tbuckley/cabot-search huggingface dataset:
High prevalence of osteoporotic vertebral fractures in patients with Crohn's disease
Authors: J Klaus
Journal: Gut (2002)

Osteopenia and osteoporosis are frequent in Crohn's disease. However, there are few data on related vertebral fractures. Therefore, we evaluated prospectively the prevalence of osteoporotic vertebral fractures in these patients.A total of 293 patients were screened with dual energy x ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur. In 156 patients with lumbar osteopenia or osteoporosis (T score <-1), x ray examinations of the thoracic and lumbar spine were performed. Assessment of fractures included visual reading of x rays and quantitative morphometry of the vertebral bodies (T4-L4), analogous to the criteria of the European Vertebral Osteoporosis Study.In 34 (21.8%; 18 female) of 156 Crohn's disease patients with reduced bone mineral density, 63 osteoporotic vertebral fractures (50 fx. (osteoporotic fracture with visible fracture line running into the vertebral body and/or change of outer shape) and 13 fxd. (osteoporotic fracture with change of outer shape but without visible fracture line)) were found, 50 fx. in 25 (16%, 15 female) patients and 13 fxd. in nine (5.8%, three female) patients. In four patients the fractures were clinically evident and associated with severe back pain. Approximately one third of patients with fractures were younger than 30 years. Lumbar bone mineral density was significantly reduced in patients with fractures compared with those without (T score -2.50 (0.88) v -2.07 (0.66); p<0.025) but not at the hip (-2.0 (1.1) v -1.81 (0.87); p=0.38). In subgroups analyses, no significant differences were observed.In patients with Crohn's disease and reduced bone mineral density, the prevalence of vertebral fractures-that is, manifest osteoporosis-was strikingly high at 22%, even in those aged less than 30 years, a problem deserving further clinical attention.
Motexafin Gadolinium Disrupts Zinc Metabolism in Human Cancer Cell Lines
Authors: Darren Magda, Philip Lecane, Richard A. Miller, Cheryl Lepp, Dale Miles, Mimi Mesfin, John E. Biaglow, Vincent V. Ho, Danny Chawannakul, Shailender Nagpal, Mazen W. Karaman, Joseph G. Hacia
Journal: Cancer Research (2005)

To gain a better understanding of the mechanism of action of the metal cation-containing chemotherapeutic drug motexafin gadolinium (MGd), gene expression profiling analyses were conducted on plateau phase human lung cancer (A549) cell cultures treated with MGd. Drug treatment elicited a highly specific response that manifested in elevated levels of metallothionein isoform and zinc transporter 1 (ZnT1) transcripts. A549 cultures incubated with MGd in the presence of exogenous zinc acetate displayed synergistic increases in the levels of intracellular free zinc, metallothionein transcripts, inhibition of thioredoxin reductase activity, and cell death. Similar effects were observed in PC3 prostate cancer and Ramos B-cell lymphoma cell lines. Intracellular free zinc levels increased in response to treatment with MGd in the absence of exogenous zinc, indicating that MGd can mobilize bound intracellular zinc. These findings lead us to suggest that an important component of the anticancer activity of MGd is related to its ability to disrupt zinc metabolism and alter cellular availability of zinc. This class of compounds may provide insight into the development of novel cancer drugs targeting control of intracellular free zinc and the roles that zinc and other metal cations play in biochemical pathways relevant to cancer.
A CLEC16A variant confers risk for juvenile idiopathic arthritis and anti-cyclic citrullinated peptide antibody negative rheumatoid arthritis
Authors: B. Skinningsrud, B. A. Lie, E. S. Husebye, T. K. Kvien, O. Forre, B. Flato, A. Stormyr, G. Joner, P. R. Njolstad, T. Egeland, D. E. Undlien
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective</h3> Variants in CLEC16A have conferred susceptibility to autoimmune diseases in genome-wide association studies. The present work aimed to investigate the locus9 involvements in juvenile idiopathic arthritis (JIA) and further explore the association with rheumatoid arthritis (RA), type 1 diabetes (T1D) and Addison9s disease (AD) in the Norwegian population. <h3>Methods</h3> Three single nucleotide polymorphisms (SNPs) were genotyped in patients with RA (n=809), JIA (n=509), T1D (n=1211) and AD (n=414) and in healthy controls (n=2149). <h3>Results</h3> All diseases were associated with CLEC16A, but with different SNPs. The intron 22 SNP, rs6498169, was associated with RA (p=0.006) and JIA (p=0.016) and the intron 19 SNPs, rs12708716/rs12917716, with T1D (p=1×10−5) and AD (p=2×10−4). The RA association was confined to the anti-cyclic citrullinated peptide antibody (anti-CCP) negative subgroup (p=2×10−4). <h3>Conclusion</h3> This is the first report of a CLEC16A association with JIA and a split of the RA association according to anti-CCP status. Different causative variants underlie the rheumatic versus the organ specific diseases.
SPECIFICITY OF RECOMBINATION OF H AND L CHAINS FROM HUMAN γG-MYELOMA PROTEINS
Authors: Howard M. Grey, Mart Mannik
Journal: The Journal of Experimental Medicine (1965)

