tbuckley/cabot-search huggingface dataset:
Preservation of β-Cell Function in Autoantibody-Positive Youth With Diabetes
Authors: Carla J. Greenbaum, Andrea M. Anderson, Lawrence M. Dolan, Elizabeth J. Mayer-Davis, Dana Dabelea, Giuseppina Imperatore, Santica Marcovina, Catherine Pihoker
Journal: Diabetes Care (2009)

OBJECTIVE To determine the extent of β-cell function in youth with diabetes and GAD65 and/or IA2 autoantibodies. RESEARCH DESIGN AND METHODS Fasting C-peptide levels from 2,789 GAD65- and/or IA2 autoantibody-positive youth aged 1–23 years from the SEARCH for Diabetes in Youth study were used. Preserved β-cell function was defined on the basis of cut points derived from the Diabetes Control and Complications Trial (DCCT) (fasting C-peptide ≥0.23 ng/ml) and from the U.S. adolescent population of the National Health and Nutrition Examination Survey (NHANES) 5th percentile for fasting C-peptide (≥1.0 ng/ml). We compared the clinical characteristics between those with and without preserved β-cell function. RESULTS Within the first year of diagnosis, 82.9% of youth had a fasting C-peptide ≥0.23 ng/ml and 31.2% had values ≥1.0 ng/ml. Among those with ≥5 years of diabetes duration, 10.7% had preserved β-cell function based on the DCCT cutoff and 1.0% were above the 5th percentile of the NHANES population. CONCLUSIONS Within the 1st year of diagnosis, four of five youth with autoantibody-positive diabetes have clinically significant amounts of residual β-cell function and about one-third have fasting C-peptide levels above the 5th percentile of a healthy adolescent population. Even 5 years after diagnosis, 1 of 10 has fasting C-peptide above a clinically significant threshold. These findings have implications for clinical classification of youth with diabetes as well as clinical trials aimed to preserve β-cell function after diabetes onset.
Vascular endothelial growth factor-D transgenic mice show enhanced blood capillary density, improved postischemic muscle regeneration, and increased susceptibility to tumor formation
Authors: Anna-Mari Kärkkäinen, Antti Kotimaa, Jenni Huusko, Ivana Kholova, Suvi Elina Heinonen, Anna Stefanska, Marike Hinke Dijkstra, Hanna Purhonen, Eveliina Hämäläinen, Petri Ilmari Mäkinen, Mikko Petri Turunen, Seppo Ylä-Herttuala
Journal: Blood (2008)
Circulating MicroRNAs As Potential Biomarkers of Coronary Artery Disease
Authors: Riccardo Contu, Michael V.G. Latronico, Gianluigi Condorelli
Journal: Circulation Research (2010)

A therosclerotic coronary artery disease (CAD) continues to be an important socioeconomic problem and the leading cause of death in the Western world.Several cellular components, including endothelial, inflammatory, and smooth muscle cells of the arterial wall, participate in the generation of an atherosclerotic plaque, 1 the growth of which is responsible for a progressive narrowing of the lumen of the affected coronary vessel and the ensuing decrease in oxygenrich blood flow to downstream heart muscle, which may then be acutely or chronically damaged.Progression of CAD is highly variable and is driven by both environmental factors and genetic determinants.The genetic risk is thought to be attributable to an unfavorable combination of genetic variations in multiple genes that have not yet been completely characterized.However, major independent risk factors for CAD are known to include familiarity, high blood cholesterol levels, hypertension, smoking, diabetes, and obesity.Innovative early and reliable biomarkers and therapeutic targets for CAD would thus be acclaimed.MicroRNAs (also known as miRs or miRNAs) are approximately 20-to 25-nt-long noncoding RNAs that negatively regulate gene expression by binding to sites in the 3Ј untranslated region of targeted messenger RNAs. 2 These small RNAs have been found to be involved in almost every biological process, from cellular differentiation and proliferation 3,4 to cell death and apoptosis, 5,6 from synaptic plasticity 7 to immunity 8 and cardiovascular development 9 ; in addition, changes in miRNA levels and activity have been linked to human pathologies, including cancer 10 and cardiovascular diseases. 11,12ecently, miRNAs were found to be present in the circulating bloodstream, [13][14][15] together with other types of noncoding RNA, DNA, and mRNA. 16In fact, despite the high sensibility of all ribonucleic acids to RNase activity, it was discovered that plasma and serum miRNAs possess robust stability even after cycles of freezing/thawing. 14,15Moreover, circulating miRNAs were found to vary significantly during
Serum level of specific IgG antibody for aspergillus and its association with severity of asthma in asthmatic children
Authors: Ghamartaj Khanbabaee, Javad Enayat, Zahra Chavoshzadeh, Seyedahmad Tabatabaei, Nima Rezaei
Journal: European Respiratory Journal (2012)

