tbuckley/cabot-search huggingface dataset:
Importance of Nucleic Acid Recognition in Inflammation and Autoimmunity
Authors: Franck J. Barrat, Keith B. Elkon, Katherine A. Fitzgerald
Journal: Annual Review of Medicine (2015)

An important concept in immunology is the classification of immune responses as either innate or adaptive, based on whether the antigen receptors are encoded in the germline or generated somatically by gene rearrangement. The innate immune system is an ancient mode of immunity, and by being a first layer in our defense against infectious agents, it is essential for our ability to develop rapid and sustained responses to pathogens. We discuss the importance of nucleic acid recognition by the innate immune system to mounting an appropriate immune response to pathogens and also how inflammation driven by uncontrolled recognition of self-nucleic acids can lead to autoimmune diseases. We also summarize current efforts to either harness the immune system using agonists of nucleic acid–specific innate sensors or, on the contrary, by using inhibitors in autoimmune situations.
International travel and acquisition of multidrug-resistant Enterobacteriaceae: a systematic review
Authors: Robert Jan Hassing, Jelmer Alsma, Maris S. Arcilla, Perry J. van Genderen, Bruno H. Stricker, Annelies Verbon
Journal: Eurosurveillance (2015)

International travel is considered to be an important risk factor for acquisition of multidrug-resistant Enterobacteriaceae (MRE). The aim of this systematic review was to determine the effect of international travel on the risk of post-travel faecal carriage of MRE. Secondary outcomes were risk factors for acquisition of MRE. A systematic search for relevant literature in seven international databases was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles needed to report on (i) foreign travel, (ii) screening of asymptomatic participants, (iii) antimicrobial susceptibility data and (iv) faecal Enterobacteriaceae carriage. Two researchers independently screened the abstracts, assessed the full article texts for eligibility and selected or rejected them for inclusion in the systematic review. In case of disagreement, a third researcher decided on inclusion. Eleven studies were identified. In all studies, a high prevalence (&gt; 20%) of carriage of MRE after international travel was found. The highest prevalence was observed in travellers returning from southern Asia. Foreign travel was associated with an increased risk of carriage of MRE. Further research is needed to assess if this leads to an increase in the number of infections with MRE. Systematic review registration number: PROSPERO CRD42015024973.
Iron–Sulfur Cluster Biogenesis Chaperones: Evidence for Emergence of Mutational Robustness of a Highly Specific Protein–Protein Interaction
Authors: Wojciech Delewski, Bogumiła Paterkiewicz, Mateusz Manicki, Brenda Schilke, Bartłomiej Tomiczek, Szymon J. Ciesielski, Lukasz Nierzwicki, Jacek Czub, Rafal Dutkiewicz, Elizabeth A. Craig, Jaroslaw Marszalek
Journal: Molecular Biology and Evolution (2015)

Biogenesis of iron–sulfur clusters (FeS) is a highly conserved process involving Hsp70 and J-protein chaperones. However, Hsp70 specialization differs among species. In most eukaryotes, including Schizosaccharomyces pombe, FeS biogenesis involves interaction between the J-protein Jac1 and the multifunctional Hsp70 Ssc1. But, in Saccharomyces cerevisiae and closely related species, Jac1 interacts with the specialized Hsp70 Ssq1, which emerged through duplication of SSC1. As little is known about how gene duplicates affect the robustness of their protein interaction partners, we analyzed the functional and evolutionary consequences of Ssq1 specialization on the ubiquitous J-protein cochaperone Jac1, by comparing S. cerevisiae and S. pombe. Although deletion of JAC1 is lethal in both species, alanine substitutions within the conserved His–Pro–Asp (HPD) motif, which is critical for Jac1:Hsp70 interaction, have species-specific effects. They are lethal in S. pombe, but not in S. cerevisiae. These in vivo differences correlated with in vitro biochemical measurements. Charged residues present in the J-domain of S. cerevisiae Jac1, but absent in S. pombe Jac1, are important for tolerance of S. cerevisiae Jac1 to HPD alterations. Moreover, Jac1 orthologs from species that encode Ssq1 have a higher sequence divergence. The simplest interpretation of our results is that Ssq1's coevolution with Jac1 resulted in expansion of their binding interface, thus increasing the efficiency of their interaction. Such an expansion could in turn compensate for negative effects of HPD substitutions. Thus, our results support the idea that the robustness of Jac1 emerged as consequence of its highly efficient and specific interaction with Ssq1.
Traumatic neurosis in the etiology of alcoholism: Viet Nam combat and other trauma
Authors: R B Lacoursiere, K E Godfrey, L M Ruby
Journal: American Journal of Psychiatry (1980)