Dissociated H and L chains of human gammaG-myeloma proteins were recombined by removal of conditions interrupting non-covalent interactions. In the process of recombination 7S molecules were formed. It was demonstrated that the H chains from individual gammaG-myeloma proteins recombine with their own L chains but also with L chains derived from other myeloma proteins. In some instances, however, the L chains from other myeloma proteins did not recombine as avidly with the H chains as the autologous L chains. The specificity of the non-covalent interactions of H and L chains was particularly well brought out by competitive recombination experiments where an individual H chain had a choice of recombining with its own L chain or with the L chain obtained from another myeloma protein. In this manner a spectrum of affinities between individual H chains and several L chains was demonstrated. In the vast majority of recombinations there was a clearcut preference for recombination to take place between the H and L chains derived from the same protein. It is postulated that this specificity is related to differences in the primary structure, which cause differences in configuration of these homogeneous H and L chains and that these configurations then dictate on thermodynamic grounds the pairing of H chains with particular L chains.
Comparison of a Polymer-Based Paclitaxel-Eluting Stent With a Bare Metal Stent in Patients With Complex Coronary Artery Disease
Authors: Gregg W. Stone, Stephen G. Ellis, Louis Cannon, J. Tift Mann, Joel D. Greenberg, Douglas Spriggs, Charles D. O'Shaughnessy, Samuel DeMaio, Patrick Hall, Jeffrey J. Popma, Joerg Koglin, Mary E. Russell, for the TAXUS V Investigators
Journal: JAMA (2005)

Compared with bare metal stents, drug-eluting stents reduce restenosis in noncomplex lesions. The utility of drug-eluting stents has not been evaluated in more difficult stenoses.To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in a patient population with more complex lesions than previously studied.Prospective, placebo-controlled, double-blind, multicenter randomized trial conducted from February 2003 to March 2004 at 66 academic and community-based institutions with 1156 patients who underwent stent implantation in a single coronary artery stenosis (vessel diameter, 2.25-4.0 mm; lesion length, 10-46 mm), including 664 patients (57.4%) with complex or previously unstudied lesions (requiring 2.25-mm, 4.0-mm, and/or multiple stents) and 9-month clinical and angiographic follow-up.Patients were randomly assigned to receive 1 or more bare metal stents (n = 579) or identical-appearing paclitaxel-eluting stents (n = 577).Ischemia-driven target vessel revascularization at 9 months.Baseline characteristics were well matched. Diabetes was present in 31% of patients. The mean (SD) reference vessel diameter was 2.69 (0.57) mm, the reference lesion length was 17.2 (9.2) mm, and 78% of lesions were type B2/C. A mean (SD) of 1.38 (0.58) stents (total mean [SD] length, 28.4 [13.1] mm) were implanted per lesion; 33% of lesions required multiple stents. Stents that were 2.25 mm and 4.0 mm in diameter were used in 18% and 17% of lesions, respectively. Compared with bare metal stents, paclitaxel-eluting stents reduced the 9-month rate of target lesion revascularization from 15.7% to 8.6% (P<.001) and target vessel revascularization from 17.3% to 12.1% (P = .02). Similar rates were observed for cardiac death or myocardial infarction (5.5% for bare metal stent group vs 5.7% for paclitaxel-eluting stent group) and stent thrombosis (0.7% in both groups). Angiographic restenosis was reduced from 33.9% to 18.9% in the entire study cohort (P<.001), including among patients receiving 2.25-mm stents (49.4% vs 31.2%; P = .01), 4.0-mm stents (14.4% vs 3.5%; P = .02), and multiple stents (57.8% vs 27.2%; P<.001).Compared with a bare metal stent, implantation of the paclitaxel-eluting stent in a patient population with complex lesions effectively reduces clinical and angiographic restenosis.
Psychoactive Medications and Risk of Delirium in Hospitalized Cancer Patients
Authors: Jean-David Gaudreau, Pierre Gagnon, François Harel, Marc-André Roy, Annie Tremblay
Journal: Journal of Clinical Oncology (2005)