Background: Aspergillosis is one of the frequent causes of exacerbation of asthma depending on the geographical regions. The specific serum IgG level for aspergillus is a major diagnostic criterion in aspergillosis.

Methods: Ninety six asthmatic patients, with mean age of 5.4±3.0 years who were referred to the asthma clinic of the Mofid Children's Hospital, were enrolled in this study. Serum specific IgG for aspergillus was measured and its association with severity of asthma was evaluated.

Results: Nineteen asthmatic patients (10 females and 9 males) had aspergillus IgG antibody. Among them, severe persistent asthma and moderate persistent asthma were detected in 5 and 13 cases, respectively, whereas only one patient suffered from mild persistent asthma. A total of 36.5% of the 96 patients had a history of atopy, while 26% had allergic rhinitis. There was an association between the severity of asthma and the presence of aspergillus IgG antibody. Moreover, the positivity for aspergillus IgG antibody was higher in older patients.

Conclusion: Our results indicated an association between aspergillus antibody level and severity of asthma. It could be recommended that the IgG titer for aspergillus is measured in pediatric patients with asthma, whereas co-morbidity of aspergillosis and asthma increases the risk of asthma exacerbation.
Measurement of IgE antibodies to shrimp tropomyosin is superior to skin prick testing with commercial extract and measurement of IgE to shrimp for predicting clinically relevant allergic reactions after shrimp ingestion
Authors: Ariana C. Yang, L. Karla Arruda, Ana Beatriz R. Santos, Michelle C.R. Barbosa, Martin D. Chapman, Clóvis E.S. Galvão, Jorge Kalil, Fábio F. Morato-Castro
Journal: Journal of Allergy and Clinical Immunology (2010)
A genetic polymorphism in the constant region of rabbit b4 kappa chains.
Authors: J A Sogn, T J Kindt
Journal: The Journal of Experimental Medicine (1976)

Amino acid sequence analysis of a b4 light chain from a rabbit homogeneous antistreptococcal antibody revealed the presence of two amino acid substitutions in the constant region not previously reported for these positions. These interchanges, consisting of serine for alanine at position 121 and leucine for glutamine at position 124, were also present in about 30% of the pooled b4 light chains isolated from pooled IgG from the rabbit (4539) that produced the homogeneous antibody. In addition, these interchanges (b4var) were found, always at the same levels, in varying percentages in nonimmune or early immune bleedings from related rabbits in this pedigreed family and could be traced for five generations. The inheritance pattern of b4var was consistent with autosomal codominant inheritance.
Gliadin-primed CD4+CD45RBlowCD25- T cells drive gluten-dependent small intestinal damage after adoptive transfer into lymphopenic mice
Authors: T. L. Freitag, S. Rietdijk, Y. Junker, Y. Popov, A. K. Bhan, C. P. Kelly, C. Terhorst, D. Schuppan
Journal: Gut (2009)

