tbuckley/cabot-search huggingface dataset:
OBSERVATIONS ON ATTEMPTS TO PRODUCE ACUTE DISSEMINATED ENCEPHALOMYELITIS IN MONKEYS
Authors: Thomas M. Rivers, D. H. Sprunt, G. P. Berry
Journal: The Journal of Experimental Medicine (1933)

No evidence was found to support the idea that vaccine virus placed in the cisterna magna is capable of producing an acute disseminated encephalomyelitis with perivascular demyelination either in normal or in partially immune monkeys. A testicular extract (Reynals' factor) did not induce vaccine virus to cause an acute disseminated encephalomyelitis in monkeys. Repeated intramuscular injections of brain extracts and brain emulsions into eight monkeys were followed in two instances by an inflammatory reaction, accompanied by demyelination, in the central nervous system. The exact relation of the injections to the disease of the nervous system is not clear. The combined action of vaccine virus and an emulsion of fresh rabbit brain did not lead to the production of an acute disseminated encephalomyelitis in monkeys that had received repeated intramuscular injections of emulsions and alcohol-ether extracts of normal rabbit brains.
hTERT Inhibition Triggers Epstein–Barr Virus Lytic Cycle and Apoptosis in Immortalized and Transformed B Cells: A Basis for New Therapies
Authors: Silvia Giunco, Riccardo Dolcetti, Sonia Keppel, Andrea Celeghin, Stefano Indraccolo, Jessica Dal Col, Katy Mastorci, Anita De Rossi
Journal: Clinical Cancer Research (2013)

Induction of viral lytic cycle, which induces death of host cells, may constitute a useful adjunct to current therapeutic regimens for Epstein-Barr virus (EBV)-driven malignancies. Human telomerase reverse transcriptase (hTERT), essential for the oncogenic process, may modulate the switch from latent to lytic infection. The possible therapeutic role of hTERT inhibition combined with antiviral drugs was investigated.EBV-negative BL41 and convertant EBV-positive BL41/B95.8 Burkitt's lymphoma cell lines and lymphoblastoid cell lines (LCL) were infected with retroviral vector encoding short hairpin RNA (shRNA) anti-hTERT and cultured with or without the prodrug ganciclovir. The effects on EBV lytic replication, cell proliferation, and apoptosis were characterized.hTERT silencing by shRNA induced the expression of BZLF1, EA-D, and gp350 EBV lytic proteins and triggered a complete lytic cycle. This effect was associated with downregulation of BATF, a negative regulator of BZLF1 transcription. hTERT silencing also resulted in antiproliferative and proapoptotic effects. In particular, hTERT inhibition induced an accumulation of cells in the S-phase, an effect likely due to the dephosphorylation of 4E-BP1, an AKT1-dependent substrate, which results in a decreased availability of proteins needed for cell-cycle progression. Besides inducing cell death through activation of complete EBV lytic replication, hTERT inhibition triggered AKT1/FOXO3/NOXA-dependent apoptosis in EBV-positive and -negative Burkitt's lymphoma cells. Finally, ganciclovir enhanced the apoptotic effect induced by hTERT inhibition in EBV-positive Burkitt's lymphomas and LCLs.These results suggest that combination of antiviral drugs with strategies able to inhibit hTERT expression may result in therapeutically relevant effects in patients with EBV-related malignancies.
Altered Na <sup>+</sup> Channels Promote Pause-Induced Spontaneous Diastolic Activity in Long QT Syndrome Type 3 Myocytes
Authors: Sandra Fredj, Nicolas Lindegger, Kevin J. Sampson, Peter Carmeliet, Robert S. Kass
Journal: Circulation Research (2006)

