tbuckley/cabot-search huggingface dataset:
TNF alpha promotes coxsackie and adenovirus receptor (CAR) phosphorylation by PKC delta to drive leukocyte transepithelial migration
Authors: Alexander Hicks, Penny Morton, Alistair Noble, Emma Rayner, Maddy Parsons, George Santis
Journal: European Respiratory Journal (2014)

CAR has been established as the primary docking receptor for members of the coxsackie B virus and adenovirus family. More recently, it has been shown that CAR plays an important role in the maintenance of tight junctions and in trans-epithelial migration of leukocytes. These functions have important implications in the immune responses of the respiratory tract, through maintenance of the epithelial barrier function and modulating leucocyte exposure to pathogens. Using epithelial cell lines with mutated versions of the CAR cytoplasmic tail this study has demonstrated that phosphorylation of the cytoplasmic component of CAR promoted transmigration of leukocytes across an epithelial layer. Furthermore, using imaging and western techniques, it was shown that this phosphorylation was triggered by TNF-alpha during inflammation. Using knockdown techniques and chemical inhibition a mechanistic pathway for this phosphorylation effect has been identified. It was shown to occur via stimulation of the enzyme PI-3-K leading to activation and phosphorylation of a PKC delta-dependent pathway. This process was also found to only occur when CAR was homo-dimerised at tight junctions. These events are not confined to immortalised cell lines and have also been demonstrated to be relevant in-vivo. The cytoplasmic tail of CAR was shown to be phosphorylated at cell junctions between epithelial cells of the small airways in both acute (TNF driven) and chronic (ovalbumin driven) inflammatory mouse models. This work identifies a novel mechanism by which the cytoplasmic tail of CAR is involved in the immune response of the respiratory epithelium.
Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse
Authors: Muhammad Faiyaz ul Haque, Lily M. King, Deborah Krakow, Rita M. Cantor, Michael E. Rusiniak, Richard T. Swank, Andrea Superti-Furga, Sayedul Haque, Hasan Abbas, Wasim Ahmad, Mahmud Ahmad, Daniel H. Cohn
Journal: Nature Genetics (1998)
Abstract P040: Animal and Vegetable Protein Intake and Coronary Artery Calcium - The Kangbuk Samsung Health Study
Authors: Yuni Choi, Seungho Ryu, Yoosoo Chang, Jung Eun Lee, Eunju Sung, Juhee Cho, Sanjay Rampal, Di Zhao, Yiyi Zhang, Jiin Ahn, Miguel Cainzos-Achirica, Roberto Pastor-Barriuso, Joao A Lima, Hocheol Shin, Eliseo Guallar
Journal: Circulation (2015)

Introduction: Few studies have evaluated the association between type and amount of dietary protein intake and clinically evident cardiovascular disease, with inconsistent findings, and no study has investigated the association between type and amount of dietary protein intake and subclinical coronary atherosclerosis. Hypothesis: We examined the associations of total, animal, and vegetable protein intakes with coronary artery calcium (CAC) in a large population of asymptomatic adults. Methods: We performed a cross-sectional study of 29,034 asymptomatic young and middle-aged adults (mean age 41.6 years; males 80.3%) who are free of clinically evident cancer or cardiovascular disease. All participants underwent a health screening examination including cardiac computed tomography for CAC scoring and completed a food frequency questionnaire at the Kangbuk Samsung Hospital Total Healthcare Centers in Seoul and Suwon, South Korea from March, 2011 to April, 2013. Protein intake and other nutrient intake were adjusted for total energy intake using the residual method. Multivariable-adjusted CAC score ratios and 95% confidence intervals (CIs) were estimated by robust Tobit regression models for natural logarithm (CAC score + 1). Results: The proportion of study participants with detectable CAC (CAC score &gt; 0) was 13.4 %. After adjustment for total energy intake, other nutrient intake, and potential confounding factors, we found an increased prevalence of CAC with higher animal protein intake, but not with total and vegetable protein intakes. In multivariable-adjusted models, CAC ratios (95% CIs) comparing the highest with the lowest quintiles were 1.82 (1.09-3.04; P for trend = 0.01) for animal protein intake, 1.25 (0.87-1.81; P for trend = 0.13) for vegetable protein intake, and 1.19 (0.74-1.93; P for trend = 0.59) for total protein intake. Conclusion: High animal protein intake, but not total or vegetable protein, was associated with an increased prevalence of subclinical coronary atherosclerosis and with a greater degree of coronary calcification.
Abstract 11500: J-Point Syndromes From the Vectorcardiogram Point of View
Authors: Carlos A Pastore, Nelson Samesima, Horácio G Pereira
Journal: Circulation (2014)