<h3>Background and aims:</h3> Coeliac disease is a common small intestinal inflammatory disorder that results from a breach of intestinal tolerance to dietary gluten proteins, driven by gluten-reactive effector T cells. We aimed to assess the pathogenic role of gluten-reactive T cells and to generate a model of gluten-induced enteropathy. <h3>Methods:</h3> CD4+CD25− T cell fractions were adoptively transferred into lymphopenic mice, leading to “baseline” small intestinal inflammation. <h3>Results:</h3> Rag1−/− recipients of gliadin-presensitised CD4+CD45RBlowCD25− T cells, but not CD4+CD45RBhigh naive T cells, gained less weight and suffered from more severe duodenitis when challenged with oral gluten than recipients on gluten-free diet, or recipients of control (ovalbumin)-presensitised T cells. This was accompanied by deterioration of mucosal histological features characteristic of coeliac disease, and increased Th1/Th17 cell polarisation in the duodenum and the periphery. Interestingly, reintroduction of a gluten-free diet led to weight gain, improvement of histological duodenitis, and a decrease in duodenal interferon γ and interleukin 17 transcripts. Moreover, B cell-competent nude recipients of gliadin-presensitised CD4+CD45RBlowCD25− T cells produced high levels of serum anti-gliadin immunoglobulin A (IgA) and IgG1/IgG2c only when challenged with oral gluten. <h3>Conclusions:</h3> CD4+ T cell immunity to gluten leads to a breach of oral gluten tolerance and small intestinal pathology in lymphopenic mice, similar to human coeliac disease. This model will be useful for the study of coeliac disease pathogenesis, and also for testing novel non-dietary therapies for coeliac disease.
Comparisons of characteristics and outcomes among women and men with acute myocardial infarction treated with thrombolytic therapy. GUSTO-I investigators
Authors: W D Weaver, H D White, R G Wilcox, P E Aylward, D Morris, A Guerci, E M Ohman, G I Barbash, A Betriu, Z Sadowski, E J Topol, R M Califf
Journal: JAMA (1996)

To compare baseline characteristics, complications, and treatment-specific outcomes of women and men with acute myocardial infarction treated with thrombolytic therapy.Randomized controlled trial.A total of 10315 women and 30706 men with acute myocardial infarction treated in 1081 hospitals in 15 countries as part of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I).One of four thrombolytic regimens: (1) streptokinase with subcutaneous heparin; (2) streptokinase with intravenous heparin; (3) streptokinase plus alteplase (tissue-type plasminogen activator) with intravenous heparin; or (4) accelerated alteplase with intravenous heparin.Mortality, stroke, and nonfatal complications during 30-day follow-up.Women were on average 7 years older than men and delayed 18 minutes (median) longer after symptom onset before presenting to the hospital. After adjustment for age, women more often had a history of diabetes, hypertension, and smoking than men. Time to treatment was significantly longer in women (1.2 vs 1.0 hours; P<.001). Women had more nonfatal complications after treatment, including shock (9% vs 5%; P<.001), congestive heart failure (22% vs 14%; P<.001), serious bleeding (15% vs 7%; P<.001), and reinfarction (5.1% vs 3.6%; P<.001). Women had twice as many total strokes as men (2.1% vs 1.2%; P<.001), secondary to their older age at presentation. The unadjusted mortality rate was twice as high in women as men (11.3% vs 5.5%; P<.001); the relative risk (RR) of death was greater among women than men after adjustment for differences in baseline characteristics (RR=1.15; 95% confidence interval, 1.0 to 1.31). Although women and men underwent angiography at similar rates, there were small but significant differences in their rates of revascularization procedures (angioplasty: 35% of women and 32% of men; bypass surgery: 7% of women and 9% of men; P<.001 for both). The higher rate of stroke in women after treatment with alteplase (2.0% vs 1.9% with streptokinase and intravenous heparin) was offset by a greater relative reduction in mortality (10.3% vs 11.1%).Women who received thrombolytic therapy for treatment of acute myocardial infarction were at greater risk for both fatal and nonfatal complications than men.
Nitric Oxide Modulates Chromatin Folding in Human Endothelial Cells via Protein Phosphatase 2A Activation and Class II Histone Deacetylases Nuclear Shuttling
Authors: Barbara Illi, Claudio Dello Russo, Claudia Colussi, Jessica Rosati, Michele Pallaoro, Francesco Spallotta, Dante Rotili, Sergio Valente, Gianluca Ragone, Fabio Martelli, Paolo Biglioli, Christian Steinkuhler, Paola Gallinari, Antonello Mai, Maurizio C. Capogrossi, Carlo Gaetano
Journal: Circulation Research (2007)