Long QT syndrome (LQTS) type 3 (LQT3), typified by the DeltaKPQ mutation (LQT3 mutation in which amino acid residues 1505 to 1507 [KPQ] are deleted), is caused by increased sodium entry during the action potential plateau resulting from mutation-altered inactivation of the Na(v)1.5 channel. Although rare, LQT3 is the most lethal of common LQTS variants. Here we tested the hypothesis that cellular electrical dysfunction, caused not only by action potential prolongation but also by mutation-altered Na(+) entry, distinguishes LQT3 from other LQTS variants and may contribute to its distinct lethality. We compared cellular electrical activity in myocytes isolated from mice heterozygous for the DeltaKPQ mutation (DeltaKPQ) and myocytes from wild-type littermates. Current-clamp pause protocols induced rate-dependent spontaneous diastolic activity (delayed after depolarizations) in 6 of 7 DeltaKPQ, but no wild-type, myocytes (n=11) tested. Voltage-clamp pause protocols that independently control depolarization duration and interpulse interval identified a distinct contribution of both depolarization duration and mutant Na(+) channel activity to the generation of Ca(i)(2+)-dependent diastolic transient inward current. This was found at rates and depolarization durations relevant both to the mouse model and to LQT3 patients. Flecainide, which preferentially inhibits mutation-altered late Na(+) current and is used to treat LQT3 patients, suppresses transient inward current formation in voltage-clamped DeltaKPQ myocytes. Our results demonstrate a marked contribution of mutation-altered Na(+) entry to the incidence of pause-dependent spontaneous diastolic activity in DeltaKPQ myocytes and suggest that altered Na(+) entry may contribute to the elevated lethality of LQT3 versus other LQTS variants.
Interspecies spleen-myeloma hybrid producing monoclonal antibodies against mouse lymphocyte surface glycoprotein, T200.
Authors: I S Trowbridge
Journal: The Journal of Experimental Medicine (1978)

A cell hybrid has been selected from fusion of a mouse myeloma and rat spleen cells immunized against mouse lymphoma cells that produces monoclonal antibody against the mouse lymphocyte surface glycoprotein, T200. Antibody binding assays employing the monoclonal antibody show that there are about 50,000-100,000 molecules of T200 glycoprotein on mouse thymocytes and that similar antigens are present on spleen and bone marrow but not detected on nonlymphoid tissues. Examination of the labeled molecules precipitated from detergent extracts of spleen cells and thymocytes iodinated by the lactoperoxidase technique by SDS-PAGE confirm that there are structural differences between the antigens found on B and T lymphocytes. The B-cell glycoprotein consists of at least one component of apparent mol wt 220,000 on SDS-PAGE, while the T-cell glycoprotein has an apparent mol wt of about 190,000.
Capsule Endoscopy: From Current Achievements to Open Challenges
Authors: Gastone Ciuti, Arianna Menciassi, Paolo Dario
Journal: IEEE Reviews in Biomedical Engineering (2011)

Wireless capsule endoscopy (WCE) can be considered an example of disruptive technology since it represents an appealing alternative to traditional diagnostic techniques. This technology enables inspection of the digestive system without discomfort or need for sedation, thus preventing the risks of conventional endoscopy, and has the potential of encouraging patients to undergo gastrointestinal (GI) tract examinations. However, currently available clinical products are passive devices whose locomotion is driven by natural peristalsis, with the drawback of failing to capture the images of important GI tract regions, since the doctor is unable to control the capsule's motion and orientation. To address these limitations, many research groups are working to develop active locomotion devices that allow capsule endoscopy to be performed in a totally controlled manner. This would enable the doctor to steer the capsule towards interesting pathological areas and to accomplish medical tasks. This review presents a research update on WCE and describes the state of the art of the basic modules of current swallowable devices, together with a perspective on WCE potential for screening, diagnostic, and therapeutic endoscopic procedures.
Preclinical development of an adjuvant-free peptide vaccine with activity against CMV pp65 in HLA transgenic mice
Authors: Corinna La Rosa, Zhongde Wang, John C. Brewer, Simon F. Lacey, Maria C. Villacres, Rahul Sharan, Radhika Krishnan, Matthew Crooks, Susan Markel, Rebecca Maas, Don J. Diamond
Journal: Blood (2002)
Integrative functional genomics identifies RINT1 as a novel GBM oncogene
Authors: Steven N. Quayle, Milan G. Chheda, Sachet A. Shukla, Ruprecht Wiedemeyer, Pablo Tamayo, Robert W. Dewan, Li Zhuang, Emmet Huang-Hobbs, Sam Haidar, Yonghong Xiao, Keith L. Ligon, William C. Hahn, Lynda Chin
Journal: Neuro-Oncology (2012)

