tbuckley/cabot-search huggingface dataset:
Human case of swine influenza A (H1N1), Aragon, Spain, November 2008
Authors: B Adiego Sancho, M Omeñaca Terés, S Martínez Cuenca, P Rodrigo Val, P Sánchez Villanueva, I Casas, F Pozo, P Pérez Breña
Journal: Eurosurveillance (2009)

A human case of swine influenza A (H1N1) in a 50-year-old woman from a village near Teruel (Aragon, in the north-east of Spain), with a population of about 200 inhabitants, has been reported in November 2008.
Abstract 12185: Restoration of Autophagy in Endothelial Cells From Patients With Diabetes Improves Nitric Oxide Signaling
Authors: Jessica L Fetterman, Nir Flint, Monica Holbrook, Erika A Linder, Brittany D Berk, Mai A Duess, Bihua Feng, Melissa G Farb, Noyan Gokce, Orian S Shirihai, Naomi M Hamburg, Joseph A Vita
Journal: Circulation (2014)

Diabetes is associated with oxidative stress and decreased nitric oxide bioactivity in the vasculature. Autophagy is a critical multistep pathway that eliminates damaged proteins and organelles from the cell. Emerging evidence suggests impaired autophagy in non-vascular tissues contributes to the pathogenesis of diabetes. We hypothesized that impaired autophagy contributes to endothelial dysfunction associated with diabetes in humans. We measured vascular function and autophagy markers in freshly isolated endothelial cells (ECs) from patients with diabetes and non-diabetic controls. Diabetes was associated with endothelial dysfunction characterized by lower brachial artery flow-mediated dilation and impaired activation of eNOS by insulin in ECs. ECs from diabetic patients had higher levels of p62 (Figure), a protein that accumulates with reduced autophagic flux. Measures of autophagy initiation including rapamycin stimulation, beclin 1 levels, and LC3 puncta were not different. Global activation of autophagy with spermidine reversed endothelial dysfunction in freshly isolated ECs from diabetic patients (Figure). In ECs from controls, inhibiting autophagy with bafilomycin impaired eNOS activation confirming that intact autophagy promotes NO signaling. Evidence from cultured endothelial cells in high glucose conditions suggested that lysosomal function is intact as measured by lysosomal number and acidification. Blocking the terminal step of autophagy with bafilomycin in ECs from diabetics led to a further accumulation of p62, suggesting intact but insufficient levels of autophagy. Lamp2a, which facilitates the merger of autophagosomes and lysosomes, was higher in diabetic cells, possibly reflecting a compensatory response to reduced flux. These findings provide evidence for inadequate autophagic flux in ECs from diabetic patients that contributes to impaired NO signaling and may be a target for therapy of diabetic vascular disease.
Abstract 2415: Long-Term Baroreflex Activation Therapy Increases the Threshold for the Induction of Lethal Ventricular Arrhythmias in Dogs with Chronic Advanced Heart Failure
Authors: Mengjun Wang, Valerio Zaca, Alice Jiang, Itamar Ilsar, Matthew Ebinger, Michael B Sabbah, Kattlin Dye, Claudio Schuger, Hani N Sabbah
Journal: Circulation (2008)