Psychoactive medications are biologically plausible and potentially modifiable risk factors of delirium. To date, however, research findings are inconsistent regarding their association with delirium. The association between exposure to anticholinergics, benzodiazepines, corticosteroids, and opioids and the risk of delirium was studied.A total of 261 hospitalized cancer patients were followed up with repeated assessments by using the Nursing Delirium Screening Scale for up to 4 weeks for incident delirium. Detailed exposure to psychoactive medications was documented daily. Strengths of association with delirium were expressed as hazard ratios (HRs) in univariate and multivariate analyses by using Cox regression models. All medication variables were coded as time-dependent covariates. Whenever possible, exposure was computed by using cumulative daily doses in equivalents; dichotomous cutoffs were determined.During follow-up (mean, 8.6 days), 43 patients became delirious (16.5%). Delirium was associated with a history of delirium and the presence of hepatic metastases at admission. Analysis of the effect of medications was performed adjusting for these factors. Patients exposed to daily doses of benzodiazepines above 2 mg (HR, 2.04; 95% CI, 1.05 to 3.97), above 15 mg of corticosteroids (HR, 2.67; 95% CI, 1.18 to 6.03), or above 90 mg of opioids (HR, 2.12; 95% CI, 1.09 to 4.13) had increases in the risks for delirium. We did not observe associations between anticholinergics and risk for delirium.Exposure to opioids, corticosteroids, and benzodiazepines is independently associated with an increased risk of delirium in hospitalized cancer patients.
Adenosine triphosphate release and purinergic (P2) receptor-mediated secretion in small and large mouse cholangiocytes
Authors: Kangmee Woo, Meghana Sathe, Charles Kresge, Victoria Esser, Yoshiyuki Ueno, Julie Venter, Shannon S. Glaser, Gianfranco Alpini, Andrew P. Feranchak
Journal: Hepatology (2010)

