tbuckley/cabot-search huggingface dataset:
482. Design and Production of Peptide Transfecting Agents Using Recombinant TAT-Mu-NLS Sequences
Authors: Y. Ramadas, Madhusudhana N. Rao, Vijaya Gopal
Journal: Molecular Therapy (2004)

Peptide-based DNA carriers have recently been used for transfection. These designer peptides carry motifs for binding DNA and also nuclear localization and are expected to achieve transfection in non-dividing cells. As an alternative to chemical synthesis of these peptides, we have attempted to design genes to overproduce the peptide using recombinant methods. We believe by such an approach, several permutations of DNA binding motifs, nuclear localization sequences (NLS), protein transduction domains and cell-specific peptide ligands could be generated. Keeping this perspective in view, we have generated recombinant fusion constructs by cloning the cDNA of the Mu peptide and the (NLS) into the bacterial expression vector pTAT (trans activating protein). The pTAT vector harbors an N-terminal histidine leader followed by eleven amino acid TAT protein transduction domain (PTD). Mu, a DNA condensing peptide from the adenoviral core protein, is of nineteen amino acids, MRRAHHRRRRASHRRNRGG, twelve of which are basic residues In addition, in yet another construct, we have also incorporated three tandem copies of the NLS (DPKKKRKV) 3 of the SV40 large T antigen and fused it at the C terminus of TAT/TAT-Mu with the idea of increasing the efficiency of translocation into the nucleus. These constructs are expressed as fusion proteins having an N-terminal 6-histidine leader followed by TAT (PTD)/NLS/Mu sequences with intervening linker regions to confer flexibility. The plasmid constructs have been verified for DNA sequence integrity and then transformed into the host expression BL21 (DE3) pLysS bacterial strain. The his-tag protein has been expressed and purified using nickel affinity chromatography. We have also generated similar DNA constructs as GST fusions in the plasmid pGEX2T to facilitate protein purification. Purified peptides were obtained after thrombin cleavage. We have obtained 2.5mg of the fusion protein from a one-liter culture. Initial characterization of the TAT-Mu protein shows the ability of the fusion protein to bind plasmid DNA as verified by gel-shift assays. Transfection assays into COS cells with Cationic Liposome based Peptide: pCMVLuc DNA complexes (LPD) resulted in higher reporter gene expression than in the absence of peptide and also when compared to commercial formulations namely lipofectin and DOTMA (N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride). Further characterization of these fusions peptides is in progress to test its utility both in vitro and in vivo.
Abstract 15483: Regenerative Effects of Exosomes Secreted by Cardiospheres in a Rat Model of Chronic Myocardial Infarction Are Mimicked by Exosome-primed Fibroblasts
Authors: Eleni Tseliou, Joseph Fouad, Geoffrey de Couto, Ryan Middleton, Liu Weixin, Jackelyn Valle, Ahmed Ibrahim, Eduardo Marbán
Journal: Circulation (2014)

Background: Multicellular self-assembling cardiospheres (CSps) exert regenerative and anti-fibrotic effects via paracrine mechanisms. CSp-derived cells are known to secrete exosomes which mediate most or all of the beneficial therapeutic effects. Objective: We evaluated the regenerative capacity of CSp-secreted exosomes in a model of chronic myocardial infarction (MI). We also determined whether CSp-exosomes could convert the phenotype of therapeutically-inert cells. Methods: Exosomes were isolated from CSp-conditioned media by adding a precipitation solution followed by centrifugation. One month post-MI, Wistar Kyoto rats (n=46) with permanent LAD ligation were injected intramyocardially with: a) human dermal fibroblasts (DFs), b) CSp exosomes, c) DFs primed with CSp-exosomes, d) CSps only or e) vehicle. Functional and histological analyses were performed 4 weeks after therapy. Mechanisms were also probed in vitro . Results: In vivo, CSp-exosomes and CSps equally increased ejection fraction (EF= 45±1% [CSp-exo], 44±2% [CSps], 33±1% [placebo] and 35±2% [DFs]) and reduced scar mass (48±8mg [CSp-exo], 45±4mg [CSps], 96±12mg [placebo] and 90±6mg [DFS]; both p&lt;0.01 by one way ANOVA). DFs that had been incubated with CSp-exosomes for 24 hours in culture conferred enhanced benefits compared to unprimed DFs (EF= 41±1% [primed-DFs]; p=0.05 vs unprimed DFs; scar mass= 49±5mg [primed-DFs]; p&lt;0.01 vs unprimed DFs). Confocal imaging revealed internalization of fluorescently-labeled CSp-exosomes in exosome-primed DFs. In vitro , exosome-primed DFs increased tube formation by HUVECs and inhibited cardiomyocyte apoptosis. Immunohistochemistry showed increased vessel density in all groups compared to vehicle or unprimed DFs. Conclusions: Administration of CSp-exosomes recapitulates the regenerative potential and functional benefits of CSps themselves. The surprising ability of CSp-exosomes to confer therapeutic efficacy on inert DFs may represent an unanticipated amplification mechanism for exosome-mediated benefits.
Vitamin Supplementation in Elderly Persons
Authors: Ranjit Kumar Chandra
Journal: JAMA (2003)