Heart failure (HF) is associated with a high incidence of ventricular tachycardia (VT) and fibrillation (VF). Patients with HF in whom these lethal arrhythmias can be induced by electrophysiological (EP) testing carry a high risk of sudden cardiac death. We showed that chronic electrical carotid baroreflex activation therapy (BAT) with the Rheos® System (CVRx, Inc.) improves LV function, attenuates LV remodeling and restores autonomic sympathetic-parasympathetic balance in dogs with HF. This study examined the effects of long-term therapy with BAT on the induction of VT or VF in dogs with coronary microembolization-induced HF (LV ejection fraction ~20%). Eleven dogs with HF underwent EP testing at baseline prior to therapy and after 3 and 6 months of therapy with BAT and again 6 weeks after withdrawal of BAT therapy (n = 7) or no therapy at all (Control, n = 4). Programmed ventricular stimulation was performed from the right ventricular apex and included delivery of up to 4 extrastimuli at progressively shorter coupling intervals (in steps of 10 msec). The extrastimuli were delivered following 8 ventricular paced beats with a drive cycle length between 600 and 200 msec. If a sustained monomorphic VT or VF could not be induced, isoproterenol infusion was initiated to increase the sinus rate by ~30% and the EP stimulation protocol was repeated. At baseline, a sustained VT or VF was induced in all 11 dogs (100%). After 3 and 6 months of follow-up, all Control dogs (100%) were induced into sustained VT or VF. After 3 months of BAT, only 3 of 7 dogs (43%) were induced into sustained VT or VF. After 6 months of BAT, only 2 of 7 dogs (29%) were induced into sustained VT or VF. Finally after withdrawal of BAT therapy, all dogs (100%) were again induced into systained VT or VF. In addition to improving LV function and attenuating LV remodeling, long-term monotherapy with BAT markedly increases the threshold for lethal ventricular arrhythmias in dogs with chronic HF. This is a marked improvement over inducibility of lethal arrhythmias seen in historical untreated controls. This benefit of BAT supports the continued exploration of this device as a therapeutic modality for treating patients with chronic HF and increased risk of sudden cardiac death.
Dual B Cell Immunotherapy Is Superior to Individual Anti‐CD20 Depletion or BAFF Blockade in Murine Models of Spontaneous or Accelerated Lupus
Authors: WeiYu Lin, Dhaya Seshasayee, Wyne P. Lee, Patrick Caplazi, Sami McVay, Eric Suto, Allen Nguyen, Zhonghua Lin, Yonglian Sun, Laura DeForge, Mercedesz Balazs, Flavius Martin, Ali A. Zarrin
Journal: Arthritis & Rheumatology (2014)

To determine whether a combination of B cell depletion and BAFF blockade is more effective than monotherapy in treating models of spontaneous or accelerated systemic lupus erythematosus (SLE) in (NZB × NZW)F1 mice.Clinical parameters such as disease progression-free survival, proteinuria, and renal injury were assessed in models of spontaneous, interferon-α (IFNα)-accelerated, or pristane-accelerated lupus in (NZB × NZW)F1 mice. Treatment arms included anti-CD20 (B cell depletion), B lymphocyte stimulator receptor 3 fusion protein (BR-3-Fc) (BAFF blockade), the combination of anti-CD20 and BR-3-Fc, isotype control, or cyclophosphamide. In models of spontaneous, IFNα-accelerated, or pristane-accelerated lupus, mice were treated for 24 weeks, 8 weeks, or 12 weeks, respectively. Peripheral and resident B cell subsets and various autoantibodies were examined.Compared to B cell depletion or BAFF blockade alone, combined therapy significantly improved disease manifestations in all 3 lupus models. In addition, marginal zone B cells, plasmablasts, and circulating and tissue plasma cells were decreased more effectively. Dual B cell immunotherapy also reduced multiple classes of pathogenic autoantibodies, consistent with its observed effectiveness in reducing immune complex-mediated renal injury.Dual immunotherapy via B cell depletion and BAFF blockade is more efficacious than single agent immunotherapy in murine SLE models, and this combination treatment is predicted to be an effective strategy for immunotherapy in human SLE.
Imaging to Diagnose Cardiovascular Disease
Authors: Mike Mitka
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
Comment on Khunti et al. Hypoglycemia and Risk of Cardiovascular Disease and All-Cause Mortality in Insulin-Treated People With Type 1 and Type 2 Diabetes: A Cohort Study. Diabetes Care 2015;38:316–322
Authors: Marga Giménez, Antonio J. Amor, Carmen Quirós, Ignacio Conget
Journal: Diabetes Care (2015)

We have read the article by Khunti et al. (1) suggesting that hypoglycemia is associated with an increased risk of cardiovascular (CV) events and all-cause mortality in insulin-treated patients with diabetes.