Traumatic neurosis from Viet Nam combat or other sources includes many symptoms that can be effectively self-medicated with alcohol, at least initially. These symptoms include chronic anxiety and restlessness, insomnia, and recurrent frightening dreams. Repeated self-medication with alcohol results in tolerance and a need to increase the amount consumed. Attempts to decrease consumption or to abstain can lead to alcohol withdrawal symptoms similar to and exacerbating the initial symptoms of traumatic neurosis. Continuing alcohol use, with the establishment of a vicious circle, can follow. The authors present three case examples. They note that treatment of alcoholism under the conditions described requires specific attention to the underlying traumatic neurosis.
Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues.
Authors: F T Stevenson, S L Bursten, R M Locksley, D H Lovett
Journal: The Journal of Experimental Medicine (1992)

NH2-terminal glycine myristyl acylation is a cotranslational modification that affects both protein localization and function. However, several proteins that lack NH2-terminal glycine residues, including the interleukin 1 (IL-1) precursors, also contain covalently linked myristate. To date, the site(s) of acylation of these proteins has not been determined. During an evaluation of IL-1 acylation, it was observed that [3H]myristate-labeled human monocyte lysates contained a prominent 26-kD myristylated protein, which was identified as the tumor necrosis factor alpha (TNF) precursor protein on the basis of specific immune precipitation. Radioimmunoprecipitates from the supernates of labeled monocytes indicated that the processed or mature 17-kD form of TNF does not contain myristate, suggesting that the site of acylation occurs within the 76-amino acid propiece of the precursor molecule. As the TNF precursor does not contain an NH2-terminal glycine, we hypothesized that myristyl acylation occurs on the N-epsilon-NH2 groups of lysine, of which two are present in the propiece (K19K20). Synthetic peptides were designed to include all seven lysine residues present within the entire 26-kD TNF precursor, and used in an in vitro myristyl acylation assay containing peptide, myristyl-CoA, and monocyte lysate as a source of enzyme. Analysis of reaction products by reverse phase high performance liquid chromatography and gas phase sequencing demonstrated the exclusive myristyl acylation of K19 and K20, consistent with the presence in monocytes of a specific lysyl N-epsilon-NH2-myristyl transferase activity. The acylated lysine residues are located immediately downstream from a hydrophobic, probable membrane-spanning segment of the propiece. Specific myristyl acylation of the TNF propiece may facilitate membrane insertion or anchoring of this critical inflammatory mediator.
TAP-independent, beta 2-microglobulin-dependent surface expression of functional mouse CD1.1.
Authors: R R Brutkiewicz, J R Bennink, J W Yewdell, A Bendelac
Journal: The Journal of Experimental Medicine (1995)

CD1 molecules consist of beta 2-microglobulin (beta 2m) noncovalently complexed to a non-major histocompatibility complex (MHC)-encoded monomorphic integral membrane protein homologous to MHC class I alpha chains. Little is known about the requirements for cell surface expression and T cell recognition of CD1. We inserted the mouse CD1.1 gene into vaccinia virus to create a recombinant virus expressing CD1.1 under the control of a viral promoter. Using this recombinant virus to infect normal or mutant cell lines, we found that the expression of molecules reactive with the CD1.1-specific monoclonal antibody 3C11 requires the expression of beta 2m but was not affected by the absence of the MHC-encoded peptide transporter (TAP). Consistent with these results, IL-2 production by the mCD1.1-specific T cell hybridoma DN32.D3 was induced by thymocytes from normal mice or mice with a homozygous deletion of the TAP1 gene, but not by thymocytes from mice with a homozygous deletion of the beta 2m gene. These results indicate that expression of functional mCD1.1 occurs in a beta 2m-dependent, TAP-independent manner.
The minimal important difference for the St George's Respiratory Questionnaire in patients with severe COPD
Authors: Jorrit B.A. Welling, Jorine E. Hartman, Nick H.T. Ten Hacken, Karin Klooster, Dirk-Jan Slebos
Journal: European Respiratory Journal (2015)

