tbuckley/cabot-search huggingface dataset:
Abstract 16531: Decreased Cardiovascular Events in Familial Hypercholesterolemic Patients Treated With Mipomersen, an Antisense Inhibitor of Apolipoprotein B Translation
Authors: Bart Duell, Raul D Santos, Mary P McGowan, Asif Mahmood, Brenda F Baker, Richard S Geary, Walter Singleton, John J Kastelein
Journal: Circulation (2014)

Background: Familial hypercholesterolemia (FH) is associated with a 10-20 fold increase in cardiovascular (CV) events. Mipomersen has been shown to significantly lower levels of atherogenic lipoproteins in plasma. Previous safety analysis of all patients in phase 3 trials found no meaningful imbalance in CV events between placebo and mipomersen arms. Hypothesis: Treatment with mipomersen for at least 1 year will reduce CV events in FH patients taking maximally tolerated lipid-lowering therapy. Methods: Rates of major adverse CV events (MACE) during 2 years prior to mipomersen treatment were compared to MACE after treatment in 104 FH patients who participated in one of three phase 3 blinded randomized placebo-controlled 6-month trials and an open-label extension study (NCT00607373, NCT00706849, NCT00794664, NCT00694109). One third of patients (n=34) received placebo for the initial 6 months followed by mipomersen for at least 1 year. Two thirds (n=70) received blinded mipomersen for 6 months followed by at...
A simple model based on mutation and selection explains trends in codon and amino-acid usage and GC composition within and across genomes
Authors: Robin D Knight, Stephen J Freeland, Laura F Landweber
Journal: Genome biology (2001)

Correlations between genome composition (in terms of GC content) and usage of particular codons and amino acids have been widely reported, but poorly explained. We show here that a simple model of processes acting at the nucleotide level explains codon usage across a large sample of species (311 bacteria, 28 archaea and 257 eukaryotes). The model quantitatively predicts responses (slope and intercept of the regression line on genome GC content) of individual codons and amino acids to genome composition.Codons respond to genome composition on the basis of their GC content relative to their synonyms (explaining 71-87% of the variance in response among the different codons, depending on measure). Amino-acid responses are determined by the mean GC content of their codons (explaining 71-79% of the variance). Similar trends hold for genes within a genome. Position-dependent selection for error minimization explains why individual bases respond differently to directional mutation pressure.Our model suggests that GC content drives codon usage (rather than the converse). It unifies a large body of empirical evidence concerning relationships between GC content and amino-acid or codon usage in disparate systems. The relationship between GC content and codon and amino-acid usage is ahistorical; it is replicated independently in the three domains of living organisms, reinforcing the idea that genes and genomes at mutation/selection equilibrium reproduce a unique relationship between nucleic acid and protein composition. Thus, the model may be useful in predicting amino-acid or nucleotide sequences in poorly characterized taxa.
US alarmed over rise in tuberculosis among immigrants
Authors: Fred Charatan
Journal: BMJ (2000)

With tuberculosis surging in developing countries and immigration to the United States from those countries at a record high, public health officials are alarmed at the rising incidence of pulmonary tuberculosis among immigrants.

In 1998, immigrants, who accounted for only 10% of the population, accounted for nearly 42% of the 18 371 cases of tuberculosis reported throughout the United States.

The Centers for Disease Control and Prevention said that from 1986 to 1997 the number of tuberculosis cases among people born outside the United States …
Abstract 17004: Cardiogenic Shock Complicating Non-ST-Elevation Myocardial Infarction: Temporal Trends in the United States, 2003-2011
Authors: Dhaval Kolte, Sahil Khera, Kathir S Subramanian, Chandrasekar Palaniswamy, Marjan Mujib, Wilbert S Aronow, Robert Timmermans, Diwakar Jain, Sachin Sule, Ali Ahmed, William H Frishman, Howard A Cooper, Deepak L Bhatt, Gregg C Fonarow, Julio A Panza
Journal: Circulation (2014)