The authors mentioned in the discussion that several potential mechanisms linking hypoglycemia and CV risk have been proposed. However, in their opinion, these mechanisms are more likely to explain a transient increase in CV risk during the acute episode of hypoglycemia rather than the longer-term relationship observed in their current study.

We addressed the question of whether repeated episodes of hypoglycemia represent an aggravating factor for macrovascular disease in subjects with type 1 diabetes (T1D) in a …
Generation and Evaluation of a New Replication-Competent Retrovirus (RCR) Vector Coding for the SuperCD Suicide Gene
Authors: Kai Hauschulz, Stefan Seefried, Andrea Schenk, Irina Smirnow, Wolfgang Wybranietz, Noriyuki Kasahara, Michael Bitzer, Ulrich M. Lauer
Journal: Molecular Therapy (2004)

Limited efficiency of in vivo gene transfer constitutes the main problem in cancer gene therapy applications employing replication-defective retroviral (RDR) vectors based on Moloney murine leukaemia virus (MoMLV). Therefore, replication-competent retroviral (RCR) vectors have been developed being able to transmit inserted transgenes very efficiently not only in cell culture, but also throughout entire tumor tissues. For efficient elimination of transduced tumor cells RCRs encoding well-known suicide genes like herpes simplex virus thymidine kinase (HSV TK) or yeast cytosine deaminase (YCD) have been made. Here, we generated a new RCR carrying the highly effective SuperCD gene which is composed of a bifunctional fusion suicide gene of YCD and yeast uracil phosphoribosyltransferase (YUPRT). We then compared the in vitro killing potential of this viral vector with the parental one (coding for YCD only). Viral vectors were produced by transient transfection of 293T producer cells with plasmids containing the proviral DNA. Viral supernatant was harvested and titered using real-time-PCR. Human hepatoma cells were transduced with each vector with equal multiplicity of infections; subsequently, incubation with the prodrug 5-FC was carried out. We observed enhanced cell cytotoxicity for the new RCR-SuperCD vector compared to parental RCR-YCD vector. Our results demonstrate that RCR-SuperCD vectors are more effective in toxifying the 5-FC prodrug.
Abstract P320: Discordance of Framingham Risk Score and Reynolds Risk Score to Global Vascular Risk Score: Results from the Hispanic Community Health Study/Study of Latinos
Authors: Molly Jung, Hector M Medina, Martha Daviglus, Marina DelRios, Mario Garcia, Hector M González, Robert C Kaplan, Ileana L Pina, Paul Sorlie, Daniela Sotres-Alvarez, Clinton B Wright
Journal: Circulation (2014)

Introduction: The Framingham Risk Score (FRS) is a coronary heart disease (CHD) risk model established using an ethnically homogeneous population that predicts 10-year hard CHD events, myocardial infarction (MI) and coronary death. The Reynolds Risk Score (RRS) and Global Vascular Risk Score (GVRS) are validated CHD risk models that, in addition to hard CHD events, predict stroke and other CHD outcomes. In addition to major CHD risk factors, RRS adds systemic inflammation and family history of MI as GVRS adds behavioral and anthropometric measures. This study aims to compare agreement of RRS and GVRS with FRS among Hispanic/Latino adults and to describe discordance in RRS and GVRS with FRS categories, by socio-demographic characteristics. Methods: HCHS/SOL is a population-based cohort study of Hispanics/Latinos in four US communities. The analytic sample includes 6,058 non-diabetic participants 45-74 years of age with no past history of CHD and stroke who underwent comprehensive baseline examination. 10-year hard CHD risk score was calculated; participants were categorized as low (&lt;10%), moderate (10-&lt;20%), and high (≥20%) risk. Kappa scores were calculated to compare agreement of RRS and GVRS with FRS. Socio-demographic characteristics of concordance and discordance were characterized overall; multinomial logistic regression models was used to examine age-sex-adjusted likelihood of in discordance by these factors. Results: Mean age of the participants was 55 (SE=0.15) years, 54.3% were women, 41% had family history of CHD, and 90% were foreign born. Overall, 4,805 (74%) had low FRS, 1,143 (24%) had moderate FRS, and 110 (2%) had high FRS. There was poor agreement between RRS and FRS (Kappa=0.16, P&lt;0.01) and fair agreement between GVRS and FRS (Kappa=0.36, P&lt;0.01). In age-sex-adjusted analyses, RRS and GVRS were both more likely to classify persons of moderate and high risk who are between the ages of 60-74; GVRS classified more moderate and high risk women than the FRS. RRS and GVRS discordance with FRS was not associated with nativity and length of time in US. Conclusion: Significant discordance was observed between RRS and GVRS compared to FRS. Among Hispanic/Latino adults, use of RRS or GVRS may be more inclusive in classifying older age adults and women at high 10-year CHD risk.
Abstract 2609: The role of focal adhesion kinase (FAK), PI3K/AKT and p53/mouse double minute 2 homologue (MDM2) complex in the pathobiology of Merlin-deficient tumors
Authors: Clemens O. Hanemann, Sylwia Ammoun, Marei C. Schmid, Lu Zhou
Journal: Cancer Research (2014)