Introduction: The potentially fatal outcome related to J-point syndromes raises heated debate about the pathophysiology of Brugada syndrome (BrS) and early repolarization (ER). It has not been established yet if they carry a depolarization, a repolarization or both electrical problems. Hypothesis: The objective of this study was to define BrS and ER characteristic and distinctive electrical patterns, using aspects of the QRS complex loops, ST-segments and T-waves obtained from the classical vectorcardiogram (VCG). Methods: VCG loops of 29 BrS patients and 30 individuals with ER were analyzed qualitatively and quantitatively. Non-paired t-test and ROC curve statistics were used (p≤ 0.05 significance level). Results: Mean age: 47±15 vs 38±14y.o. (p=0.02), 66% vs 90% male (p=0.03); QRS duration: 102±10 vs 95±13ms (p=0.03), BrS vs ER, respectively. All QRS loops showed an end-conduction delay located in right posterior-anterior quadrant (BrS) or left posterior-anterior quadrant (ER). A “break” in the QRS loop end, very much resembling a “nose”, is seen in BrS (100%), while in ER the QRS loop “break” was smoother with a “fish-hook” shape (100%). Normal T-wave loops with counterclockwise rotation were present in 86.2% of BrS and 73.3% of ER. End-conduction delay of 34±6ms vs 22±5ms (p&lt;0.0001); J-point amplitude of 0.14±0.07mV vs 0.22±0.08mV (p&lt;0.0001); SÂJ-point of 103±19° vs 55±16° (p&lt;0.0001), BrS vs ER, respectively. A 75o cutoff value (ROC analysis) could diagnose BrS (96.6% sensitivity, 93.3% specificity). Conclusions: The vectorcardiogram could clearly differentiate BrS from ER qualitatively as well as quantitatively: the transverse plane of VCG shows in BrS cases a longer end-conduction delay (&gt;30ms), with a right-sided and posterior-anteriorly oriented loop, with the aspect of a “nose”; in ER cases the end-conduction delay is shorter, located at the left posterior-anterior quadrant, with the aspect of a “fish-hook”. With a J-point angle above 75o we could diagnose BrS with 96.6% sensitivity and 93.3% specificity.
Cerivastatin, a Hydroxymethylglutaryl Coenzyme A Reductase Inhibitor, Improves Endothelial Function in Elderly Diabetic Patients Within 3 Days
Authors: Masayoshi Hashimoto, Hozuka Akita
Journal: Circulation (2002)