Background:  Limited data are available on the contemporary and potentially changing trends in the incidence and outcomes of cardiogenic shock complicating non-ST-elevation myocardial infarction (NSTEMI).   Objectives:  To examine temporal trends in the incidence of cardiogenic shock in patients with NSTEMI, as well as trends in coronary angiography, revascularization (PCI or CABG), and outcomes (in-hospital mortality and length of stay) in these patients.   Methods:  We used the 2003-2011 Nationwide Inpatient Sample databases to identify all patients ≥18 years of age with a primary diagnosis of NSTEMI (ICD-9-CM code 410.71). Patients with a concomitant diagnosis of cardiogenic shock were identified using ICD-9-CM code 785.51. Temporal trends in incidence of cardiogenic shock, coronary angiography and revascularization rates, and outcomes were analyzed using logistic regression.   Results:  From 2003 to 2011, among 3,628,071 patients with NSTEMI, 85,176 (2.3%) had cardiogenic shock. The proportion of NSTEMI patients who had cardiogenic shock documented increased from 1.8% in 2003 to 3.1% in 2011 (p trend  trend  trend  8 days remained unchanged over the study period.   Conclusion:  We observed an increasing incidence of cardiogenic shock in patients with NSTEMI together with an increase in coronary angiography and revascularization rates in these patients. Risk-adjusted in-hospital mortality decreased, and length of stay remained unchanged during the study period.
The relationship between community resources and state hospital recidivism
Authors: W H Fisher, J L Geller, F Altaffer, M B Bennett
Journal: American Journal of Psychiatry (1992)

The authors examined the propositions that a revolving state hospital door is an inevitable consequence of deinstitutionalization and that enhancing resources for community-based care can limit this phenomenon.They analyzed the recidivism patterns of state hospital patients in a region of Massachusetts where, because of a federal court consent decree, the level of funding for community programs was more than twice as high as it was in other regions in the state and compared the pattern of recidivism in this region with that observed in the other areas of the state.Despite the fact that the average daily state hospital census in the resource-rich region was only half that of the other regions, longitudinal data on hospital use showed that the readmission patterns were similar in all state regions.The authors suggest that attributes of serious and persistent mental illness may have more effect on hospital readmission patterns than service system variables.
Précis de microscopie: Technique, expérimentation, diagnostic
Authors: Maurice Langeron
Journal: JAMA (1934)

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
Folate Distribution in Cultured Human Cells
Authors: David S. Rosenblatt, Bernard A. Cooper, Sally Lue-Shing, Paul W. K. Wong, Stanley Berlow, Kuniaka Narisawa, Regula Baumgartner
Journal: Journal of Clinical Investigation (1979)

We have studied the distribution of folate coenzyme forms in cultured human fibroblasts from control lines and from lines derived from nine patients representing all of the published reports of 5,10-CH(2)-H(4)PteGlu reductase deficiency. Based on mobility on DEAE-Sephadex and differential microbiological assay the major folate fractions in extracts of human fibroblasts were 5-CH(3)-H(4)PteGlu, 10-CHO-H(4)PteGlu, and 5-CHO-H(4)PteGlu with smaller fractions, which included 5-CH(3)-H(2)PteGlu, 10-CHO-PteGlu, and H(4)PteGlu. Evidence that the 5-CHO-H(4)PteGlu may have been derived from 5,10-CH=H(4)PteGlu during extraction is presented. In most of the mutant fibroblasts the absolute concentration of 5-CH(3)-H(4)PteGlu was lower than in control cells but the proportion of intracellular folate which was 5-CH(3)-H(4)PteGlu was strikingly lower in mutant cells when determined by chromatography or differential microbiological assay. In both control and mutant cells most of the 5-CH(3)-H(4)-PteGlu was polyglutamate. The proportion of intracellular folate which was polyglutamate was similar in control and mutant cells. A direct relationship was observed between the proportion of cellular folate which was 5-CH(3)-H(4)PteGlu, and both the clinical severity of this disorder and the residual enzyme activity indicating that the distribution of different folates may be an important control of intracellular folate metabolism. These studies indicate that 5,10-CH(2)-H(4)PteGlu reductase is the only significant intracellular pathway for the generation of 5-CH(3)-H(4)PteGlu, that the activity of this enzyme regulates the level of this folate in control and mutant cells under conditions of culture used here, that the majority of intracellular folate is in the polyglutamate form, and that the relative distribution of folates may control folate metabolism by interaction in the various folate reactions.
New TB Strategy
Authors: Joan Stephenson
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Medicaid at 50: Time for a Major Overhaul
Authors: Stuart M. Butler
Journal: JAMA (2015)