Abstract Deficiency of the tumor suppressor merlin leads to the development of schwannomas, meningiomas and ependymomas occurring spontaneously or as a part of a hereditary disease Neurofibromatosis type 2 (NF2). Another tumor suppressor/transcription factor p53 regulates proliferation, survival and differentiation. P53 deficiency/inactivation correlates with tumor development and can be negatively regulated by FAK, PI3K/AKT and MDM2 and possibly positively by merlin and JNK in different models. The function of p53 in merlin deficient tumors is not known. Using our in vitro model of primary human schwannoma cells we demonstrated that FAK is overexpressed/activated and localises to the nucleus in schwannoma cells leading to increased proliferation. AKT is strongly activated via PDGF- and IGF-I- receptors increasing survival. Here we investigated p53 regulation and its role in proliferation and survival of human primary schwannoma cells. p53 is downregulated and MDM2 upregulated in human schwannoma cells leading to increased proliferation and survival. p53 is regulated by merlin involving JNK FAK, AKT and MDM2. Thus merlin potentiates p53 activity and when using Nutlin-3 this increases p53 stability and total levels of p53 in schwannoma cells decreasing proliferation and survival. These findings are important to dissect mechanisms responsible for development of merlin-deficient tumors and identification of therapeutic targets. Citation Format: Clemens O. Hanemann, Sylwia Ammoun, Marei C. Schmid, Lu Zhou. The role of focal adhesion kinase (FAK), PI3K/AKT and p53/mouse double minute 2 homologue (MDM2) complex in the pathobiology of Merlin-deficient tumors. [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 2609. doi:10.1158/1538-7445.AM2014-2609
All advanced stage non-Hodgkin's lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment
Authors: JG Gribben, As Freedman, SD Woo, K Blake, RS Shu, G Freeman, JA Longtine, GS Pinkus, LM Nadler
Journal: Blood (1991)
Letter by Morris et al Regarding Article, “Improved Quality of Life After 1 Year With an Invasive Versus a Noninvasive Treatment Strategy in Claudicants: One-Year Results of the Invasive Revascularization or Not in Intermittent Claudication (IRONIC) Trial”
Authors: Dylan R. Morris, Joseph V. Moxon, Jonathan Golledge
Journal: Circulation (2015)
Abstract 15517: Receipt of Special Education Services Among Children with Congenital Heart Defects in Atlanta, Georgia
Authors: Tiffany Colarusso, Autry Andrew, Hilda Razzaghi, Coleen Boyle, William Mahle, Kim Van Naarden Braun, Adolfo Correa
Journal: Circulation (2014)