The St George's Respiratory Questionnaire (SGRQ) is a validated, commonly used questionnaire for measuring quality of life in patients with chronic obstructive pulmonary disease (COPD). The current established minimal important difference (MID) for SGRQ scores in an average COPD population is −4 units. However, for patients with severe COPD, the MID has not been thoroughly validated. We re-determined the SGRQ MID for this patient group. 115 severe COPD patients (forced expiratory volume in 1 s (FEV 1 ) 26±9% of predicted, SGRQ score 62±11 units; mean± sd ,) who participated in seven different bronchoscopic lung volume reduction clinical trials were included in the analysis. Anchor- and distribution-based methods were used to define the MID for SGRQ scores. FEV 1 , 6-min walk distance and residual volume were used as anchors. Combining both anchor- and distribution-based methods, we identified a SGRQ MID of −8.3 units at 1 month and −7.1 units at 6 months. This study proposes an alternative SGRQ MID for patients with severe COPD of −8.3 units at 1 month and −7.1 units at 6 months follow-up after intervention. Our new MID estimates could be applied for both interpreting SGRQ outcomes as well as sample size determination in future clinical trials investigating interventions in severe COPD patients.
Dancing Jaw and Dancing Eyes
Authors: Roger Kalla, Jurka Meichtry, Rahel Schumacher, Dario Cazzoli, Roland Wiest, Eberhard Seifert, Rene Müri
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
Intraspecific DNA divergence in Drosophila: a study on parthenogenetic D. mercatorum.
Authors: A Caccone, G D Amato, J R Powell
Journal: Molecular Biology and Evolution (1987)

Drosophila mercatorum is a species that can give rise to totally homozygous parthenogenetic strains. Using the technique of DNA-DNA hybridization, we have assessed the overall single-copy DNA differences among three independently derived strains that represent three independent genomes. Among strains, the average difference between homoduplex and heteroduplex median melting temperatures is 1.3 degrees C. This represents greater than or equal to 1.3% base-pair mismatch. Normalized percent of reassociation indicates further genetic differences, probably reflecting insertion/deletion differences and/or regions of the genome that are highly variable. This overall intraspecific genetic variation is higher than generally is thought to exist but is consistent with growing evidence of extensive DNA diversity within species of invertebrates. High intraspecific DNA variation may be correlated with rapid phyletic rates of evolution. Because of this high level of variation, the technique of DNA-DNA hybridization may be used to study intraspecific variation in invertebrates but is limited in its usefulness for higher systematic studies.
California’s assembly passes physician assisted dying bill
Authors: Owen Dyer
Journal: BMJ (2015)

California looks set to permit physician assisted dying next year after its state assembly passed the End of Life Option Act by 43 votes to 34 on 9 September. The legislation is closely modeled on the Oregon law that has permitted terminally ill patients to end their life in that state since 1997. Only patients who file two written requests and have less than six months to live can avail themselves of the law.

The bill had stalled earlier this year in committee, and was not expected to pass this year, …
Abstract 17150: Hematopoietic Progenitor Cells Expressing CD34+ and CD133+ Surface Markers are Predictors of Adverse Cardiovascular Outcomes in a Population with Coronary Artery Disease
Authors: Riyaz S Patel, Danny J Eapen, Qunna Li, Lauren M Owens, Ayaz Rahman, Pankaj Manocha, Hatem Al Kassem, Ayman Samman Tahhan, Muhammad Hammadah, Hilary Rosenthal, Wayne Harris, Emir Veledar, A Maziar Zafari, Viola Vaccarino, Habib Samady, Edmund K Waller, Arshed Quyyumi
Journal: Circulation (2012)

