tbuckley/cabot-search huggingface dataset:
Abstract P351: Inflammation and Stroke Risk in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Nancy S Jenny, Peter Callas, Neil A Zakai, Leslie McClure, Suzanne Judd, Brett Kissela, James Meschia, Susan Lakoski, Mary Cushman
Journal: Circulation (2014)

Background: Levels of the pro-inflammatory cytokines interleukin (IL)-6 and IL-8 and the anti-inflammatory cytokine IL-10 are altered in acute stroke patients compared to controls. However, results for IL-10 are inconsistent (higher in stroke patients compared to controls in some studies and decreased in others) and very few studies have examined associations of these biomarkers with risk of incident stroke. Methods: We examined associations of baseline levels of IL-6, IL-8 and IL-10 with stroke risk factors and risk of incident stroke in 1,572 white and black men and women from the REGARDS Study; an observational cohort of 30,239 adults followed for 5 years. Among those without prebaseline stroke, stroke cases (n=592, 53% men, 59% white, mean age 70 years) were compared to a cohort random sample (n=980, 44% men, 58% white, mean age 65 years). We used Cox proportional hazards models to examine associations of biomarkers with incident stroke. Hazard ratios (HR; 95% confidence intervals) for highest compared to lowest quartile for each biomarker are presented. Results: Baseline IL-6 was significantly higher in incident stroke cases compared to the cohort sample (p&lt;0.001) while IL-8 and IL-10 levels did not vary significantly (p&gt;0.05 for both). Adjusting for age, sex and race, IL-6 was higher in blacks compared to whites and higher in current smokers compared to never/former smokers (all p≤0.01). IL-6 was inversely associated with physical activity, alcohol use and education (all p≤0.01). IL-8 and IL-10 did not vary significantly with the risk factors examined. Adjusting for age, sex and race, the HR for risk of incident stroke in those in the highest compared to lowest quartile of IL-6 was 2.4 (1.6-3.4). HRs for IL-8 and IL-10 were 1.5 (1.0-2.1) and 1.4 (1.0-1.9), respectively. Adjusting for Framingham stroke risk factors and history of coronary heart disease, only IL-6 remained significantly associated with stroke risk (HR 2.0; 1.3-3.2). HRs for IL-8 and IL-10 were 1.1 (0.7-1.6) and 1.2 (0.8-1.8), respectively. IL-6 remained significantly associated with stroke risk when C-reactive protein was added to the model (HR 1.7; 1.1-2.7). Associations did not differ by race. Conclusions: In this population-based sample of US black and white adults, IL-6, but not IL-8 or IL-10, was associated with stroke risk factors and risk of incident stroke. Further study is needed on the clinical utility of IL-6 measurement in stroke risk assessment.
Erectile Dysfunction in Obese Men
Authors: Steven H Feinsilver
Journal: JAMA (2004)

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
The antitumor and antimetastasis effect of the oral Multi-target Tumor Growth Inhibitor™, ZK 304709, in pancreatic tumor xenografts
Authors: Gerhard Siemeister, Katharina Detjen, Sanna-Maria Käkönen, Ulrich Lücking, Domink Mumberg, Arne Scholz, Karola Wagner, Bertram Wiedenmann, Klaus Bosslet
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4036 

