tbuckley/cabot-search huggingface dataset:
Atorvastatin in Patients with Type 2 Diabetes Mellitus Undergoing Hemodialysis
Authors: Christoph Wanner, Vera Krane, Winfried März, Manfred Olschewski, Johannes F.E. Mann, Günther Ruf, Eberhard Ritz
Journal: New England Journal of Medicine (2005)

Statins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus. However, the benefit of statins in such patients receiving hemodialysis, who are at high risk for cardiovascular disease and death, has not been examined.We conducted a multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were randomly assigned to receive 20 mg of atorvastatin per day or matching placebo. The primary end point was a composite of death from cardiac causes, nonfatal myocardial infarction, and stroke. Secondary end points included death from all causes and all cardiac and cerebrovascular events combined.After four weeks of treatment, the median level of low-density lipoprotein cholesterol was reduced by 42 percent among patients receiving atorvastatin, and among those receiving placebo it was reduced by 1.3 percent. During a median follow-up period of four years, 469 patients (37 percent) reached the primary end point, of whom 226 were assigned to atorvastatin and 243 to placebo (relative risk, 0.92; 95 percent confidence interval, 0.77 to 1.10; P=0.37). Atorvastatin had no significant effect on the individual components of the primary end point, except that the relative risk of fatal stroke among those receiving the drug was 2.03 (95 percent confidence interval, 1.05 to 3.93; P=0.04). Atorvastatin reduced the rate of all cardiac events combined (relative risk, 0.82; 95 percent confidence interval, 0.68 to 0.99; P=0.03, nominally significant) but not all cerebrovascular events combined (relative risk, 1.12; 95 percent confidence interval, 0.81 to 1.55; P=0.49) or total mortality (relative risk, 0.93; 95 percent confidence interval, 0.79 to 1.08; P=0.33).Atorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death, nonfatal myocardial infarction, and stroke in patients with diabetes receiving hemodialysis.
The Neurobiology of Individual Differences in Complex Behavioral Traits
Authors: Ahmad R. Hariri
Journal: Annual Review of Neuroscience (2009)

Neuroimaging, especially BOLD fMRI, has begun to identify how variability in brain function contributes to individual differences in complex behavioral traits. In parallel, pharmacological fMRI and multimodal PET/fMRI are identifying how variability in molecular signaling pathways influences individual differences in brain function. Against this background, functional genetic polymorphisms are being utilized to understand the origins of variability in signaling pathways as well as to model efficiently how such emergent variability impacts behaviorally relevant brain function. This article provides an overview of a research strategy seeking to integrate these complementary technologies and utilizes existing empirical data to illustrate its effectiveness in illuminating the neurobiology of individual differences in complex behavioral traits. The article also discusses how such efforts can contribute to the identification of predictive markers that interact with environmental factors to precipitate disease and to develop more effective and individually tailored treatment regimes.
Disappearance of certain acidic organelles (endosomes and Langerhans cell granules) accompanies loss of antigen processing capacity upon culture of epidermal Langerhans cells.
Authors: H Stössel, F Koch, E Kämpgen, P Stöger, A Lenz, C Heufler, N Romani, G Schuler
Journal: The Journal of Experimental Medicine (1990)

Freshly isolated epidermal Langerhans cells (LC) can actively process native protein antigens, but are weak in sensitizing helper T cells. During culture, when LC mature into potent immunostimulatory dendritic cells, T cell sensitizing capacity develops but antigen processing capacity is downregulated. Processing of exogenous antigens for class II-restricted antigen presentation involves acidic organelles. We used the DAMP-technique to monitor acidic organelles at the ultrastructural level in fresh, as well as cultured, mouse and human LC. We observed that the loss of antigen processing capacity with culture of LC was reflected by the disappearance of certain acidic organelles, namely endosomes (particularly early ones), and the hitherto enigmatic LC granules ("Birbeck Granules"). Our findings support the notion that endosomes are critical for antigen processing and suggest that LC granules might be involved as well.
Micro- and Nanoscale Engineering of Cell Signaling
Authors: L.C. Kam, K. Shen, M.L. Dustin
Journal: Annual Review of Biomedical Engineering (2013)