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
A single infusion of zoledronic acid 5 mg is significantly more effective than daily oral risedronate 5 mg in increasing bone mineral density of the lumbar spine, hip, femoral neck and trochanter in patients with glucocorticoid-induced osteoporosis
Authors: D. M. Reid, Jean-Pierre Devogelaer, K. Saag, Christian Roux, C. Lau, Jean-Yves Reginster, P. Papanastasiou, A. Ferreira, F. Hartl, T. Fashola, P. Mesenbrink, P. Sambrook
Journal: Annals of the Rheumatic Diseases (2008)
Prevalence of Toll-like receptor 2 and 4 polymorphisms in twins with inflammatory bowel disease : a population based Danish Swedish cohort study
Authors: Jonas Halfvarson, T. Jess, C. Jespersgaard, L. Riis, C. Tysk, G. Järnerot, P. Skytt Andersen, P. Munkholm
Journal: Gut (2005)

Prevalence of Toll-like receptor 2 and 4 polymorphisms in twins with inflammatory bowel disease : a population based Danish Swedish cohort study
Abstract 5574: Gli2 protein and the AR operational switch to the castration resistant prostate cancer transcription program
Authors: Na Li, Ralph Buttyan, Sarah Truong, Yue Yu, Mengqian Chen
Journal: Cancer Research (2014)

Abstract Gli proteins are transcription factors that mediate Hedgehog (HH) signaling in cells. Previously, we reported that Gli2 binds to the androgen receptor (AR) protein in prostate cancer (PCa) cells and further upregulates expression of genes under AR control. This “co-activator” effect allows the growth of Gli2 overexpressing LNCaP cells in androgen-depleted medium, mimicking the behavior of castrate resistant variants of PCa. We report here our success in localizing the specific binding domains between Gli2 and AR proteins. Outcomes of GST-pulldown and co-immunoprecipitation studies showed that Gli2 binds to AR via a limited domain (aa628-aa897) within the C-terminal region and this recognizes the tau5/AF5 domain (aa 392-558) within the N-terminal region of the AR protein. Because tau5/AF5 is conserved in truncated (splice variant) ARs, we also showed that Gli2 recognizes and co-activates the transcriptional activity of a truncated variant AR (AR-V7). To further define Gli2 regulatory functions on AR transcriptional activity in CRPC, we overexpressed Gli2ΔN (a constitutive-active form of Gli2) in LNCaP-AI (androgen-independent) cells and examined its effects on AR target gene expressions. Surprisingly, we found that Gli2Δ overexpression coincided with significant downregulated expression of genes considered “traditional” AR targets (i.e., KLK3 and KLK2), while increasing the expression of M-phase check-point genes, such as UBE2C, CDK1 and CDC20. In contrast, treatment of unmodified LNCaP-AI cells with the Gli-inhibitor, GANT61, significantly increased expression of KLK2 and KLK3 while downregulating UBE2C, CDC20 and CDK1. Our outcomes now imply that Gli2 differentially affects the AR transcriptional program in androgen-dependent (LNCaP) vs androgen-independent (LNCaP-AI) cells. In androgen-dependent cells, Gli2 co-activates expression of the traditional AR target genes while suppressing expression of genes involved in the CRPC transcriptional program whereas in androgen-independent cells, Gli2 co-activates expression of CRPC program genes while downregulating expression of traditional AR target genes. This dichotomy suggests that Gli2 participates in the decisions through which AR transcriptional activity is redirected in castration resistant disease. Supported by the DOD PCRP (W81XH-10-1-0493, to RB) Citation Format: Na Li, Ralph Buttyan, Sarah Truong, Yue Yu, Mengqian Chen. Gli2 protein and the AR operational switch to the castration resistant prostate cancer transcription program. [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 5574. doi:10.1158/1538-7445.AM2014-5574
Oxidative stress in rat lung after exposure to titanium dioxide and nickel oxide nanoparticles
Authors: Kazuaki Kawai, Yun-Shan Li, Yuya Kawasaki, Yasuo Morimoto
Journal: European Respiratory Journal (2014)