Tumor-induced neovascularization and the loss of cell cycle control represent a common phenotype for many cancers, including infiltrating ductal adenocarcinomas of the pancreas and neuroendocrine tumors of the gastroenteropancreatic system. This has led to a search for compounds that target the proliferative and angiogenic pathways, in an attempt to discover novel anti-oncogenic therapies. ZK 304709 is a first-in-class, oral Multi-target Tumor Growth Inhibitor™ (MTGI™) that induces apoptosis and tumor cell death via inhibition of cell cycle progression, mRNA synthesis, and tumor-induced angiogenesis. More specifically, at nanomolar concentrations ZK 304709 inhibits CDKs 1, 2, 4, 7 and 9, VEGF-receptor tyrosine kinases (RTKs) 1-3 and PDGF-RTKβ. This multi-targeted profile suggests ZK 304709 is a strong candidate for the treatment of pancreatic tumors. Using a flow cytometric assay, treatment with ZK 304709 was found to produce a blockade of cell cycle progression that was consistent with CDK inhibition. Inhibition of VEGF-induced vascular permeability, as measured by Evans blue dye extravasation (Miles assay) in nude mice, indicated that ZK 304709 blocks the VEGF-RTK system in vivo. Treatment of mice (8-10 per group), bearing subcutaneous or orthotopically implanted MIA PaCa-2 human pancreatic tumors, with ZK 304709 resulted in an inhibition of tumor growth, demonstrating a reduction in primary tumor weight of >80%. This is a 4-8 fold improvement compared with intraperitoneal gemcitabine treatment, which reduced subcutaneously implanted tumors by 42% and orthotopically implanted tumors by only 20%. ZK 304709 treatment of orthotopically implanted tumors also reduced macroscopically visible metastases below detection levels, whereas gemcitabine alone produced 60% of mice without visible metastases. When the two drugs were combined the weight of primary orthotopically implanted Capan-1 tumors was reduced by 92%, and no metastases were visible. In the orthotopically implanted BON human neuroendocrine pancreatic tumor model, ZK 304709 achieved an 80% reduction of primary tumor growth and markedly reduced the incidence of macroscopically visible liver metastases (30% vs 70% for ZK 304709 and control, respectively).Nanomolar concentrations of ZK 304709 demonstrated potency and efficacy in inhibiting the growth and metastasis formation of human pancreatic tumor xenografts, making it a promising potential therapeutic compound for the treatment of pancreatic cancer. ZK 304709 is currently in Phase I clinical trials in patients with advanced solid tumors.
Abstract 1782: The ubiquitin protease UBP43 is a target for KRAS mutant lung cancers
Authors: Lisa Maria Mustachio, Fadzai Chinyengetere, Yun Lu, Shanhu Hu, Masanori Kawakami, Laura J. Tafe, Alexey Danilov, David J. Sekula, Tian Ma, Sarah J. Freemantle, Ethan Dmitrovsky
Journal: Cancer Research (2014)

Abstract KRAS is frequently mutated in human lung cancers. Lung cancers with mutant KRAS are often resistant to current therapies. There is therefore a need to develop new ways to target these tumors with KRAS mutations. We previously found that the protein modification pathway containing the ubiquitin-like interferon-stimulated gene 15 (ISG15) destabilizes cyclin D1 and represses growth and tumorigenicity of lung cancer cells. This study substantially extends that prior work by reporting that inhibition of the ubiquitin protease UBP43, which removes ISG15 from protein substrates, also destabilizes KRAS protein levels. In a screen of murine lung cancer cells with KRAS mutations, the lines with highest KRAS protein levels had the highest levels of UBP43 protein, implying a direct link between UBP43 and KRAS. Stable overexpression of UBP43 in murine lung cancer cells increased cancer cell growth and stability of KRAS protein. In contrast, knockdown of UBP43 in murine and human lung cancer cell lines had the opposite effects on growth and KRAS protein stability. Co-immunoprecipitation experiments established an interaction between ISG15 and both wild-type KRAS and mutant KRAS. UBP43 immunohistochemical staining of human lung cancer cases showed a marked increase in UBP43 expression in KRAS mutant versus KRAS wild-type lung cancers. Preliminary findings in newly engineered mouse models revealed an increase in lung cancers in KRAS mutant/UBP43 wild-type as compared to KRAS mutant/UBP43 null mice. This finding provides a genetic basis for targeting UBP43 in lung cancers. Taken together, these studies broaden the role of UBP43 as an antineoplastic target to include an unmet medical need. This is to combat lung cancers that harbor KRAS mutations. Citation Format: Lisa Maria Mustachio, Fadzai Chinyengetere, Yun Lu, Shanhu Hu, Masanori Kawakami, Laura J. Tafe, Alexey Danilov, David J. Sekula, Tian Ma, Sarah J. Freemantle, Ethan Dmitrovsky. The ubiquitin protease UBP43 is a target for KRAS mutant lung cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1782. doi:10.1158/1538-7445.AM2014-1782
Infopoints: Online appointment booking to rapid access chest pain clinic
Authors: I. Findlay
Journal: BMJ (2000)

to hospital were relatively short and use of the equipment was low; had each health centre seen 12 patients a week and the patients lived an average of 40 km from the hospital, teledermatology would have been as cheap.Other factors, such as cheaper equipment, would also improve the relative economics for telemedicine.Nevertheless it is clear that, although real time teledermatology is both clinically effective and economic in the appropriate circumstances, it is not likely to be useful in large cities, except possibly for secondary-to-tertiary consulting or for educational use.Its place in the overall management of dermatology patients from primary care, and indeed the place of pre-recorded teledermatology ("store-andforward") remains to be established in future trials.
Abstract P143: Hemoglobin A1C Screening in 31546 Adolescent Blood Donors
Authors: Maria Odette Gore, Stephen J Eason, Colby R Ayers, Aslan Turer, Amit Khera, James A de Lemos, Darren K McGuire, Merlyn Sayers
Journal: Circulation (2014)