JAMA: What has the Center for Medicare and Medicaid Innovation (CMMI) accomplished in the past few years? DR BERWICK: [T]he center has really stimulated I think an unprecedented amount of activity around the country in the localities, very local activities, to come up with new ways to give and support care. A great example has been the Partnership for Patients. That was a program that I established when I was administrator, a $1 billion investment in reducing unnecessary readmissions to hospitals and in preventing so-called hospital-acquired conditions. These are injuries in hospital care like bedsores and central-line infections and medication errors. The interim results of the partnership were just reported a couple of months ago, and they’re quite stunning. We have doubledigit improvements—reductions in complications in hospitals, readmission rates the lowest they have been on record, I think... and a lot of progress in the nation on patient safety, and that’s just one contribution of CMMI. It also has fostered experiments with new payment systems like the pioneer accountable care organizations, like the big bundle-payment experiment that is showing some pretty good results, so I think it’s been a very, very wise investment in reinventing care.
225. Phenotypic Correction of ALD Mouse after Hematopoietic Cell Transplantation and Evaluation of Hematopoietic Stem Cell Gene Therapy with a Lentivirus Vector
Authors: Sonia Benhamida, Françoise Fouquet, Ann Moser, Patrick Aubourg, Nathalie Cartier
Journal: Molecular Therapy (2004)

X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder (1 in 17.000) characterized by progressive demyelination of the central nervous system, adrenal insufficiency and abnormal accumulation of very-long-chain fatty acids (VLCFA) in plasma and tissues, including the brain and spinal cord white matter.
Cigarette smoke alters the expression of the pro-inflammatory LTB4 receptor and increases the neutrophil adhesion in bronchial epithelial cells
Authors: Elisabetta Pace, Maria Ferraro, Antonino Giarratano, Serafina Sciarrino, Mark Gjomarkaj
Journal: European Respiratory Journal (2011)

LTB4 is importantly involved in the inflammatory responses of chronic obstructive pulmonary disease (COPD). In COPD an increased expression of LTB4 receptors, BLT1 and of PPAR-a, was observed. Since LTB4 is reduced upon TLR4 mutation and since cigarette smoke extracts (CSE) increase the expression of TLR4 in bronchial epithelial cells, the aims of this study were to explore whether CSE with/without LPS (a ligand of TLR4) or mini-BAL supernatants from smokers alter, in bronchial epithelial cells, the expression (evaluated by flow-cytometry analysis) of pro (BLT2) and anti-inflammatory (PPAR-a) LTB4 receptors. Moreover, we evaluated the effects of CSE on the expression of ICAM-1 (by flow-cytometry analysis), on the binding of STAT-1 to ICAM-1 promoter (by ChiP analysis), and on the adhesiveness of bronchial epithelial cells to neutrophils (by fluorimetry).