It is increasingly recognized that cell signaling, as a chemical process, must be considered at the local, micrometer scale. Micro- and nanofabrication techniques provide access to these dimensions, with the potential to capture and manipulate the spatial complexity of intracellular signaling in experimental models. This review focuses on recent advances in adapting surface engineering for use with biomolecular systems that interface with cell signaling, particularly with respect to surfaces that interact with multiple receptor systems on individual cells. The utility of this conceptual and experimental approach is demonstrated in the context of epithelial cells and T lymphocytes, two systems whose ability to perform their physiological function is dramatically impacted by the convergence and balance of multiple signaling pathways.
SOD1 in Cerebral Spinal Fluid as a Pharmacodynamic Marker for Antisense Oligonucleotide Therapy
Authors: Leah Winer, Dushyanth Srinivasan, Seung Chun, David Lacomis, Matthew Jaffa, Anne Fagan, David M. Holtzman, Ed Wancewicz, C. Frank Bennett, Robert Bowser, Merit Cudkowicz, Timothy M. Miller
Journal: JAMA Neurology (2012)

Therapies designed to decrease the level of SOD1 are currently in a clinical trial for patients with superoxide dismutase (SOD1)-linked familial amyotrophic lateral sclerosis (ALS).To determine whether the SOD1 protein in cerebral spinal fluid (CSF) may be a pharmacodynamic marker for antisense oligonucleotide therapy and a disease marker for ALS.Antisense oligonucleotides targeting human SOD1 were administered to rats expressing SOD1G93A. The human SOD1 protein levels were measured in the rats' brain and CSF samples. In human CSF samples, the following proteins were measured: SOD1, tau, phosphorylated tau, VILIP-1, and YKL-40.Ninety-three participants with ALS, 88 healthy controls, and 89 controls with a neurological disease (55 with dementia of the Alzheimer type, 19 with multiple sclerosis, and 15 with peripheral neuropathy).Antisense oligonucleotide-treated SOD1G93A rats had decreased human SOD1 messenger RNA levels (mean [SD] decrease of 69% [4%]) and decreased protein levels (mean [SD] decrease of 48% [14%]) in the brain. The rats' CSF samples showed a similar decrease in hSOD1 levels (mean [SD] decrease of 42% [14%]). In human CSF samples, the SOD1 levels varied a mean (SD) 7.1% (5.7%) after additional measurements, separated by months, were performed. The CSF SOD1 levels were higher in the participants with ALS (mean [SE] level, 172 [8] ng/mL; P<.05) and the controls with a neurological disease (mean [SE] level, 172 [6] ng/mL; P<.05) than in the healthy controls (mean [SE] level, 134 [4] ng/mL). Elevated CSF SOD1 levels did not correlate with disease characteristics in participants with ALS or controls with dementia of the Alzheimer type, but they did correlate with tau, phosphorylated tau, VILIP-1 and YKL-40 levels in controls with dementia of the Alzheimer type.SOD1 in CSF may be an excellent pharmacodynamic marker for SOD1-lowering therapies because antisense oligonucleotide therapy lowers protein levels in the rat brain and rat CSF samples and because SOD1 levels in CSF samples from humans are stable over time.
THE IMPORTANCE OF CONSTITUTION IN PSYCHIATRY
Authors: G. LANGFELDT
Journal: American Journal of Psychiatry (1953)