Objective: While the global epidemic of diabetes mellitus in adults is well documented, there are few reliable estimates of the prevalence of diabetes and prediabetes in adolescents in the United States. We conducted systematic hemoglobin A1C (HbA1C) screening in a very large adolescent blood donor population. Methods: A screening program was implemented in which HbA1C was measured at the time of blood donation among 31,546 volunteer high-school blood donors, 16-19 years of age, who participated in school blood drives conducted by Carter BloodCare, the largest independent blood program in Texas, between 2011 and 2013. The main study measures were the prevalence of HbA1C in the prediabetes range, 5.7-6.4% (39-46 mmol/mol) and in the diabetes range, ≥ 6.5% (≥ 48 mmol/mol), in the overall cohort as well as stratified by sex, race/ethnicity, and sociodemographic characteristics. Results: In the overall cohort, the prevalence of HbA1C in the prediabetes range was 11.0% (95% CI 10.7, 11.4), and the prevalence of HbA1C in the diabetes range was 0.53% (95% CI, 0.46, 0.62). The prevalence of HbA1C ≥ 5.7% (including prediabetes and diabetes) was higher in boys compared with girls (15.7% vs.7.9%, P&lt;0.001), and was especially high in race/ethnic minorities (32.7%, 19.7%, 13.1%, respectively in Blacks, Asians, Hispanics) compared with 8.0% in Whites (p&lt;0.001 for each vs. Whites). In analyses of cardiovascular risk factors stratified by HbA1C categories, higher total cholesterol and systolic and diastolic blood pressure were observed in donors with HbA1C in the prediabetes and diabetes range (P trend &lt; 0.001 for all, Table ). Conclusions: HbA1C values in the prediabetes or diabetes range are common among adolescent blood donors, particularly among boys and ethnic minorities. Blood donation programs can be used as a valuable portal for public health screening, and may provide the opportunity for targeted public health interventions, triaging of donors to medical care, and research programs for community-based participatory interventions.
MI with normal coronaries in toxic cardiomyopathy.
Authors: T J Regan, C B Moschos, A B Weisse
Journal: Circulation (1977)

The effects of individualizing the Kd 2 or decreasing values for Kw and KR3 are reflected in the reduced slope of the regression lines.The recently recommended parameters markedly reduced the magnitude of estimates from serum enzyme measurements.However, they did not improve the correlation between those estimates and myocardial CPK depletion.
Low Density Lipoprotein
Authors: A. Sniderman, D. Thomas, D. Marpole, B. Teng
Journal: Journal of Clinical Investigation (1978)

The mechanism(s) by which cholesterol returns to the splanchnic bed from peripheral tissues are not well understood. To study this phenomenon in fasting man, lipoproteins were isolated from plasma obtained from hepatic vein and aorta. Cholesterol content of each lipoprotein class was determined and arteriovenous (AV) differences could be calculated for each patient. The results in the first 24 patients indicated splanchnic secretion of very low density lipoprotein cholesterol (mean AV difference - 3 mg/100 ml, P < 0.01), but not significant AV difference for total cholesterol, high density lipoprotein cholesterol, or low density lipoprotein (LDL) B protein. In contrast, for LDL (d 1.006-1.063 g/ml), there was significant uptake of cholesterol across the AV bed +8 mg/100 ml, P < 0.0002). In a further 15 patients, similar samples were obtained and intermediate density lipoprotein isolated at d 1.006-1.019 g/ml and LDL at 1.019-1.063 g/ml. The AV difference previously noted could now be localized to the 1.019-1.063 cholesterol ester moiety (+8 mg/100 ml, P < 0.0005). In the final 14 patients, the LDL cholesterol AV difference was again confirmed and shown to be unrelated to heparin. As well, there was secretion of triglyceride in the hepatic vein LDL. These quantitative data obtained in man raise the possibility that LDL rather than high density lipoprotein transports cholesterol ester to the splanchnic bed.
Abstract 11059: Role of Sirtuin 6 in Macrophage Polarization and Cardiac Repair in Diabetes
Authors: Rajarajan A Thandavarayan, Darukeshwara Joladarashi, Sahana S Babu, Garikipati V Srikanth, Alexander R Mackie, Suresh K Verma, Erin E Vaughan, Raj Kishore, Prasanna Krishnamurthy
Journal: Circulation (2014)