Nitric oxide (NO) modulates important endothelial cell (EC) functions and gene expression by a molecular mechanism which is still poorly characterized. Here we show that in human umbilical vein ECs (HUVECs) NO inhibited serum-induced histone acetylation and enhanced histone deacetylase (HDAC) activity. By immunofluorescence and Western blot analyses it was found that NO induced class II HDAC4 and 5 nuclear shuttling and that class II HDACs selective inhibitor MC1568 rescued serum-dependent histone acetylation above control level in NO-treated HUVECs. In contrast, class I HDACs inhibitor MS27–275 had no effect, indicating a specific role for class II HDACs in NO-dependent histone deacetylation. In addition, it was found that NO ability to induce HDAC4 and HDAC5 nuclear shuttling involved the activation of the protein phosphatase 2A (PP2A). In fact, HDAC4 nuclear translocation was impaired in ECs expressing small-t antigen and exposed to NO. Finally, in cells engineered to express a HDAC4-Flag fusion protein, NO induced the formation of a macromolecular complex including HDAC4, HDAC3, HDAC5, and an active PP2A. The present results show that NO-dependent PP2A activation plays a key role in class II HDACs nuclear translocation.
Cross-Priming of Naive Cd8 T Cells against Melanoma Antigens Using Dendritic Cells Loaded with Killed Allogeneic Melanoma Cells
Authors: Frederic Berard, Patrick Blanco, Jean Davoust, Eve-Marie Neidhart-Berard, Mahyar Nouri-Shirazi, Nicolas Taquet, Donata Rimoldi, Jean Charles Cerottini, Jacques Banchereau, A. Karolina Palucka
Journal: The Journal of Experimental Medicine (2000)

The goal of tumor immunotherapy is to elicit immune responses against autologous tumors. It would be highly desirable that such responses include multiple T cell clones against multiple tumor antigens. This could be obtained using the antigen presenting capacity of dendritic cells (DCs) and cross-priming. That is, one could load the DC with tumor lines of any human histocompatibility leukocyte antigen (HLA) type to elicit T cell responses against the autologous tumor. In this study, we show that human DCs derived from monocytes and loaded with killed melanoma cells prime naive CD45RA+CD27+CD8+ T cells against the four shared melanoma antigens: MAGE-3, gp100, tyrosinase, and MART-1. HLA-A201+ naive T cells primed by DCs loaded with HLA-A201− melanoma cells are able to kill several HLA-A201+ melanoma targets. Cytotoxic T lymphocyte priming towards melanoma antigens is also obtained with cells from metastatic melanoma patients. This demonstration of cross-priming against shared tumor antigens builds the basis for using allogeneic tumor cell lines to deliver tumor antigens to DCs for vaccination protocols.
Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders
Authors: Yaping Yang, Donna M. Muzny, Jeffrey G. Reid, Matthew N. Bainbridge, Alecia Willis, Patricia A. Ward, Alicia Braxton, Joke Beuten, Fan Xia, Zhiyv Niu, Matthew Hardison, Richard Person, Mir Reza Bekheirnia, Magalie S. Leduc, Amelia Kirby, Peter Pham, Jennifer Scull, Min Wang, Yan Ding, Sharon E. Plon, James R. Lupski, Arthur L. Beaudet, Richard A. Gibbs, Christine M. Eng
Journal: New England Journal of Medicine (2013)

