nevertheless, for those patients with HCM who are at risk for (or experience) disease-related complications, a constellation of comprehensive nonpharmacologic management strategies have evolved over the last 15 years, altering the natural history and disease course for many, including implantable defibrillators, heart transplant, external defibrillation/therapeutic hypothermia, advances in surgical myectomy, and alcohol ablation. In particular, expanded contemporary risk stratification strategies have led to a more reliable selection of patients likely to achieve primary prevention of sudden death with implantable defibrillators. Most recently, large cohort studies using current management strategies and therapeutic measures have shown that it is now possible to achieve significantly improved survival with a low HCM-related mortality of 0.5% per year across all ages, and including children and young adults characteristically with the most aggressive disease course. These clinical management initiatives, instituted by the practicing cardiology community, have succeeded in preserving life and restoring an active lifestyle for thousands of patients with HCM, while providing many with a measure of reassurance and a reasonable expectation for an extended (if not normal) life span.
Safety and Efficacy Of Ferumoxytol For The Episodic Treatment Of Iron Deficiency Anemia In Patients With a History Of Unsatisfactory Oral Iron Therapy: Results Of a Phase III Open-Label, Six Month Extension Study
Authors: Naomi V Dahl, Gloria Lau, Kristine Bernard, Zhu Li, Pallabi De, Lee F. Allen, William Strauss
Journal: Blood (2013)
Types of patients served by various providers of outpatient care in CMHCs
Authors: C Windle, P J Poppen, J W Thompson, K Marvelle
Journal: American Journal of Psychiatry (1988)

Representative community mental health center (CMHC) survey data showed that psychiatrists differed from other CMHC providers of mental health services by serving the more seriously impaired patients who are admitted and readmitted to outpatient services. Psychiatrists also shared more outpatients with providers from other disciplines than providers in other disciplines shared with one another. The results are consistent with previous research on differences between disciplines and with the flight of psychiatrists from CMHCs but cast doubt on the hypothesis that psychiatrists see sicker patients than psychologists see because of differences in reimbursement between the two disciplines.