Large-scale cancer genomics efforts are identifying hundreds of somatic genomic alterations in glioblastoma (GBM). Distinguishing between active driver and neutral passenger alterations requires functional assessment of each gene; therefore, integrating biological weight of evidence with statistical significance for each genomic alteration will enable better prioritization for downstream studies. Here, we demonstrate the feasibility and potential of in vitro functional genomic screens to rapidly and systematically prioritize high-probability candidate genes for in vivo validation. Integration of low-complexity gain- and loss-of-function screens designed on the basis of genomic data identified 6 candidate GBM oncogenes, and RINT1 was validated as a novel GBM oncogene based on its ability to confer tumorigenicity to primary nontransformed murine astrocytes in vivo. Cancer genomics-guided low-complexity genomic screens can quickly provide a functional filter to prioritize high-value targets for further downstream mechanistic and translational studies.
The Genetic Basis of Peripheral Arterial Disease
Authors: Iftikhar J. Kullo, Nicholas J. Leeper
Journal: Circulation Research (2015)

Several risk factors for atherosclerotic peripheral arterial disease (PAD), such as dyslipidemia, diabetes mellitus, and hypertension, are heritable. However, predisposition to PAD may be influenced by genetic variants acting independently of these risk factors. Identification of such genetic variants will provide insights into underlying pathophysiologic mechanisms and facilitate the development of novel diagnostic and therapeutic approaches. In contrast to coronary heart disease, relatively few genetic variants that influence susceptibility to PAD have been discovered. This may be, in part, because of greater clinical and genetic heterogeneity in PAD. In this review, we (1) provide an update on the current state of knowledge about the genetic basis of PAD, including results of family studies and candidate gene, linkage as well as genome-wide association studies; (2) highlight the challenges in investigating the genetic basis of PAD and possible strategies to overcome these challenges; and (3) discuss the potential of genome sequencing, RNA sequencing, differential gene expression, epigenetic profiling, and systems biology in increasing our understanding of the molecular genetics of PAD.
Assessment of asthma control by children and parents
Authors: Sandra Voorend-van Bergen, Hein Brackel, Daan Caudri, Johan de Jongste, Mariëlle Pijnenburg
Journal: European Respiratory Journal (2012)

Recent guidelines place a strong emphasis on monitoring asthma control and adjusting treatment accordingly [1].Several tools are available to assess asthma control, including the asthma control test and childhood asthma control test (C-ACT).These tests were developed to detect uncontrolled asthma and are widely used in research and patient care [2,3].
Recurrence of spondylarthropathy among first-degree relatives of patients: a systematic cross-sectional study
Authors: E Dernis, R Said-Nahal, M-A D’Agostino, P Aegerter, M Dougados, M Breban
Journal: Annals of the Rheumatic Diseases (2008)

Objective: To examine the recurrence of manifestations belonging to the spectrum of spondylarthropathy (SpA) in first-degree relatives of patients with SpA, and to estimate the recurrence risk ratio. Methods: Parents and siblings of consecutive SpA probands have been thoroughly investigated, including clinical data collection, pelvic x ray and human leukocyte antigen (HLA)-B27 status determination. The diagnosis of SpA was made according to European Spondylarthropathy Study Group and/or the Amor criteria. The recurrence risk ratio λ 1 , which gives an estimate of the weight of genetic factors, was calculated as the ratio of the recurrence risk of SpA in first-degree relatives compared with the population prevalence of SpA. The λ non-HLA was obtained by similar calculations restricted to HLA-B27+ individuals. Results: Most manifestations of SpA were more frequent among the 157 HLA-B27+ relatives of 83 probands than among their 111 HLA-B27- relatives. A diagnosis of SpA was made in 50 relatives of 31 (37%) probands. Recurrence was very similar between parents and siblings, without gender difference, resulting in overall recurrence risk of 12% in first-degree relatives and of 22.7% in HLA-B27+ relatives. The λ 1 value was 40 and the λ non-HLA value was 6.5, very close to the λ HLA value of 6.25 estimated from linkage study in SpA. Conclusions: A similar recurrence risk of SpA was observed between parents and siblings, consistent with a model of inheritance with no dominance variance and without sex influence. The weight of the non-HLA genetic component was equivalent to that estimated for the HLA locus, and fitted a model of multiplicative interaction between HLA and non-HLA genetic components.
Substance Use in Adolescence and Psychosis: Clarifying the Relationship
Authors: Emma Barkus, Robin M. Murray
Journal: Annual Review of Clinical Psychology (2010)