Heredity investigations, normal characterology, and clinical experience speak strongly in favor of the existence of well defined types of constitution that play an important role in pathology and criminology. By constitution is here meant the total psycho-biological outfit of an individual that is so fixed that it can scarcely be changed except by long-lasting psychical or physical influences. The constitutional types most frequently met with in clinical psychiatry are the sensitive, the cyclothymic and schizoid, the hysterical, the compulsive, and the paranoic and paranoid constitutions. The author is personally of the opinion that the fundamental and central traits in all these character types are of hereditary origin and does not think that psychotherapy, even at an early stage, will have any great influence in changing these personalities, except perhaps in the hysterical and possibly the paranoic types. A common trait in all these constitutional types is the disposition to many neurotic as well as psychotic reactions, which can be understood either as exaggeration of the character traits in question or by assumption of the relatively simple psychodynamic processes of introjection, conversion, or projection. During life many psychoneurotic mechanisms may take place in these individuals and this is the reason that many of them may profit from psychotherapy. The sensitive constitution is supposed by the author to be the basis for development of the simple depressive reactions, self-reference reactions, and inhibition reactions, as well as for several of the compulsive neuroses, that are not developed on the basis of a compulsive character. In addition the author assumes that most of the paranoic reactions are also due to a hypersensitive constitution. While the symptoms in the sensitive neuroses are best explained by assuming a tendency toward introjection, in the paranoics we have to do with sensitive individuals with, probably, an inborn tendency toward projection. As to the relation between the hysterical character and the symptom formations in the hysterical neuroses, these are, as is generally agreed, best explained by the assumption of a tendency to convert the conflict into bodily symptoms. And as to the symptoms in the cycloid and schizoid characters, these are best explained as direct hereditary character traits, while the symptom formation in the reactive psychoses is best explained as an exaggeration of the character traits. The author believes it is tremendously important to try to diagnose and differentiate the constitutional types. This enables one to understand the personality itself as well as the pathological reactions without any deeper analysis being necessary. Study of the constitutional types gives the best clues to the question of the prognosis of the various reactions; likewise, a knowledge of the constitutional type behind the reactions helps to safe-guard against false diagnosis, especially of schizophrenia.
Ser-249 p53 Mutations in Plasma DNA of Patients With Hepatocellular Carcinoma From The Gambia
Authors: Gregory D. Kirk, Anne-Marie Camus-Randon, Maimuna Mendy, James J. Goedert, Philippe Merle, Christian Trépo, Christian Bréchot, Pierre Hainaut, Ruggero Montesano
Journal: JNCI Journal of the National Cancer Institute (2000)

A selective mutation, an arginine-to-serine substitution in codon 249, of the p53 gene has been identified as a "hotspot" mutation in hepatocellular carcinoma (HCC). This mutation occurs in populations that are exposed to aflatoxins and have a high prevalence of hepatitis B virus carriers. We evaluated whether this mutation could be detected in cell-free DNA isolated from the plasma of subjects from The Gambia to detect this mutation that is strongly associated with HCC.Fifty-three patients with HCC, 13 patients with cirrhosis, and 53 control subjects were prospectively recruited from The Gambia. Sixty patients, of non-African origin, with various liver pathologies were also selected from France. DNA was extracted and purified from 200-microL aliquots of plasma. The Ser-249 p53 mutation was detected by restriction endonuclease digestion of polymerase chain reaction products from exon 7 and was confirmed by direct sequencing of the amplified DNA.The Ser-249 p53 mutation was detected in plasma DNA from 19 (36%) of the 53 patients with HCC, two (15%) of the 13 patients with cirrhosis, and three (6%) of the 53 control subjects. This mutation was not detected in any plasma DNA from the European patients. The adjusted odds ratio for having the mutation was 16.4 (95% confidence interval = 3.0-90.5) for patients with HCC compared with the control subjects.The Ser-249 p53 mutation in plasma DNA is strongly associated with HCC in Gambian patients. This mutation was also detected at a much lower prevalence in plasma DNA from Gambian patients with cirrhosis and in Gambian control subjects, findings that may lead to the earlier detection of HCC. Use of the Ser-249 p53 mutation should facilitate further molecular epidemiologic studies on the development of HCC.
Bisphosphonate-related osteonecrosis of the jaw (BRONJ): run dental management designs and issues in diagnosis
Authors: G. Campisi, O. Di Fede, A. Musciotto, A. Lo Casto, L. Lo Muzio, F. Fulfaro, G. Badalamenti, A. Russo, N. Gebbia
Journal: Annals of Oncology (2007)
Localisation of atopy and β subunit of high-affinity IgE receptor (Fc&amp;isin;RI) on chromosome 11q
Authors: A.J. Sandford, T. Shirakawa, M.F. Moffat, S.E. Daniels, J.A. Faux, R.P. Young, W.O.C.M. Cookson, C. Ra, Y. Nakamura, G.M. Lathrop, J.M. Hopkin
Journal: The Lancet (1993)
Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review
Authors: J Avouac
Journal: Annals of the Rheumatic Diseases (2005)