Background: Circulating progenitor cell (PCs) levels may reflect intrinsic regenerative/ reparative potential. We hypothesized that that low levels of early PC sub-populations will be associated wi...
ACC/AHA guidelines for the management of patients with valvular heart disease
Authors: RobertO. Bonow, Blase Carabello, AntonioC. de Leon, L.Henry Edmunds, BradleyJ. Fedderly, MichaelD. Freed, WilliamH. Gaasch, CharlesR. McKay, RickA. Nishimura, PatrickT. O’Gara, RobertA. O’Rourke, ShahbudinH. Rahimtoola, JamesL. Ritchie, MelvinD. Cheitlin, KimA. Eagle, TimothyJ. Gardner, Arthur Garson, RaymondJ. Gibbons, RobertA. O’Rourke, RichardO. Russell, ThomasJ. Ryan, SidneyC. Smith
Journal: Journal of the American College of Cardiology (1998)
L1 A-monomer tandem arrays have expanded during the course of mouse L1 evolution.
Authors: S A Schichman, N B Adey, M H Edgell, C A Hutchison
Journal: Molecular Biology and Evolution (1993)

LINE-1 (L1) is a family of highly repeated DNA sequences interspersed throughout the mammalian genome. Individual L1 elements are thought to be generated by a transposition mechanism involving reverse transcription of an RNA intermediate followed by insertion into a new genomic site. In mice, three major families of L1 elements, termed "A," "F," and "V," have been defined on the basis of the sequence found at the 5' terminus. Previous analyses of A-monomers have demonstrated sequence heterogeneity among individual A-monomers, variation in the length of A-monomer sequences, and the presence of transcriptional regulatory activity. To provide a detailed characterization of A-monomers as a foundation for studying their transcriptional regulatory activity, we have analyzed the sequences of 39 complete or partial length A-monomers from 20 different mouse L1 elements. A-monomers can be classified into six different types according to shared-sequence length variations. Consensus sequences for the six types of A-monomers indicate conservation of possible transcription factor-binding sequences. Specific subgroups of A-monomers correlate with the relative dispersal time of a mouse L1 element. A phylogenetic analysis of A-monomers indicates that the length variants represent good diagnostic sites for phylogenetic subgroups of A-monomer sequences. These observations suggest a model for the evolution of A-monomer tandem arrays that involves stepwise mutation and array expansion in the 5' direction. Hybridization data provide a minimum estimate of 16,000 copies of the A-monomer sequence in the mouse haploid genome, with an average array length of 2.1 monomer units.
Intrinsic functional defects of type 2 innate lymphoid cells impair innate allergic inflammation in promyelocytic leukemia zinc finger (PLZF)–deficient mice
Authors: Philip A. Verhoef, Michael G. Constantinides, Benjamin D. McDonald, Joseph F. Urban, Anne I. Sperling, Albert Bendelac
Journal: Journal of Allergy and Clinical Immunology (2015)
Corticosteroids in ARDS
Authors: Paul Marik, Stephen Pastores, Djillali Annane
Journal: New England Journal of Medicine (2006)

ARDS. 2,4 Mortality is overall improved with prolonged glucocorticoid treatment (91 of 276 patients; 33%; vs 111 of 242 patients; 46%; relative risk [RR], 0.76; 95% confidence interval [CI], 0.62 to 0.93; p 0.007), and the benefits are more significant when treatment is initiated before day 14 of ARDS (84 of 252 patients; 33%; vs 108 of 216 patients; 50%; RR, 0.71; 95% CI, 0.50 to 0.87; p 0.001). The mortality benefit with glucocorticoid treatment is greater than the benefit observed with low-tidal-volume ventilation (9%), 8 with number needed to treat to save one life of 6 for treatment initiated before day 14. Finally, the conclusion of the ARDS network trial 6 that methylprednisolone treatment increases mortality in patients randomized after day 14 is challenged by the large imbalances in baseline characteristics (control vs methylprednisolone) in this small subgroup of patients for age (45 13 years vs 52 24 years), male gender (56% vs 35%), trauma (20% vs 13%), pneumonia (28% vs 44%), serum creatinine (1.0 0.8 mg/dL vs 1.3 1.3 mg/dL), APACHE (acute physiology and chronic health evaluation) III score (79 22 vs 87 25), compliance (26 15 cm H2 Ov s 18 7c m H2O; p 0.02), and lung injury score (2.7 1.2 vs 3.7 0.87; p 0.001) [mean SD] that likely accounted for the uncharacteristically low mortality in the control group (8% vs 36%). These factors should be taken into consideration in analyzing the role of glucocorticoid treatment in ARDS, and should stimulate additional clinical investigation of this inexpensive and highly effective antiinflammatory therapy.
The Cutaneous Infiltrates of Leprosy
Authors: Wesley C. Van Voorhis, Gilla Kaplan, Euzenir Nunes Sarno, Marcus A. Horwitz, Ralph M. Steinman, William R. Levis, Nadia Nogueira, Laura S. Hair, Cerli Rocha Gattass, Bradley A. Arrick, Zanvil A. Cohn
Journal: New England Journal of Medicine (1982)