Adolescence is a time of exploration of the self, and this exploration may involve the use of alcohol and drugs. Sadly, for some, adolescence also marks the first signs of a psychosis. The temporal proximity between the onset of substance use and of psychosis has been the cause of much debate. Here we review the association of alcohol, cannabis, stimulants, and other drugs with psychosis, and we conclude that the use of cannabis and the amphetamines significantly contributes to the risk of psychosis.
Response to Comment on Nordwall et al. Impact of HbA1c, Followed From Onset of Type 1 Diabetes, on the Development of Severe Retinopathy and Nephropathy: The VISS Study (Vascular Diabetic Complications in Southeast Sweden). Diabetes Care 2015;38:308–315
Authors: Maria Nordwall, Mariann Abrahamsson, Meryl Dhir, Mats Fredrikson, Johnny Ludvigsson, Hans J. Arnqvist
Journal: Diabetes Care (2015)

We thank Dr. Takahara (1) for the comment on our recent article exploring the impact of HbA1c, followed from diabetes onset, on the development of severe microvascular complications (2). As suggested, we have validated our results with Cox hazards analysis with severe microvascular events, i.e., laser-treated proliferative retinopathy and macroalbuminuria …
Distinct patterns of SSR distribution in the Arabidopsis thaliana and rice genomes.
Authors: Mark J Lawson, Liqing Zhang
Journal: Genome biology (2006)

Abstract Background Simple sequence repeats (SSRs) in DNA have been traditionally thought of as functionally unimportant and have been studied mainly as genetic markers. A recent handful of studies have shown, however, that SSRs in different positions of a gene can play important roles in determining protein function, genetic development, and regulation of gene expression. We have performed a detailed comparative study of the distribution of SSRs in the sequenced genomes of Arabidopsis thaliana and rice. Results SSRs in different genic regions - 5'untranslated region (UTR), 3'UTR, exon, and intron - show distinct patterns of distribution both within and between the two genomes. Especially notable is the much higher density of SSRs in 5'UTRs compared to the other regions and a strong affinity towards trinucleotide repeats in these regions for both rice and Arabidopsis . On a genomic level, mononucleotide repeats are the most prevalent type of SSRs in Arabidopsis and trinucleotide repeats are the most prevalent type in rice. Both plants have the same most common mononucleotide (A/T) and dinucleotide (AT and AG) repeats, but have little in common for the other types of repeats. Conclusion Our work provides insight into the evolution and distribution of SSRs in the two sequenced model plant genomes of monocots and dicots. Our analyses reveal that the distributions of SSRs appear highly non-random and vary a great deal in different regions of the genes in the genomes.
ALX-chemy: adding spice to the inflammatory soup of atherosclerosis
Authors: Peter Libby
Journal: Cardiovascular Research (2014)

This editorial refers to ‘The role of the FPR2/ALX receptor in atherosclerosis development and plaque stability’ by M.H. Petri et al. , pp. 65–74, this issue. 

Nature often presents complexities, for example the formyl peptide receptor (FPR) 2/ALX that curiously can mediate either pro-inflammatory or pro-resolution of inflammation responses depending on the ligand it encounters. Formyl peptides originate from bacteria. The formyl peptide receptor may not only respond to products derived from pathogenic organisms but also from commensals in the intestinal and other endogenous microbiomes, whose contribution to atherosclerosis has garnered considerable recent interest.

The ALX designation derives from the response of this family of receptors to lipoxin A4. This receptor binds other ligands relevant to atherosclerosis, including serum amyloid A (SAA). Given this variety of agonists, the role of FPR2/ALX in atherogenesis has proved confusing. The study by Petri et al. provides a comprehensive re-evaluation of the role of FPR2/ALX in atherosclerosis.1 In a thorough series of investigations, these authors have established the presence of this receptor in specimens of human atherosclerosis, documenting its expression presence on inflammatory cells and intrinsic vascular wall cells in plaques but not in normal arteries. The messenger RNA encoding FPR2/ALX in the retrieved carotid endarterectomy specimens correlated with symptomatic cerebral ischaemia. Joined with these observations on human plaques, the authors showed delayed atherosclerosis and fewer inflammatory cells in LDL …
Semaphorin 3A overcomes cancer hypoxia and metastatic dissemination induced by antiangiogenic treatment in mice
Authors: Federica Maione, Stefania Capano, Donatella Regano, Lorena Zentilin, Mauro Giacca, Oriol Casanovas, Federico Bussolino, Guido Serini, Enrico Giraudo
Journal: Journal of Clinical Investigation (2012)