Clinical and experimental studies provide evidence that metabolic and inflammatory pathways are functionally interconnected to cardiovascular diseases. Dynamic changes in macrophage activation [classical M1 activation (promote inflammation) or alternative M2 activation (promote wound healing)], in response to various stress signals, modulate cardiac physiopathology in diabetes. Sirtuin 6 (SIRT6), a NAD-dependent nuclear deacetylase plays an important role in genomic stability, cellular metabolism, stress response and aging. However, the mechanism by which SIRT6 activity affects macrophage phenotype and cardiac function in diabetes is still unexplored. Mouse bone marrow-derived macrophages (BMM) exposed to high glucose (HG, 25mM D-glucose) showed reduced expression of SIRT6 as compared to low glucose (LG, 5mM D-glucose)- and osmotic control (OC, 5mM D-glucose+20mM D-mannitol)-treated cells, associated with increased expression of proinflammatory cytokine and transcription factors (NFkb, c-JUN, FOXO, SP1 and STAT1). In addition, SIRT6 level was reduced in peritoneal macrophages of both diabetic models (streptozotocin-induced and db/db mice) as compared to non-diabetic mice. SIRT6 knockdown in RAW 264.7 cells exaggerated inflammatory response when exposed to HG. In contrast, IL-4-induced increase in mRNA expression of macrophage M2 phenotype markers like Arg1, Chi4l4, Retnla and IRS-2, but not IRS-1 expression was repressed suggesting that alternative macrophage (M2) phenotype was defective in SIRT6 deficient BM-macrophages under HG condition. SIRT6 protein expression was low in myocardial infarction-induced (MI) and diabetes-affected hearts. Interestingly, mice receiving intramyocardial injection of SIRT6-deficient macrophages showed further deterioration in left ventricular function, post-MI. Taken together, these data highlight a role for SIRT6 in regulating the balance of M1/M2 polarization, therefore, modulate macrophage mediated cardiac repair and regeneration in numerous inflammatory disease states including diabetes
Abstract 3527: YYEI motif is critical to oncogenicity of 14-3-3 proteins
Authors: Wen-Hsin Chang, Ching-Hsien Chen, Qi-Sheng Hong, Jian-Wei Chen, Sung-Liang Yu, Chiung-Tong Chen
Journal: Cancer Research (2014)

Abstract 14-3-3 family consists of seven highly conserved isoforms and most of them are identified as oncogenes in various types of cancer except for 14-3-3σ, a well-known tumor suppressor. To clarify the suppressor characteristic of 14-3-3σ divergent from others, we found that the major difference between the other oncogenic members and 14-3-3σ by protein alignment was an amino acid substitution (Y180H) by which the SH2-binding motif (YYEI) is disrupted and cannot be phosphorylation. Thus, we generated a H180Y 14-3-3σ mutant and investigated the impact of the acquired YYEI motif on the tumor suppression. First, we found that 14-3-3σ decreased cancer invasion. Surprisingly, the H180Y mutant not only enhanced cell invasion but increased cell viability. Meanwhile, the interaction between H180Y mutant and Src was higher than wild type. It indicates one amino acid substitution switches 14-3-3σ from tumor suppressor to oncogene. Hence, the YYEI motif might be important for the oncogenicity of other 14-3-3 proteins. Indeed, we demonstrated that 14-3-3ζ interacted with Src through Y178 phosphorylation, which is crucial for the binding of 14-3-3ζ with Src-SH2 domain. Owing to the importance of Y178 phosphorylation in the 14-3-3ζ/Src interaction, we introduced the Y178F 14-3-3ζ mutant to lung cancer cells and confirmed that Y178 phosphorylation is important for the increase of invasion and viability. Furthermore, we also revealed an amino acid switch of 14-3-3σ from YYEI to HYEI during evolutionary progression. Taken together, our findings suggest that YYEI motif is essential for 14-3-3 proteins to interact with Src and to regulate Src-mediated cell functions. Citation Format: Wen-Hsin Chang, Ching-Hsien Chen, Qi-Sheng Hong, Jian-Wei Chen, Sung-Liang Yu, Chiung-Tong Chen. YYEI motif is critical to oncogenicity of 14-3-3 proteins. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3527. doi:10.1158/1538-7445.AM2014-3527
Study of Optimal Perimetric Testing In Children (OPTIC)
Authors: Dipesh E. Patel, Phillippa M. Cumberland, Bronwen C. Walters, Isabelle Russell-Eggitt, Mario Cortina-Borja, Jugnoo S. Rahi
Journal: Ophthalmology (2015)