In the July 24, 2001, issue of Circulation, Tsunekawa et al 1 found that 3 days of statin therapy resulted in significant improvement of endothelial function, independent of lipidlowering, in a study population of elderly patients with diabetes mellitus.The study provides new insight into statins' direct effect on endothelial function over such a short period of time.However, we have some questions concerning flow-mediated dilatation (%FMD) and nitroglycerin-induced dilatation (%NTG).Noninvasive techniques for examining endotheliumdependent and endothelium-independent vasodilatation using sonography have been widely applied in human studies since their first publication. 2Endothelium-dependent dilatation, which is measured as %FMD, is thought to be caused by smooth muscle relaxation secondary to nitric oxide production and/or release from endothelial cells.Nitroglycerin administration is thought to provide nitric oxide exogenously.It is not known whether the amount of nitric oxide provided by sublingual administration of nitroglycerin is greater than that provided by flow stimuli.However, endothelium-independent vasodilatation caused by nitroglycerin is usually greater than %FMD.Using this method, we have been examining human subjects.The total number of %FMD examinations exceeded 800 subjects, 520 of whom agreed to undergo measurement of %NTG together with %FMD.The coefficient of variation for measurements of %FMD was 5.84Ϯ0.25%and for %NTG was 3.97Ϯ0.24%,as we reported previously. 3The coefficient of variation for reproducibility of this ultrasound determination of %FMD was 9.77Ϯ0.82%and that of NTG was 7.24Ϯ0.49%.Because detection of subtle changes is critical to this method, reproducibility should be determined.The mean %FMD/%NTG was 0.39, and its standard deviation was 0.26.Only 5 subjects (less than 1%) showed %FMD/%NTG greater than 1.These 5 subjects were patients with atherosclerotic disease who required routine nitroglycerin administration.%NTG tends to decrease according to age, which was discussed in the paper.However, it is difficult to believe that %FMD exceeded %NTG, which was observed after 3 days and after 3 months of statin therapy.We question the mechanism underlying this phenomenon.
Surgical Diseases of the Gall-Bladder, Liver and Pancreas and Their Treatment.
Authors: Moses Behrend
Journal: JAMA (1928)

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
287. Enhancement of Therapeutic Efficacy of G207 for the Treatment of Malignant Glioma through Musashi1 Promotor Retargeting of ICP 34.5 Gene-Mediated Virulence
Authors: Takahito Yazaki, Ryuichi Kanai, Hideyuki Tomita, Atsuo Shinoda, Hideyuki Okano, Takeshi Kawase
Journal: Molecular Therapy (2004)

Top of pageAbstract
G207 is a conditionally replicating derivative of herpes simplex virus type1 (HSV-1) engineered with deletions of both ICP34.5 loci and a lacZ insertion disabling the ICP6 gene. G207 exhibits an efficient oncolytic activity in vitro and in vivo studies, yet minimal toxicity in normal tissue, and is now in clinical trial for malignant glioma. Accoding to the results of clinical trial, however, though G207 has been proved to be safe, the efficacy was not so impressive. Deletion of theICP34.5 gene coding for virulence made G207 extremely safe, but it markedly reduced cytotoxicity mediated by HSV type1. To enhance the therapeutic efficacy of G207 without deminishing its safety, we reintroduced ICP34.5 gene into G207 in the form of defective virus (dvM345) under transcriptional control of musashi1 promotor (P/musashi1). Musashi1, an evolutionarily conserved neural RNA-binding protein, has recently been shown to be expressed in human malignant gliomas and be used as a marker for them. Its promotor, P/musashi1 was functional selectively in human glioma cell lines (U87MG, U251, T98G) in this study and dvM345 showed much higher therapeutic efficacy both in culture and in vivo glioma model, compared to G207 alone, without diminishing a favorable toxicity profile. These results suggest that transcriptional regulation of ICP34.5 by P/musashi1 can be used to target HSV-1 virulence toward gliomas while maintaining the desirable neuroattenuated phenotype of G207.
66. A safe and efficient lentiviral vector system: optimisation of virus production and purification
Authors: Donald S. Anson
Journal: Molecular Therapy (2004)

Top of pageAbstract
We have previously described 5 and 6 plasmid systems for production of recombinant, HIV-1 derived, lentiviral vectors (Fuller and Anson, 20011. These systems utilise codon-optimised reading frames for expression of Gag/GagPol. We have now further developed these systems by constructing more efficient expression constructs, and by utilising codon-optimized reading frames for all HIV-1 proteins (with the exception of Env, the virus being pseudotyped with VSV-G). In addition, we have refined the design of our vector construct to increase the synthesis of genomic transcripts. By careful titration of plasmid ratios and absolute amounts, and by careful optimization of the conditions for transfection of 293T cells and for virus collection, we have increased the titre of virus that can be produced with the 5-plasmid system over 8-fold. We can now routinely produce virus using the 5-plasmid system with a titre of >5 × 107 A549 transducing units per ml. Vectors using a liver specific (alpha-1-antitrypsin gene) promoter, and two different ubiquitous (phosphoglycerate kinase gene and myeloproliferative sarcoma virus long terminal repeat) promoters, for transgene expression have been constructed. All three vectors are available with either the enhanced yellow fluorescent protein or LacZ marker genes.