Oxidative stress is an intermediate step that leads to lung damage, and consequently to various disease states. Recently, considerable interest has been focused on the health effects of industrial nanomaterials, and several mechanisms underlying their adverse health effects have been proposed. Among them, oxidative stress is considered to be one of the most important. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) is a major type of oxidative DNA damage, and is often analyzed as a marker of oxidative stress in human and animal studies. The aim of this work was to examine whether oxidative DNA damage occurs in rat lungs exposed to titanium dioxide (TiO 2 ) and nickel oxide (NiO) nanoparticles. To detect oxidative DNA damage in the rat lung, the 8-OHdG levels in the lung DNA were analyzed by HPLC with electrochemical detection. As a result, the 8-OHdG levels in the lung DNA were significantly higher in the 1 mg TiO 2  nanoparticle intratracheal injection groups than the vehicle-injected control group, at 1 week after injection. In addition, the 8-OHdG level of the NiO nanoparticle injection group was significantly increased at 3 months after the 1 mg injection. Both effects were dose-dependent. These results indicated that the inhalation of TiO 2  and NiO nanoparticles might cause adverse health effects in the lung.
Original article: Eosinophil cationic protein (ECP) polymorphisms and association with asthma, s‐ECP levels and related phenotypes
Authors: M. C. Munthe‐Kaas, J. Gerritsen, K. H. Carlsen, D. Undlien, T. Egeland, B. Skinningsrud, T. Tørres, K. L. Carlsen
Journal: Allergy (2007)

Background: Eosinophil cationic protein (ECP) is a potent cytotoxic secretory protein with bactericidal and antiviral properties. ECP is released by activated eosinophils and regarded as a marker of eosinophilic inflammation. High levels of ECP have been reported in cases of active asthma and other allergic diseases. This study aimed to assess whether three single‐nucleotide polymorphisms (SNPs) in the ECP gene ( RNASE3 ) on chromosome 14 q24–q31 or their haplotypes are associated with asthma, allergy, or related phenotypes. Methods: The three SNPs −38CA, +371CG and +499CG in RNASE3 and their haplotypes were analyzed for associations with asthma, serum‐ECP (s‐ECP) levels, allergic sensitization (positive skin‐prick test to common allergens), bronchial hyperresponsiveness (BHR) assessed by methacholine inhalation, and serum‐IgE (s‐IgE) levels in 177 families from Norway and the Netherlands identified through siblings with asthma. Results: Transmission disequilibrium test (TDT) demonstrated significant associations between the A‐G‐G haplotype and asthma as well as the specific phenotypes allergic asthma (but not non‐allergic asthma), high s‐ECP, high s‐IgE and BHR, while the C‐G‐G haplotype was associated with reduced occurrence of these traits. In addition, the −38A allele was associated with high s‐ECP levels and allergic asthma. Conclusion: The present study suggests that the A‐G‐G haplotype in the RNASE3 gene influences the development of asthma, in particular, an allergic form of asthma. Furthermore, as the −38CA SNP lies in close vicinity of known intron‐regulatory sites, results of SNP analysis suggest that the detected association is possibly linked to a genetic transcriptional control of s‐ECP levels.
Long-Term Prognosis After Coronary Artery Calcification Testing in Asymptomatic Patients
Authors: Leslee J. Shaw, Ashley E. Giambrone, Michael J. Blaha, Joseph T. Knapper, Daniel S. Berman, Naveen Bellam, Arshed Quyyumi, Matthew J. Budoff, Tracy Q. Callister, James K. Min
Journal: Annals of Internal Medicine (2015)