Adenosine triphosphate (ATP) is released from cholangiocytes into bile and is a potent secretogogue by increasing intracellular Ca2+ and stimulating fluid and electrolyte secretion via binding purinergic (P2) receptors on the apical membrane. Although morphological differences exist between small and large cholangiocytes (lining small and large bile ducts, respectively), the role of P2 signaling has not been previously evaluated along the intrahepatic biliary epithelium. The aim of these studies therefore was to characterize ATP release and P2-signaling pathways in small (MSC) and large (MLC) mouse cholangiocytes. The findings reveal that both MSCs and MLCs express P2 receptors, including P2X4 and P2Y2. Exposure to extracellular nucleotides (ATP, uridine triphosphate, or 2′,3′-O-[4-benzoyl-benzoyl]-ATP) caused a rapid increase in intracellular Ca2+ concentration and in transepithelial secretion ( I sc) in both cell types, which was inhibited by the Cl− channel blockers 5-nitro-2-(-3-phenylpropylamino)-benzoic acid (NPPB) or niflumic acid. In response to mechanical stimulation (flow/shear or cell swelling secondary to hypotonic exposure), both MSCs and MLCs exhibited a significant increase in the rate of exocytosis, which was paralleled by an increase in ATP release. Mechanosensitive ATP release was two-fold greater in MSCs compared to MLCs. ATP release was significantly inhibited by disruption of vesicular trafficking by monensin in both cell types. Conclusion: These findings suggest the existence of a P2 signaling axis along intrahepatic biliary ducts with the “upstream” MSCs releasing ATP, which can serve as a paracrine signaling molecule to “downstream” MLCs stimulating Ca2+-dependent secretion. Additionally, in MSCs, which do not express the cystic fibrosis transmembrane conductance regulator, Ca2+-activated Cl− efflux in response to extracellular nucleotides represents the first secretory pathway clearly identified in these cholangiocytes derived from the small intrahepatic ducts. (Hepatology 2010)
Prolonged-release oxycodone–naloxone for treatment of severe pain in patients with Parkinson's disease (PANDA): a double-blind, randomised, placebo-controlled trial
Authors: Claudia Trenkwalder, K Ray Chaudhuri, Pablo Martinez-Martin, Olivier Rascol, Reinhard Ehret, Martin Vališ, Maria Sátori, Anna Krygowska-Wajs, Maria J Marti, Karen Reimer, Alexander Oksche, Mark Lomax, Julia DeCesare, Michael Hopp
Journal: The Lancet Neurology (2015)
Synchrotron X-ray microtomography (on a micron scale) provides three-dimensional imaging representation of bone ingrowth in calcium phosphate biomaterials
Authors: P Weiss, L Obadia, D Magne, X Bourges, C Rau, T Weitkamp, I Khairoun, J.M Bouler, D Chappard, O Gauthier, G Daculsi
Journal: Biomaterials (2003)
The Major Histocompatibility Complex-Restricted Antigen Receptor on T Cells
Authors: Kathryn Haskins, John Kappler, Philippa Marrack
Journal: Annual Review of Immunology (1984)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Treatment Decisions for Patients With Active Multiple Sclerosis
Authors: Olaf Stüve, Diego Centonze
Journal: JAMA Neurology (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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
Right heart, pulmonary, and left heart blood volumes determined by analogue computer analysis of radiocardiograms in normal subjects and patients with mitral stenosis
Authors: J. Perasalo, T. Heiskanen
Journal: Cardiovascular Research (1971)

By analysing the radiocardiograms with an analogue computer the right heart, pulmonary, and left heart blood volumes were determined in 15 subjects without cardiopulmonary disease and in 10 patients with mitral stenosis. The right and left heart blood volumes were both greater in the patients with mitral stenosis than in the normal subjects. The pulmonary blood volumes did not differ significantly in the groups studied. In the normal group the right and left heart blood volumes were almost equal. In patients with mitral stenosis the right heart blood volume was significantly greater than the left heart blood volume. The intracardiac blood volumes had a significant positive correlation with the radiographic heart volumes in both groups studied. The right heart blood volume had a positive correlation with the pulmonary blood volume in both groups; with the left heart blood volume this was the case only in the normal group.
Good Codons, Bad Transcript: Large Reductions in Gene Expression and Fitness Arising from Synonymous Mutations in a Key Enzyme
Authors: Deepa Agashe, N. Cecilia Martinez-Gomez, D. Allan Drummond, Christopher J. Marx
Journal: Molecular Biology and Evolution (2012)

Biased codon usage in protein-coding genes is pervasive, whereby amino acids are largely encoded by a specific subset of possible codons. Within individual genes, codon bias is stronger at evolutionarily conserved residues, favoring codons recognized by abundant tRNAs. Although this observation suggests an overall pattern of selection for translation speed and/or accuracy, other work indicates that transcript structure or binding motifs drive codon usage. However, our understanding of codon bias evolution is constrained by limited experimental data on the fitness effects of altering codons in functional genes. To bridge this gap, we generated synonymous variants of a key enzyme-coding gene in Methylobacterium extorquens. We found that mutant gene expression, enzyme production, enzyme activity, and fitness were all significantly lower than wild-type. Surprisingly, encoding the gene using only rare codons decreased fitness by 40%, whereas an allele coded entirely by frequent codons decreased fitness by more than 90%. Increasing gene expression restored mutant fitness to varying degrees, demonstrating that the fitness disadvantage of synonymous mutants arose from a lack of beneficial protein rather than costs of protein production. Protein production was negatively correlated with the frequency of motifs with high affinity for the anti-Shine-Dalgarno sequence, suggesting ribosome pausing as the dominant cause of low mutant fitness. Together, our data support the idea that, although a particular set of codons are favored on average across a genome, in an individual gene selection can either act for or against codons depending on their local context.
Matters Arising: HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis
Authors: S. Harney, B. P. Wordsworth, M A Brown, S. Laivoranta-Nyman, J. Ilonen, R. Hermann, T. Mttnen, A. Toivanen, J. Tuokko, R. Luukkainen, M. Hakala, P. Hannonen, M. Korpela, U. Yli-Kerthula
Journal: Annals of the Rheumatic Diseases (2005)