We sought to define normative visual field (VF) values for children using common clinical test protocols for kinetic and static perimetry.Prospective, observational study.We recruited 154 children aged 5 to 15 years without any ophthalmic condition that would affect the VF (controls) from pediatric clinics at Moorfields Eye Hospital.Children performed perimetric assessments in a randomized order using Goldmann and Octopus kinetic perimetry, and Humphrey static perimetry (Swedish Interactive Thresholding Algorithm [SITA] 24-2 FAST), in a single sitting, using standardized clinical protocols, with assessment by a single examiner. Unreliable results (assessed qualitatively) were excluded from the normative data analysis. Linear, piecewise, and quantile mixed-effects regression models were used. We developed a method to display age-specific normative isopters graphically on a VF plot to aid interpretation.Summary measures and graphical plots describing normative VF data for 3 common perimetric tests.Visual field area increased with age on testing with Goldmann isopters III4e, I4e, and I2e (linear regression; P < 0.001) and for Octopus isopters III4e and I4e (linear regression; P < 0.005). Visual field development occurs predominately in the inferotemporal field. Humphrey mean deviation (MD) showed an increase of 0.3 decibels (dB; 95% CI, 0.21-0.40) MD per year up to 12 years of age, when adult MD values were reached and thereafter maintained.Visual field size and sensitivity increase with age in patterns that are specific to the perimetric approach used. These developmental changes should be accounted for when interpreting perimetric test results in children, particularly when monitoring change over time.
Hypoxia Modulates the Phenotype of Osteoblasts Isolated From Knee Osteoarthritis Patients, Leading to Undermineralized Bone Nodule Formation
Authors: Joan Chang, Sonya G. Jackson, John Wardale, Simon W. Jones
Journal: Arthritis & Rheumatology (2014)

To investigate the role of hypoxia in the pathology of osteoarthritic (OA) bone by exploring its effect on the phenotype of isolated primary osteoblasts from patients with knee OA.OA bone samples were collected at the time of elective joint replacement surgery for knee or hip OA. Normal bone samples were collected postmortem from cadaver donors. Primary osteoblasts were isolated from knee OA bone chips and cultured under normoxic or hypoxic (2% O2 ) conditions. Alkaline phosphatase activity was quantified using an enzymatic assay, and osteopontin and prostaglandin E2 (PGE2 ) production was assayed by enzyme-linked immunosorbent assay. Total RNA was extracted from bone and osteoblasts, and gene expression was profiled by quantitative reverse transcription-polymerase chain reaction.Human OA bone tissue sections stained positively for carbonic anhydrase IX, a biomarker of hypoxia, and exhibited differential expression of genes that mediate the vasculature and blood coagulation as compared to those found in normal bone. Culture of primary osteoblasts isolated from knee OA bone under hypoxic conditions profoundly affected the osteoblast phenotype, including the expression of genes that mediate bone matrix, bone remodeling, and bone vasculature. Hypoxia also increased the expression of cyclooxygenase 2 and the production of PGE2 by OA osteoblasts. Osteoblast expression of type II collagen α1 chain, angiopoietin-like 4, and insulin-like growth factor binding protein 1 was shown to be mediated by hypoxia-inducible factor 1α. Chronic hypoxia reduced osteoblast- mineralized bone nodule formation.These findings demonstrate that hypoxia can induce pathologic changes in osteoblast functionality consistent with an OA phenotype, providing evidence that hypoxia is a key driver of OA pathology.