Background: The extent of coronary artery calcification (CAC) and near-term adverse clinical outcomes are strongly related through 5 years of follow-up. Objective: To describe the ability of CAC scores to predict long-term mortality in persons without symptoms of coronary artery disease. Design: Observational cohort. Setting: Single-center, outpatient cardiology laboratory. Patients: 9715 asymptomatic patients. Measurements: Coronary artery calcification scoring and binary risk factor data were collected. The primary end point was time to all-cause mortality (median follow-up, 14.6 years). Univariable and multivariable Cox proportional hazards models were used to compare survival distributions. The net reclassification improvement statistic was calculated. Results: In Cox models adjusted for risk factors for coronary artery disease, the CAC score was highly predictive of all-cause mortality (P < 0.001). Overall 15-year mortality rates ranged from 3% to 28% for CAC scores from 0 to 1000 or greater (P < 0.001). The relative hazard for all-cause mortality ranged from 1.68 for a CAC score of 1 to 10 (P < 0.001) to 6.26 for a score of 1000 or greater (P < 0.001). The categorical net reclassification improvement using cut points of less than 7.5% to 22.5% or greater was 0.21 (95% CI, 0.16 to 0.32). Limitations: Data collection was limited to a single center with generalizability limitations. Only binary risk factor data were available, and CAC was only measured once. Conclusion: The extent of CAC accurately predicts 15-year mortality in a large cohort of asymptomatic patients. Long-term estimates of mortality provide a unique opportunity to examine the value of novel biomarkers, such as CAC, in estimating important patient outcomes. Primary Funding Source: None.
Anaerobic exercise decreases the progression of lung cancer in experimental mice
Authors: Renato Paceli, Rodrigo Cal, Carlos Santos, Anna Morais, Cassiano Neiva, Antonio Cordeiro, Kazuo Nagamine, Patricia Cury
Journal: European Respiratory Journal (2012)

Introduction: Lung cancer is one of the most incident neoplasms in the world representing the main cause of mortality for cancer. Studies have suggested evaluate the effectiveness of the use of the physical activity in the suppression, remission and reduction of the recurrence of tumors. Objective: To evaluate the effects of aerobic and anaerobic physical activity in the development and the progression of lung cancer. Material and methods: Lung tumors were induced with a dose of 3mg of Urethane/kg, in 67 male Balb - C type mice, divided in three groups: Group 1 - 24 mice treated with Urethane and without physical activity; Group 2 - 25 mice with Urethane and subjected to aerobic swimming free exercise; Group 3 - 18 mice with urethane, subjected to anaerobic swimming exercise with gradual loading 5 to 20% of body weight. All the animals were sacrificed after 20 weeks. Results: The median number of lesions (nodules and hyperplasia) was 3.0 for group 1, 2.0 for group 2 and 1.5 to 3 (p = 0.052). When compared only the presence or absence of lesion, there was a decrease in the number of lesions in group 3 compared with group 1 (p = 0.03) but not in relation to group 2. There were no metastases or other changes in other organs.

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Conclusions: In this study, the anaerobic physical activity but not aerobic, diminish the incidence of experimental lung tumors.

 [1]: pending:yes
Abstract 61: Associations of Cardiorespiratory and Musculoskeletal Fitness with Body Mass Index and Waist Circumference: Fitness versus Fatness in a Population-based Sample of Chilean 8th Graders
Authors: Michael D Garber, Felipe Lobelo, Marcelo Sajuria
Journal: Circulation (2014)

Background: In addition to excess adiposity, low cardiorespiratory fitness (CRF) and low musculoskeletal fitness (MSF) are important, independent risk factors for future cardio-metabolic disease in adolescents. To the best of our knowledge the fitness versus fatness relationship has not been studied in a population-based sample in Latin America. Hypothesis: We hypothesized that the physical fitness variables of CRF and MSF will be negatively associated with BMI and WC in an adolescent population in Chile, independent of potential confounders, but that a significant proportion of adolescents with poor body composition will exhibit healthy fitness levels. Methods: This cross-sectional study was based on a representative, single-stage, stratified cluster sample of 19,929 8th graders (median age = 14 years) in the 2011 National Education Survey from all regions of Chile. CRF was assessed with the 20 m shuttle run test, MSF with standing broad jump, and body composition with BMI and WC. CRF, MSF, BMI, and WC were classified according to health-related standards, validated against cardio-metabolic risk factors. Gender-stratified logistic regression models for both CRF and MSF included socioeconomic status, age, region, the other fitness variable, BMI, and WC. Analyses were weighted and considered complex sample design. Results: In both genders, the adjusted prevalence of high-risk CRF was higher among students with high-risk BMI (boys: prevalence ratio (PR) = 1.88; girls: PR = 1.71; both p&lt;0.05) and with high-risk WC (boys: PR = 1.77; girls: PR = 1.21; both p&lt;0.05), compared with their healthy counterparts. BMI but not WC was an independent correlate of high-risk MSF in girls (PR = 1.32; p&lt;0.05). Both BMI (PR=1.64; p&lt;0.05) and WC (PR=1.11; p&lt;0.05) were independent correlates of high-risk MSF in boys. A substantial proportion of students with poor body composition had healthy fitness, and vice versa: 46% of boys and 25% of girls with high-risk BMI had healthy CRF. Conversely, 35% of boys and 55% of girls with high-risk CRF had a healthy BMI. Similarly, 47% of boys and 51% of girls with high-risk BMI had healthy MSF whereas 43% of boys and girls with high-risk MSF had a healthy BMI. Conclusions: In this large representative sample of Chilean adolescents, BMI and WC were inversely correlated with CRF and MSF. Nonetheless, the sizeable proportion of adolescents with poor body composition but healthy fitness, and vice versa, underscores the importance of assessing both CRF and MSF for a more complete representation of adolescent cardio-metabolic risk.
Familial Risk of Sjögren's Syndrome and Co‐aggregation of Autoimmune Diseases in Affected Families: A Nationwide Population Study
Authors: Chang‐Fu Kuo, Matthew J. Grainge, Ana M. Valdes, Lai‐Chu See, Shue‐Fen Luo, Kuang‐Hui Yu, Weiya Zhang, Michael Doherty
Journal: Arthritis & Rheumatology (2015)