Cancer development, progression, and metastasis are highly dependent on angiogenesis. The use of antiangiogenic drugs has been proposed as a novel strategy to interfere with tumor growth, but cancer cells respond by developing strategies to escape these treatments. In particular, animal models show that antiangiogenic drugs currently used in clinical settings reduce tumor tissue oxygenation and trigger molecular events that foster cancer resistance to therapy. Here, we show that semaphorin 3A (Sema3A) expression overcomes the proinvasive and prometastatic resistance observed upon angiogenesis reduction by the small-molecule tyrosine inhibitor sunitinib in both pancreatic neuroendocrine tumors (PNETs) in RIP-Tag2 mice and cervical carcinomas in HPV16/E2 mice. By improving cancer tissue oxygenation and extending the normalization window, Sema3A counteracted sunitinib-induced activation of HIF-1α, Met tyrosine kinase receptor, epithelial-mesenchymal transition (EMT), and other hypoxia-dependent signaling pathways. Sema3A also reduced tumor hypoxia and halted cancer dissemination induced by DC101, a specific inhibitor of the VEGF pathway. As a result, reexpressing Sema3A in cancer cells converts metastatic PNETs and cervical carcinomas into benign lesions. We therefore suggest that this strategy could be developed to safely harnesses the therapeutic potential of the antiangiogenic treatment.
Peer-Led Diabetes Education Programs in High-Risk Mexican Americans Improve Glycemic Control Compared With Standard Approaches
Authors: Athena Philis-Tsimikas, Adelaide Fortmann, Leticia Lleva-Ocana, Chris Walker, Linda C. Gallo
Journal: Diabetes Care (2011)

OBJECTIVE To evaluate the effect of a culturally sensitive diabetes self-management education program that uses a low-cost, peer-educator format (Project Dulce) on glucose control and metabolic parameters in low-income Mexican Americans with type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 207 Mexican-American patients recruited from federally funded community health centers in San Diego County with HbA1c &amp;gt;8% were randomly assigned to the Project Dulce peer intervention or continuation of standard diabetes care. The primary outcome of interest was HbA1c. RESULTS The majority of subjects were born in Mexico, were female, were middle-aged, had less than an eighth-grade education, and had high baseline HbA1c levels. Significant time-by-group interaction effects for HbA1c (P = 0.02) and diastolic blood pressure (P = 0.04) indicated that the Project Dulce group exhibited greater improvement (i.e., decreases) across time. Within-group analyses showed that the intervention group exhibited significant improvements from baseline to month 4 in absolute levels of HbA1c (−1.7%, P = 0.001) and HDL cholesterol (+1.4 mg/dL, P = 0.01) and from baseline to month 10 in absolute levels of HbA1c (−1.5%, P = 0.01), total cholesterol (−7.2 mg/dL, P = 0.04), HDL cholesterol (+1.6 mg/dL, P = 0.01), and LDL cholesterol (−8.1 mg/dL, P = 0.02). No significant changes were noted in the control group. CONCLUSIONS This randomized trial, using the Project Dulce model of culturally sensitive, peer-led education, demonstrates improvement in glucose and metabolic control and suggests that this low-cost approach to self-management education for high-risk diabetic populations is effective.
Type 1 Diabetes Is Associated With Increased Cyclooxygenase- and Cytokine-Mediated Inflammation
Authors: Samar Basu, Anders Larsson, Johan Vessby, Bengt Vessby, Christian Berne
Journal: Diabetes Care (2005)

OBJECTIVE—The extent of involvement of cyclooxygenase (COX)-mediated inflammation in type 1 diabetes is unknown, and the association between the COX- and cytokine-mediated inflammatory responses in type 1 diabetes is not fully understood. RESEARCH DESIGN AND METHODS—Plasma high-sensitivity C-reactive protein (CRP), 24-h urinary and plasma 15-keto-dihydro-prostaglandin F2α (a metabolite of prostaglandin F2α [PGF2α] and an indicator of COX-mediated inflammation), serum amyloid protein A (SAA), and interleukin (IL)-6 (indicators of inflammation) were measured in 38 subjects with type 1 diabetes and 41 healthy age- and sex-matched control subjects. RESULTS—The inflammatory indicators (urinary 15-keto-dihydro-PGF2α, P &amp;lt; 0.01; IL-6, P &amp;lt; 0.04) were increased in men with diabetes. CRP and SAA did not show any significant difference between the diabetic and the control subjects. Urinary levels of 15-keto-dihydro-PGF2α correlated with the degree of glycemic control, HbA1c (r = 0.42, P &amp;lt; 0.0005). No correlation was found between the duration of diabetes and the inflammatory biomarkers or metabolic measurements. CONCLUSIONS—These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF2α and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.