<h3>Objective.</h3> To examine the mortality and cardiovascular disease (CVD) burden among a population-based cohort of patients with systemic lupus erythematosus (SLE) with previously described late mean onset and low rates of organ-threatening disease. <h3>Methods.</h3> This retrospective population-based cohort study investigated incident cases of SLE diagnosed from 1991–2008 and followed through March 2009 to examine rates of death and CVD events: myocardial infarction, stroke, or congestive heart failure hospitalization. Cases were identified using the 1997 update of the 1982 American College of Rheumatology SLE criteria. Searches included electronic records, chart audits, and state death matches, with physician review. Age-matched and sex-matched population comparisons facilitated relative event rate calculations. <h3>Results.</h3> Seventy incident SLE cases had late mean onset (52 years), with an incidence of 5 cases per 100,000/year. Matched comparisons showed similar baseline rates of hypertension, hyperlipidemia, and diabetes. However, patients with SLE experienced more CVD in the 2 years preceding SLE diagnosis (OR 3.8, 95% CI 1.8, 8.0). The estimated 10-year mortality rates were 26% for SLE subjects versus 19% for comparisons, hazard ratio (HR) 2.1, p &lt; 0.01. Adjusted for prior CVD, SLE cases still demonstrated increased hazards of mortality (HR 1.9, p = 0.01) and CVD event or death (HR 1.8, p = 0.01). <h3>Conclusion.</h3> This incident SLE cohort demonstrated nearly doubled mortality and CVD event hazards compared to age-matched and sex-matched comparisons, even after accounting for higher CVD events in the 2 years preceding SLE diagnosis. This raises research questions regarding delayed SLE diagnosis versus accelerated CVD prior to SLE, particularly in older-onset SLE.
Anemia in Critical Illness
Authors: Shailaja J. Hayden, Tyler J. Albert, Timothy R. Watkins, Erik R. Swenson
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Anemia is common in the intensive care unit, and may be associated with adverse consequences. However, current options for correcting anemia are not without problems and presently lack convincing efficacy for improving survival in critically ill patients. In this article we review normal red blood cell physiology; etiologies of anemia in the intensive care unit; its association with adverse outcomes; and the risks, benefits, and efficacy of various management strategies, including blood transfusion, erythropoietin, blood substitutes, iron therapy, and minimization of diagnostic phlebotomy.
Molecular genetic testing of a fetus at risk of Gerstmann-Sträussler-Scheinker syndrome
Authors: Paul Brown, Larisa Cervenáková, LevG. Goldfarb, D.Carleton Gajdusek, Albert Haverkamp, Carole Haverkamp, Juli Horwitz, StevenD. Creacy, RobertA. Bever, Paul Wexler, Eva Sujansky, RandallJ. Bjork
Journal: The Lancet (1994)
Hepatitis C Virus Proteins Modulate MicroRNA Expression and Chemosensitivity in Malignant Hepatocytes
Authors: Chiara Braconi, Nicola Valeri, Pierluigi Gasparini, Nianyuan Huang, Cristian Taccioli, Gerard Nuovo, Tetsuro Suzuki, Carlo Maria Croce, Tushar Patel
Journal: Clinical Cancer Research (2010)

Hepatocellular cancer (HCC) is highly resistant to chemotherapy and is associated with poor prognosis. Chronic hepatitis C virus (HCV) infection is a major cause of HCC. However, the effect of viral proteins in mediating chemosensitivity in tumor cells is unknown. We postulated that HCV viral proteins could modulate therapeutic responses by altering host cell microRNA (miRNA) expression.HepG2 malignant hepatocytes were stably transfected with full-length HCV genome (Hep-394) or an empty vector (Hep-SWX). MiRNA profiling was done by using a custom microarray, and the expression of selected miRNAs was validated by real-time PCR. Protein expression was assessed by Western blotting, whereas caspase activation was assessed by a luminometric assay.The IC(50) to sorafenib was lower in Hep-394 compared with Hep-SWX control cells. Alterations in miRNA expression occurred with 10 miRNAs downregulated >2-fold and 23 miRNAs upregulated >2-fold in Hep-394 cells compared with controls. Of these, miR-193b was overexpressed by 5-fold in Hep-394 cells. miR-193b was predicted to target Mcl-1, an antiapoptotic protein that can modulate the response to sorafenib. The expression of Mcl-1 was decreased, and basal caspase-3/7 activity and poly ADP ribose polymerase cleavage were increased in Hep-394 cells compared with controls. Moreover, transfection with precursors to miR-193b decreased both Mcl-1 expression and the IC(50) to sorafenib.Cellular expression of full-length HCV increases sensitivity to sorafenib by the miRNA-dependent modulation of Mcl-1 and apoptosis. Modulation of miRNA responses may be a useful strategy to enhance response to chemotherapy in HCC.
EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia
Authors: M Konantz, M C André, M Ebinger, M Grauer, H Wang, S Grzywna, O C Rothfuss, S Lehle, O S Kustikova, H R Salih, R Handgretinger, F Fend, C Baum, L Kanz, L Quintanilla-Martinez, K Schulze-Osthoff, F Essmann, C Lengerke
Journal: Leukemia (2012)
Low-Gradient Aortic Stenosis
Authors: Jean-Luc Monin, Jean-Paul Quéré, Mehran Monchi, Hélène Petit, Serge Baleynaud, Christophe Chauvel, Camélia Pop, Patrick Ohlmann, Claude Lelguen, Patrick Dehant, Christophe Tribouilloy, Pascal Guéret
Journal: Circulation (2003)