CSE alone increased BLT2 while decreased PPARa expression. The addition of LPS did not modify CSE effects. mini-BAL from smokers increased BLT2 but not PPARa expression. A neutralizing TLR4 antibody reduced the expression of BLT2 but it had no effects in PPAR-a expression. CSE increased the binding of STAT-1 to ICAM-1 promoter and increased the expression of ICAM-1 in bronchial epithelial cells. CSE and mini-BAL from smokers increased the adhesiveness of bronchial epithelial cells toward neutrophils more than mini-BAL from non-smokers. These findings suggest that, in bronchial epithelial cells, CSE promote a prevalent induction of pro-inflammatory BLT2 receptors and activate mechanisms leading to increase neutrophil adhesion, a mechanism contributing to airway neutrophilia.
607. In Vitro and In Vivo Monitoring of 5-Fluorosytosine Metabolism with 19F-NMR Spectroscopy after Adenoviral Transduction of Cells with Bifunctional Yeast CDUPRT Fusion Gene
Authors: Vera Simonenko, Huandong Pageant, Du Fei, Thian C. Ng
Journal: Molecular Therapy (2004)

Transfer into tumor of  genes is an attractive gene therapy strategy for selective elimination of cancer cells. One of the newly invented suicide gene encodes bifunctional yeast CDUPRT fusion protein, which combines the enzymatic activity of cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT). This protein efficiently catalyzes the direct conversion of 5-FC (a non-toxic prodrug) into the toxic metabolites 5-fluorouracil (5-FU) and its toxic derivative 5-fluorouridine-5'-monophosphate (FUMP). This study was undertaken to evaluate the applicability of 19F-MRS for monitoring in vitro and in vivo of the conversion of 5-fluorocytosine (5-FC) to fluorouracil after adenovirus mediated transfer of a CDUPRT Fusion Gene. For this purpose a replication incompetent adenoviral vector carrying a cytomegalovirus (CMV)-driven transcription unit of the yeast CDUPRT gene in E1 region was constructed. We employed both 19F-MRS and cell biology techniques to measure the pharmacokinetics and cytotoxicity of 5-FC for infected human glioma D54MG cells.
Abstract 13230: Convergence of CXCL12 and PHACTR1: Novel Genome Wide Signals for Myocardial Infarction Regulate Plasma CXCL12 Levels
Authors: Nehal N Mehta, Dilusha William, Mingyao Li, Amit Khera, Liming Qu, Stephanie DerOhannessian, Leticia Pruscino, Lalarukh Shaikh, Christine Hinkle, Jing He, Ioannis Stylianou, Hakon Hakonarson, Daniel J Rader, Muredach P Reilly
Journal: Circulation (2010)

Background: Recent genome wide association studies have shown association between coronary artery disease (CAD) / myocardial infarction (MI) and common variation at locus 10q11 (8.1x10-9) downstrea...
Abstract 1947: Plasticity of CD44+ colorectal cancer stem cells depends on TGF-beta-induced epithelial mesenchymal transition(EMT): Evidences from an ex vivo culture
Authors: Michitaka Nakano, Hiroshi Ariyama, Shingo Tamura, Taichi Isobe, Kohta Miyawaki, Yuta Okumura, Hitoshi Kusaba, Eishi Baba, Koichi Akashi
Journal: Cancer Research (2014)