To further increase the safety of our vector system we have manipulated the codon usage in the GagPol expression (helper) construct to minimize homology with the HIV-1 gag gene sequence that is present in our vector constructs. We show that this results in a significant decrease in the transfer of gagpol gene sequences to transduced cells without reducing the efficiency of virus production.

Large-scale production of virus was facilitated by using a serum free medium (OptiPro-SFM, Invitrogen) for virus collection which allowed rapid and efficient processing of viral supernatant using a combination of ultrafiltration and ultracentrifugation. OptiPro-SFM was superior to a number of other serum free media that were tested. The use of coated cell culture vessels, sodium butyrate, or BES in place of HeBS for calcium phosphate coprecipitation, did not improve viral titres.

In conclusion, we now have an extremely safe and efficient recombinant HIV-1 vector system available with a choice of marker genes and internal promoters.
Classification of Psychiatric Disorders
Authors: Robert A Jenders
Journal: JAMA (2005)

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 4954: Risk Factors for Death or Transplant in Chronic Symptomatic Heart Failure in Children: Subanalysis of Pediatric Carvedilol Study
Authors: Elizabeth D Blume, Mark M Boucek, Daphne Hsu, Bernie LaSalle, Kimberlee Gauvreau, Robert E Shaddy
Journal: Circulation (2008)

The Pediatric Carvedilol Study trial offers a unique opportunity to investigate patient characteristics and risk factors associated with death or transplant in a population of children with moderate heart failure symptoms. The database from the Pediatric Carvedilol Study trial includes 157 children enrolled with symptomatic heart failure (NYHA II–IV) and ejection fraction (EF)&lt;40%. For this analysis, the patients were divided into by outcome into 2 groups: those who died or underwent heart transplant during the study period (D/HTx) and those who did not (non-D/HTx). Baseline variables were compared using standard parametric and non-parametric testing. Multivariate analysis was performed using logistic regression Results: Of the 157 children, the median age at enrollment was 3 yrs (0.2–17.8yrs). Fifty-two percent were male, and 116/157 (74%) had a left ventricle (LV) as the systemic ventricle. All pts except 3 were NYHA/Ross class II-III, with a median EF of 25.7%, median BNP of 111, and median LVEDD z-score of 6.04. Overall incidence of D/HTx in the enrolled patients over the study period was 30/157 (19%), with 12 deaths and 18 transplants. Risk factors for D/HTx were older age (8.1yrs vs 2.1 yrs, p&lt; 0.006), higher BNP levels at enrollment (250 vs 80, p&lt;0.003) and worse AVV regurgitation (p&lt;0.012), but not diagnosis of congenital heart disease, ventricular morphology, or qualitative assessment of systemic ventricular dysfunction. In the subgroup of patients with a systemic LV, the D/HTx group had a significantly larger EDD z-score (7.7 vs 5.8, p=0.05), but no difference in ejection fraction (25.9 vs 25.6, p=0.8) compared to the non D/HTx. In a multi-variate model after adjusting for age, LV EDD z-score and BNP at enrollment were significantly related to risk for D/HTx. For this pediatric population with chronic symptomatic heart failure, risk factors for death or transplant included older age, higher BNP, and AVVR. In the subgroup of patients with a systemic left ventricle, larger LV EDD z-score, but not lower EF, was significantly related to short term risk for death or transplant.
Vitamin E Supplementation in Healthy Persons—Reply
Authors: Garret A. FitzGerald
Journal: JAMA (2001)