Whole-exome sequencing is a diagnostic approach for the identification of molecular defects in patients with suspected genetic disorders.
Comparison of β-Blockers, Amiodarone Plus β-Blockers, or Sotalol for Prevention of Shocks From Implantable Cardioverter Defibrillators&lt;SUBTITLE&gt;The OPTIC Study: A Randomized Trial&lt;/SUBTITLE&gt;
Authors: Stuart J. Connolly
Journal: JAMA (2006)

Implantable cardioverter defibrillator (ICD) therapy is effective but is associated with high-voltage shocks that are painful.To determine whether amiodarone plus beta-blocker or sotalol are better than beta-blocker alone for prevention of ICD shocks.A randomized controlled trial with blinded adjudication of events of 412 patients from 39 outpatient ICD clinical centers located in Canada, Germany, United States, England, Sweden, and Austria, conducted from January 13, 2001, to September 28, 2004. Patients were eligible if they had received an ICD within 21 days for inducible or spontaneously occurring ventricular tachycardia or fibrillation.Patients were randomized to treatment for 1 year with amiodarone plus beta-blocker, sotalol alone, or beta-blocker alone.Primary outcome was ICD shock for any reason.Shocks occurred in 41 patients (38.5%) assigned to beta-blocker alone, 26 (24.3%) assigned to sotalol, and 12 (10.3%) assigned to amiodarone plus beta-blocker. A reduction in the risk of shock was observed with use of either amiodarone plus beta-blocker or sotalol vs beta-blocker alone (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.28-0.68; P<.001). Amiodarone plus beta-blocker significantly reduced the risk of shock compared with beta-blocker alone (HR, 0.27; 95% CI, 0.14-0.52; P<.001) and sotalol (HR, 0.43; 95% CI, 0.22-0.85; P = .02). There was a trend for sotalol to reduce shocks compared with beta-blocker alone (HR, 0.61; 95% CI, 0.37-1.01; P = .055). The rates of study drug discontinuation at 1 year were 18.2% for amiodarone, 23.5% for sotalol, and 5.3% for beta-blocker alone. Adverse pulmonary and thyroid events and symptomatic bradycardia were more common among patients randomized to amiodarone.Despite use of advanced ICD technology and treatment with a beta-blocker, shocks occur commonly in the first year after ICD implant. Amiodarone plus beta-blocker is effective for preventing these shocks and is more effective than sotalol but has an increased risk of drug-related adverse effects.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00257959.
Coagulation screen is more specific than the anticardiolipin antibody ELISA in defining a thrombotic subset of lupus patients.
Authors: R H Derksen, P Hasselaar, L Blokzijl, F H Gmelig Meyling, P G De Groot
Journal: Annals of the Rheumatic Diseases (1988)

In 111 lupus patients we compared the potential of the IgG and IgM anticardiolipin antibody (ACA) enzyme linked immunosorbent assay (ELISA) and four different lupus anticoagulant (LAC) assays (partial thromboplastin time (PTT) of a 1:1 mixture of patient and control plasma with phospholipids from animal (PTT-st) or human brain (PTT-HB); PTT with dilutions of human brain phospholipids (PL dilution); and kaolin clotting time of mixtures of patient and control plasma (KCT] to identify patients with thrombosis (26/111), fetal loss (19/46), and/or thrombocytopenia (11/106). The highest specificity for thrombosis (87%) was found with PTT-HB and PL dilution (sensitivity 65%, detection rate 61%); for fetal loss (93%) with PL dilution (sensitivity 47%; detection rate 82%), and for thrombocytopenia (83%) with KCT (sensitivity 82%; detection rate 36%). Compared with LAC assays, the sensitivity of ACA-ELISA was high (greater than or equal to 77%), but specificity (less than or equal to 51%) and detection rate (less than or equal to 52%) were low. So, a panel of three LAC assays (PTT-HB, PL dilution, and KCT) can identify lupus patients apparently at risk for thrombosis, fetal loss, and/or thrombocytopenia, whereas the ACA-ELISA is insufficiently specific.
Focused antibody response to influenza linked to antigenic drift
Authors: Kuan-Ying A. Huang, Pramila Rijal, Lisa Schimanski, Timothy J. Powell, Tzou-Yien Lin, John W. McCauley, Rodney S. Daniels, Alain R. Townsend
Journal: Journal of Clinical Investigation (2015)