Abstract Background EpCAMhigh CD44+ colorectal cancer (CRC) cells are thought to be cancer stem cells. Recently CD44- CRC cells are also suggested to gain a character of cancer stem cells, but the molecular mechanisms have not been clarified. Epithelial-mesenchymal transition (EMT), which is observed in several caner cell lines, could be a possible process of cancer cells to obtain stemness. However, whether primary human CRC cells underwent EMT has not been proven. Patients and Methods We obtained surgical specimens of 30 cases of advanced CRC, and cultured isolated primary cancer cells in matrigel-based medium containing several growth factors. For induction of EMT, TGF-beta was added into the culture of CD44+ and CD44- cells. Immunocytochemistry staining and flow cytometry of the spheroid cells and single cell PCR analysis of the cultured cells using 48-gene set that included EMT-related genes (BioMark HD System:Fluidigm Corporation) were performed. Results Cancer cells grew spherically (50 μm&amp;gt; diameter) in 20 out of 30 samples after a week culture of whole isolated cancer cells. The sphere mostly consisted of CD44+ cells, and non-sphere forming single cells were CD44-negative. Isolated CD44+ cells from primary samples gave rise to CD44+ and CD44- cells in a week culture. Interestingly, 10% of CD44- cell from primary samples also expressed CD44. Similar to the previous findings of cell lines that TGF-beta-induced EMT could convert CD44- cells into CD44+ cancer initiating cells, increased number of CD44+ cells appeared from primary CD44- cells cultured with TGF-beta. In this culture, N-cadherin+ cells increased time-dependent manner and most of this N-cadherin expressing cells co-expressed CD44. In single cell PCR analysis, increased expression of EMT-related genes, vimentin and TWIST1, were preferentially detected in CD44+N-Cadherin+ cells. Conclusions To our knowledge, this is the first report that CD44- cells from primary samples undergo EMT and convert into CD44+ cells by TGF-β treatment. Investigation whether these CD44+ converted cells have cancer stem cell properties such as tumorigenic potential in immunodeficient mouse, self renewing ability and drug resistance is underway. Citation Format: Michitaka Nakano, Hiroshi Ariyama, Shingo Tamura, Taichi Isobe, Kohta Miyawaki, Yuta Okumura, Hitoshi Kusaba, Eishi Baba, Koichi Akashi. Plasticity of CD44+ colorectal cancer stem cells depends on TGF-beta-induced epithelial mesenchymal transition(EMT): Evidences from an ex vivo culture. [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 1947. doi:10.1158/1538-7445.AM2014-1947
Hematopoietic Malignancies Demonstrate Loss-of-Function Mutations ofBAX
Authors: Jules P.P. Meijerink, Ewald J.B.M. Mensink, Kun Wang, Thomas W. Sedlak, Annet W. Slöetjes, Theo de Witte, Gabriel Waksman, Stanley J. Korsmeyer
Journal: Blood (1998)
Platelet-Activating Factor Mediates MMP-2 expression and Activation via Phosphorylation of CREB and Contributes to Melanoma Metastasis
Authors: Vladislava O. Melnikova, Alexandra A. Mourad-Zeidan, Dina Chelouche Lev, Menashe Bar-Eli
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4377 

Overexpression of cAMP-responsive element (CRE)-binding protein (CREB) and activating transcription factor 1 (ATF-1) contributes to melanoma progression and metastasis at least in part by promoting tumor cell survival and stimulating matrix metalloproteinase 2 (MMP-2) expression. However, little is known about the regulation of CREB and ATF-1 activities and their phosphorylation within the tumor microenvironment. We analyzed the effect of platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, for its ability to activate CREB and ATF-1 in eight cultured human melanoma cell lines and found that PAF receptor (PAFR) was expressed in all eight lines. In metastatic melanoma cell lines, PAF induced CREB and ATF-1 phosphorylation via a PAFR-mediated signal transduction mechanism that required Pertussis toxin-insensitive Gαq protein and adenylate cyclase activity and was antagonized by a protein kinase A and p38 MAP kinase inhibitors. Addition of PAF to metastatic A375SM cells stimulated CRE-dependent transcription, as observed in a luciferase reporter assay, without increasing the CRE DNA-binding capacity of CREB. Furthermore, PAF stimulated the gelatinase activity of MMP-2 by activating transcription and MMP-2 expression. MMP-2 activation correlated with the PAF-induced increase in the expression of an MMP-2 activator, membrane type 1 MMP. PAF-induced expression of pro-MMP-2 was causally related to PAF-induced CREB and ATF-1 phosphorylation: it was prevented by PAFR antagonist and inhibitors of p38 MAPK and PKA and was abrogated upon quenching of CREB and ATF-1 activities by forced overexpression of a dominant-negative form of CREB. PAF-induced MMP-2 activation was also downregulated by p38 MAPK and PKA inhibitors. Finally, PAFR antagonist PCA4248 inhibited the development of A375SM lung metastasis in nude mice. This result indicated that PAF acts as a promoter of melanoma metastasis in vivo . We propose that metastatic melanoma cells overexpressing CREB/ATF-1 are better equipped than non-metastatic cells to respond to PAF within the tumor microenvironment.