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
Serum YKL-40 level is associated with apnea hypopnea index in patients with obstructive sleep apnea syndrome
Authors: Levent Cem Mutlu, Feti Tülübas, Recep Alp, Gizem Kaplan, Zeynep Deniz Mut, Ahmet Gürel
Journal: European Respiratory Journal (2014)

Introduction  Obstructive sleep apnea syndrome (OSAS) has been associated with elevations in biochemical markers of inflammation. Although the exact mechanism is not known, both sleep deprivation and hypoxemia are believed to be important causative factors. YKL-40, also known as chitinase-like protein was shown to be related with various inflammatory conditions including atherosclerosis, diabetes, cancer and asthma.  The aim of the study was to evaluate the relationship between YKL-40 levels and apnea hypopnea index in patients with obstructive sleep apnea syndrome.  Methods:  The study was conducted in the sleep unit of Namik Kemal University research center. From January 2013 to December 2013, 120 patients diagnosed with OSAS by polisomnography and 40 age, sex, and body mass index (BMI) matched subjects, with AHI   The OSAS patients were further divided into mild, moderate and severe groups based on AHI. Serum YKL-40 concentrations were measured by Enzyme-Linked Immuno Sorbent Assay (ELISA).  Results  YKL-40 levels were signifiacantly elevated in OSAS patients than control group, Serum YKL-40 levels were found 97,3 ± 19,09 pg/ml in control group, 124,11± 47,97 pg/ml in mild,:169;39 ± 9,42 pg/ml in moderate and 174;78±77,46pg/ml in severe group. Spearman correlation analysis showed that serum YKL-40 levels were significantly and positively correlated with AHI (r = 0,434, p  Conclusion  The study demonstrated that high serum YKL-40 levels were correlated to severity of OSAS and could be a biomarker for predicting and progression of the disease.
Implantable Cardioverter-Defibrillator Use Among Medicare Patients With Low Ejection Fraction After Acute Myocardial Infarction
Authors: Sean D. Pokorney, Amy L. Miller, Anita Y. Chen, Laine Thomas, Gregg C. Fonarow, James A. de Lemos, Sana M. Al-Khatib, Eric D. Peterson, Tracy Y. Wang
Journal: JAMA (2015)

Implantable cardioverter-defibrillators (ICDs) are not recommended within 40 days of myocardial infarction (MI); thus, ICD implantation might not be considered during the post-MI care transition.To examine ICD implantation rates and associated mortality among older MI patients with low ejection fraction (EF).Retrospective observational study of Medicare beneficiaries with an EF of 35% or less after MI, treated at 441 US hospitals between 2007 and 2010, excluding patients with prior ICD implantation. Follow-up data were available through December 2010.ICD implantation within 1 year of MI vs no ICD implantation within 1 year of MI.Patient characteristics associated with receiving an ICD within 1 year after discharge and 2-year mortality associated with ICD implantation.Among 10,318 MI patients with EF of 35%or lower, the cumulative 1-year ICD implantation rate was 8.1% (95%CI, 7.6%-8.7%). Patients with ICD implantation were more likely to have prior coronary artery bypass graft procedures, higher peak troponin levels, in-hospital cardiogenic shock, and cardiology follow-up within 2 weeks after discharge relative to patients who did not receive an ICD within 1 year. Implantation of ICD was associated with lower 2-year mortality (15.3 events per 100 patient-years [128 deaths in 838 patient-years] vs 26.4 events per 100 patient-years [3033 deaths in 11 479 patient-years]; adjusted HR, 0.64; 95%CI, 0.53-0.78). [table: see text]In this large registry study of older patients who experienced MI from 2007-2010, fewer than 1 in 10 eligible patients with low EF received an ICD within 1 year after MI, although ICD implantation was associated with lower risk-adjusted mortality at 2 years. Additional research is needed to determine evidence-based approaches to increase ICD implantation among eligible patients.