BACKGROUND: Population-based information on special education service needs among children with congenital heart defects (CHDs) is limited. We investigated the prevalence of receipt of special education services among children with CHDs. METHODS: Children born from 1982-2004 in metropolitan Atlanta with CHDs (n=3,744) were identified from a population-based birth defect surveillance program, and contemporaneous children born without major birth defects (n=860,715) were identified from birth certificates. Cohorts were linked to special education files for 1992-2012 school years to identify receipt of special education services. Children with CHDs and non-cardiac defects or genetic syndromes were excluded; children with isolated CHDs were classified by presence or absence of critical CHDs (i.e., defects needing intervention in the first year of life). We evaluated prevalence of special education services and calculated prevalence ratios (PRs) using children without birth defects as reference. RESULTS: Children with CHDs were 50% more likely than those without birth defects to use special education services (PR 1.5; 95% Confidence interval 1.4-1.7). Similar to children without birth defects, the most common eligibility among children with CHDs was speech/language impairment. Compared to children without birth defects, the prevalence of several special education eligibilities were significantly higher among children with all CHDs: any intellectual disability (PR 3.8), sensory impairment (PR 3.0), other health impairment (PR 2.8), significant developmental delay (PR 1.9), orthopedic impairment (PR 1.9), and specific learning disability (PR 1.4). For most special education eligibilities, there was no significant variation in the elevated prevalence ratios by presence or absence of critical CHDs. CONCLUSIONS: Children with many types of CHDs received special education services more often than children without birth defects. These findings highlight important resource needs for children with CHDs. Furthermore, they suggest that recommendations to perform developmental screening only on children with select CHDs may miss or delay identification of children with other CHDs, who may also need special education services.
141. Development of a One-Step Column Purification of Minicircle Vector DNA Devoid of Bacterial Sequences That Results in High Level Persistent Transgene Expression In Vivo
Authors: Zhi-Ying Chen, Cheng-Yi He, Mark A. Kay
Journal: Molecular Therapy (2004)

We have shown that episomal circular DNA vectors free of plasmid bacterial DNA sequences are capable of indefinite high level transgene expression in vivo. The minicircle vector is generated in bacteria from a parental plasmid containing an inducible phiC31 integrase gene, and att P and att B recognition sites flanking the therapeutic expression cassette. Recombination results in the formation of two circular DNA molecules, one containing the plasmid bacterial backbone and the other the eukaryotic expression cassette. Previously, the minicircle was purified away from the plasmid bacterial DNA by cesium chloride banding in an ultracentrifuge (Chen et al., Mol Ther. 8:495, 2003). We have now devised a one-step purification method that results in a high yield of minicircle vector. To do this, two copies of the phiC31 integrase gene under the control of an inducible promoter (BAD), together with the transgene expression cassette flanked by the attB and attP sites, were built into a minicircle-producing plasmid, p2phiC31. An intron encoded restriction enzyme I-Sce I gene, also under the control of the BAD promoter, together with an I-Sce I restriction site, were also built into p2phiC31. Top 10 E. coli was used to amplify p2phiC31 using standard plasmid preparation. To induce the phiC31 integrase-mediated minicircle formation, an over night culture was re-suspended 4 to 1 (vol/vol) in fresh LB broth containing the pBAD inducer 1% L-arabinose and incubated at 32°C with constant shaking for one hour. The temperature of the incubation was increased to 37°C, to optimize I-Sce I enzymatic activity, for an additional 2 hours. Linearization of the plasmid bacterial DNA circle by the restriction enzyme resulted in its rapid degradation by exonucleases in bacteria. The mini-circle expression cassette becomes the only episomal circular DNA and is easily isolated by an affinity purification column. Using this technology to prepare a minicircle encoding a 4 kb human factor IX expression cassette, > 1 mg of minicircle of 97 percent purity can be prepared from 1 liter of over night bacterial growth. When injected into the livers of animals by hydrodynamic infusion, about 10 μg/ml of serum hFIX was expressed for up to 7 weeks (length of study). The high yield, simple purification, and robust and persistence of transgene expression makes these vectors viable for in vivo gene therapy applications.
Everything You Ever Wanted to Know About Evidence-based Medicine
Authors: Rebecca Voelker
Journal: JAMA (2015)

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