Objective To investigate familial aggregation of Sjögren's syndrome (SS) and the relative risks (RRs) of other autoimmune disease in relatives of patients with SS. Methods We identified 23,658,577 beneficiaries enrolled in the Taiwan National Health Insurance system in 2010, of whom 12,754 had SS. We identified 21,009,551 parent–child relationships and 17,168,340 pairs of full siblings. The familial risks of SS and other autoimmune diseases, tetrachoric correlation, and familial transmission were estimated. Results We identified 105 patients with SS who had an affected first‐degree relative. The RR of SS was 18.99 (95% confidence interval [95% CI] 9.76–36.93) in siblings of patients with SS, 11.31 (95% CI 8.34–15.33) in offspring, and 12.46 (95% CI 9.34–16.62) in parents. Tetrachoric correlation coefficients were 0.53 (95% CI 0.41–0.65) for cotwins of affected individuals and 0.21 (95% CI 0.16–0.26) for full siblings. The familial transmission (heritability plus shared environmental contribution) was 0.54 (95% CI 0.44–0.77). In first‐degree relatives of patients with SS, the RRs were 2.95 (95% CI 2.33–3.73) for rheumatoid arthritis, 6.25 (95% CI 5.15–7.58) for systemic lupus erythematosus, 2.39 (95% CI 0.77–7.41) for systemic sclerosis, 0.71 (95% CI 0.10–5.07) for idiopathic inflammatory myopathy, 1.97 (95% CI 1.29–3.02) for type 1 diabetes mellitus, 3.38 (95% CI 1.26–9.05) for multiple sclerosis, 1.67 (95% CI 0.83–3.33) for myasthenia gravis, 1.25 (95% CI 1.04–1.50) for psoriasis, 1.21 (95% CI 0.39–3.76) for inflammatory bowel disease, and 2.29 (95% CI 1.19–4.40) for vasculitis. Conclusion The risk of SS and other autoimmune diseases is increased in relatives of patients with SS, and more than one‐half of phenotypic variance in SS can be explained by familial factors.
Abstract 12358: Achievement of 85% of Maximal Age Predicted Heart Rate Is Not an Appropriate Exercise Stress End Point and May Result in Underestimation of Inducible ECG Ischemia
Authors: Mohit Jain, Ben A Lin, Alerice Walker, Frans J Wackers
Journal: Circulation (2010)

There is a strong relationship between maximal exercise capacity (duration and METs) and cardiac outcomes. These parameters play a key role in the evaluation of patients with suspected coronary art...
Effort Launched to Study Stem Cell Lines, Train Researchers How to Nurture Them
Authors: Brian Vastag
Journal: JAMA (2003)

BETHESDA, MD—A year and a half after President Bush announced his decision topermit federal fundingforsomehuman embryonic stem cell research, the National Institutes of Health (NIH) has disbursed$25million touniversities and launchedanon-campuseffort todescribe and standardize various cell lineages. An NIH stem cell registry now lists nine lines of “distribution quality” cells available to researchers: five from ES Cell International, Brisbane, Australia; two from WiCell Research Institute, Madison, Wis; one from BresaGen Inc, Atlanta, Ga; and one from the University of California, San Francisco. Such cell lines have been tested for specific markers and shown to grow into somatic cells in vitro.