We report on the characteristics of cells in the cutaneous lesions and blood of 21 patients with lepromatous, tuberculoid, and intermediate forms of leprosy. A large proportion of the infiltrates in lepromatous lesions consist of macrophages heavily parasitized with Mycobacterium leprae. The T cells in the lesions are devoid of OKT4/Leu 3a-positive ("helper") cells and consist almost exclusively of OKT8/Leu 2a-positive ("suppressor") populations. In contrast, the tuberculoid infiltrates contain well-organized epithelioid and giant-cell granulomas and only remnants of bacilli, and the predominant T cell is from the OKT4/Leu 3a-positive subset. In both tuberculoid and lepromatous infiltrates, T cells and macrophages expressed HLA-DR antigen. No marked alteration in the distribution of blood T-cell phenotypes was noted. We conclude that there is a marked difference between T-cell subsets in lepromatous and tuberculoid infiltrates, which may influence the microbicidal activity of macrophages in the lesions.
Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Solid Tumors
Authors: Amita Patnaik, Glen J. Weiss, John E. Leonard, Drew Warren Rasco, Jasgit C. Sachdev, Terrence L. Fisher, Laurie A. Winter, Christine Reilly, Robert B. Parker, Danielle Mutz, Lisa Blaydorn, Anthony W. Tolcher, Maurice Zauderer, Ramesh K. Ramanathan
Journal: Clinical Cancer Research (2015)

Study objectives included evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of VX15/2503 in advanced solid tumor patients.Weekly i.v. doses were administered on a 28-day cycle. Safety, immunogenicity, PK, efficacy, T-cell membrane-associated SEMA4D (cSEMA4D) expression and saturation, soluble SEMA4D (sSEMA4D) serum levels, and serum biomarker levels were evaluated.Forty-two patients were enrolled into seven sequential cohorts and an expansion cohort (20 mg/kg). VX15/2503 was well tolerated. Treatment-related adverse events were primarily grade 1 or 2 and included nausea (14.3%) and fatigue (11.9%); arthralgia, decreased appetite, infusion-related reaction, and pyrexia were each 7.3%. One pancreatic cancer patient (15 mg/kg) experienced a Grade 3 dose-limiting toxicity; elevated γ-glutamyl transferase. Complete cSEMA4D saturation was generally observed at serum antibody concentrations ≥ 0.3 μg/mL, resulting in decreased cSEMA4D expression. Soluble SEMA4D levels increased with dose and infusion number. Neutralizing anti-VX15/2503 antibodies led to treatment discontinuation for 1 patient. VX15/2503 Cmax and AUC generally increased with dose and dose number. One patient (20 mg/kg) experienced a partial response, 19 patients (45.2%) exhibited SD for ≥ 8 weeks, and 8 (19%) had SD for ≥ 16 weeks. Subjects with elevated B/T lymphocytes exhibited longer progression-free survival.VX15/2503 was well tolerated and produced expected PD effects. The correlation between immune cell levels at baseline and progression-free survival is consistent with an immune-mediated mechanism of action. Future investigations will be in combination with immunomodulatory agents.
Immune Disregulation Of Hematopoiesis
Authors: K. Mangan
Journal: Annual Review of Medicine (1987)

In vitro coculture studies of normal T lymphocytes, natural killer (NK) cells, or monocytes with human hematopoietic progenitor cells (HPC) suggest a potential role for immune cells in the regulation ofhematopoiesis. In some patients with severe aplastic anemia or selective pure red cell, white cell, or megakaryocyte aplasia, activated T cells, NK cells, or mono­ cytes mediate marrow failure by suppressing growth of HPC. Immu­ nosuppressive agents such as corticosteroids, anti thymocyte globulin, cyclophosphamide ,