The selective pressure that drives antigenic changes in influenza viruses is thought to originate from the human immune response. Here, we have characterized the B cell repertoire from a previously vaccinated donor whose serum had reduced neutralizing activity against the recently evolved clade 6B H1N1pdm09 viruses. While the response was markedly polyclonal, 88% of clones failed to recognize clade 6B viruses; however, the ability to neutralize A/USSR/90/1977 influenza, to which the donor would have been exposed in childhood, was retained. In vitro selection of virus variants with representative monoclonal antibodies revealed that a single amino acid replacement at residue K163 in the Sa antigenic site, which is characteristic of the clade 6B viruses, was responsible for resistance to neutralization by multiple monoclonal antibodies and the donor serum. The K163 residue lies in a part of a conserved surface that is common to the hemagglutinins of the 1977 and 2009 H1N1 viruses. Vaccination with the 2009 hemagglutinin induced an antibody response tightly focused on this common surface that is capable of selecting current antigenic drift variants in H1N1pdm09 influenza viruses. Moreover, amino acid replacement at K163 was not highlighted by standard ferret antisera. Human monoclonal antibodies may be a useful adjunct to ferret antisera for detecting antigenic drift in influenza viruses.
A Developmental Approach to the Borderline Patient
Authors: ELIZABETH R. ZETZEL
Journal: American Journal of Psychiatry (1971)

The treatment of the borderline patient involves considerable activity and definite structure on the part of the therapist, directed mainly toward helping the patient utilize a realistic doctor-patient relationship. Borderline patients are seldom capable of tolerating the painful affect integral to the emergence of regressive transference reactions. Despite this and other limitations, many borderline patients are capable of maintaining a high degree of adaptation, provided the therapist remains available to them in a limited manner for an indefinite period.
Nucleophosmin as a Candidate Prognostic Biomarker of Ewing's Sarcoma Revealed by Proteomics
Authors: Kazutaka Kikuta, Naobumi Tochigi, Tadakazu Shimoda, Hiroki Yabe, Hideo Morioka, Yoshiaki Toyama, Ako Hosono, Yasuo Beppu, Akira Kawai, Setsuo Hirohashi, Tadashi Kondo
Journal: Clinical Cancer Research (2009)

We aimed to identify novel prognostic biomarkers for Ewing's sarcoma by investigating the global protein expression profile of Ewing's sarcoma patients.We examined the proteomic profile of eight biopsy samples from Ewing's sarcoma patients using two-dimensional difference gel electrophoresis. Three patients were alive and continuously disease-free over 3 years after the initial diagnosis (good prognosis group) and five had died of the disease within 2 years of the initial diagnosis (poor prognosis group).The protein expression profiles produced using two-dimensional difference gel electrophoresis consisted of 2,364 protein spots, among which we identified 66 protein spots whose intensity showed >2-fold difference between the two patient groups. Mass spectrometric protein identification showed that the 66 spots corresponded to 53 distinct gene products. Pathway analysis revealed that 31 of 53 proteins, including nucleophosmin, were significantly related to bone tissue neoplasms (P < 0.000001). The prognostic performance of nucleophosmin was evaluated immunohistochemically on an additional 34 Ewing's sarcoma cases. Univariate and multivariate analyses revealed that nucleophosmin expression significantly correlated with overall survival (P < 0.01).These results establish nucleophosmin as a candidate of independent prognostic marker for Ewing's sarcoma patients. Measuring nucleophosmin in biopsy samples before treatment may contribute to the effective management of Ewing's sarcoma.