We read with great interest the paper by Laivoranta-Nyman et al.1 They studied Finnish patients with rheumatoid arthritis (RA) and controls, and suggested that there exist susceptibility, neutral and protective HLA-DR-DQ haplotypes that do not match the predictions of current hypotheses for the mechanism of association of the HLA class II region and RA...
PATTERNS OF SOCIAL INTERACTION IN BRAIN DISEASE
Authors: EDWIN A. WEINSTEIN, ROBERT L. KAHN
Journal: American Journal of Psychiatry (1956)

The phenomena of loss of insight, dulling of consciousness, and loss of inhibition occuring in patients with brain disease are described. These are not explicable solely in terms of a lesion in a particular portion of the brain or as the result of the disruption of a specific neurophysiological mechanism. These modes of behavior can be more fruitfully considered in terms of altered patterns of social interaction or language, appearing as modes of adaptation to the stress of illness and incapacity. The relationship of brain dysfunction to the premorbid personality and the cultural milieu is discussed.
Effects of MgADP on Length Dependence of Tension Generation in Skinned Rat Cardiac Muscle
Authors: Norio Fukuda, Hidetoshi Kajiwara, Shin’ichi Ishiwata, Satoshi Kurihara
Journal: Circulation Research (2000)

Abstract —The effect of MgADP on the sarcomere length (SL) dependence of tension generation was investigated using skinned rat ventricular trabeculae. Increasing SL from 1.9 to 2.3 μm decreased the muscle width by ≈11% and shifted the midpoint of the pCa-tension relationship (pCa 50 ) leftward by about 0.2 pCa units. MgADP (0.1, 1, and 5 mmol/L) augmented maximal and submaximal Ca 2+ -activated tension and concomitantly diminished the SL-dependent shift of pCa 50 in a concentration-dependent manner. In contrast, pimobendan, a Ca 2+ sensitizer, which promotes Ca 2+ binding to troponin C (TnC), exhibited no effect on the SL-dependent shift of pCa 50 , suggesting that TnC does not participate in the modulation of SL-dependent tension generation by MgADP. At a SL of 1.9 μm, osmotic compression, produced by 5% wt/vol dextran (molecular weight ≈464 000), reduced the muscle width by ≈13% and shifted pCa 50 leftward to a similar degree as that observed when increasing SL to 2.3 μm. This favors the idea that a decrease in the interfilament lattice spacing is the primary mechanism for SL-dependent tension generation. MgADP (5 mmol/L) markedly attenuated the dextran-induced shift of pCa 50 , and the degree of attenuation was similar to that observed in a study of varying SL. The actomyosin-ADP complex (AM.ADP) induced by exogenous MgADP has been reported to cooperatively promote myosin attachment to the thin filament. We hereby conclude that the increase in the number of force-generating crossbridges on a decrease in the lattice spacing is masked by the cooperative effect of AM.ADP, resulting in depressed SL-dependent tension generation. The full text of this article is available at http://www.circresaha.org.
Oral vaccination. Identification of classes of proteins that provoke an immune response upon oral feeding.
Authors: H J de Aizpurua, G J Russell-Jones
Journal: The Journal of Experimental Medicine (1988)

Oral immunization of an animal is generally hard to achieve unless large quantities of antigen are administered. In this study a number of antigens were tested for their ability to elicit a systemic immune response upon oral administration. It was found that bacterial pili, LTB, lectins, and a viral hemagglutinin were all able to elicit significant antibody titers upon oral feeding. The immune response thus generated to LTB and K99 pili could be completely abolished by cofeeding a number of sugars that have close structural homology to the terminal sugars of the GM1 and GM2 gangliosides to which these molecules are known to bind. All of the proteins that were active in oral immunization are known to possess "lectin or lectin-like" binding activities. It is therefore proposed that these molecules are able to bind to glycolipids and glycoproteins on the intestinal mucosa and to stimulate these cells to transport the proteins into the systemic circulation, thereby eliciting a systemic immune response. Molecules that did not possess this binding activity were unable to elicit significant responses at the doses tested.