The prognostic value of dobutamine stress hemodynamic data in the setting of low-gradient aortic stenosis has been addressed in small, single-center studies. Larger studies are needed to define the criteria for selecting the patients who will benefit from valve replacement.Six centers prospectively enrolled 136 patients with aortic stenosis (96 men; median age, 72 years [range, 65 to 77 years]; median aortic valve area, 0.7 cm2 [range, 0.6 to 0.8]; mean transaortic gradient, 29 mm Hg [range, 23 to 34 mm Hg]; cardiac index, 2.11 L x min(-1) x m(-2) [range, 1.75 to 2.55 L x min(-1) x m(-2)]). Left ventricular contractile reserve on the dobutamine stress Doppler study was present in 92 patients (group I) and absent in 44 patients (group II). Operative mortality was 5% (3 of 64 patients) in group I compared with 32% (10 of 31 patients) in group II (P=0.0002). Predictors for operative mortality were the lack of contractile reserve (odds ratio, 10.9; 95% confidence interval [CI], 2.6 to 43.4; P=0.001) and a mean transaortic gradient < or =20 mm Hg (odds ratio, 4.7; 95% CI, 1.1 to 21.0; P=0.04). Predictors for long-term survival were valve replacement (hazard ratio, 0.30; 95% CI, 0.17 to 0.53; P=0.001) and left ventricular contractile reserve (hazard ratio, 0.40; 95% CI, 0.23 to 0.69; P=0.001).In the setting of low-gradient aortic stenosis, surgery seems beneficial for most of the patients with left ventricular contractile reserve. In contrast, the postoperative outcome of patients without reserve is compromised by a high operative mortality. Thus, dobutamine stress Doppler hemodynamics may be factored into the risk-benefit analysis for each patient.
Comparison of a Custom-made and a Thermoplastic Oral Appliance for the Treatment of Mild Sleep Apnea
Authors: Olivier M. Vanderveken, Annick Devolder, Marie Marklund, An N. Boudewyns, Marc J. Braem, Walter Okkerse, Johan A. Verbraecken, Karl A. Franklin, Wilfried A. De Backer, Paul H. Van de Heyning
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: The efficacy of immediate adaptation of mandibular advancement devices made of thermoplastic material as a treatment option for sleep-disordered breathing (SDB) has been demonstrated in clinical studies. To date, there have been no studies comparing the efficacy of such prefabricated devices with custom-made devices.Objectives: Our purpose was to compare the efficacy of both types of devices in patients with SDB.Methods: A randomized controlled cross-over trial, comprising 4 months of treatment with a thermoplastic and a custom-made device, with a 1-month washout interval.Measurements and Main Results: A total of 35 patients (29 males; age, 49 ± 9 yr; apnea–hypopnea index [AHI], 13 ± 11 events/h; body mass index, 28 ± 4 kg/m2) completed the protocol. AHI was only reduced with the custom-made device (P = 0.005). In addition, this device reduced snoring to a greater extent than the thermoplastic device. The success rate was higher with the custom-made device (60 vs. 31%; P = 0.02). One-third of the patients demonstrated compliance failure with the thermoplastic device, mainly because of insufficient overnight retention. Total failure rate with the thermoplastic device was 69%, whereas the majority (63%) of these were successfully treated with the custom-made device. At the end of the study, 82% of the patients preferred the custom-made device, and 9% had no preference (P < 0.0001).Conclusions: In this study, a custom-made device turned out to be more effective than a thermoplastic device in the treatment of SDB. Our results suggest that the thermoplastic device cannot be recommended as a therapeutic option nor can it be used as a screening tool to find good candidates for mandibular advancement therapy.