scholarly journals Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis

2007 ◽  
Vol 8 (3) ◽  
pp. 186-195 ◽  
Author(s):  
A Kindmark ◽  
A Jawaid ◽  
C G Harbron ◽  
B J Barratt ◽  
O F Bengtsson ◽  
...  
Keyword(s):  
Adverse Event ◽  
Clinical Signs ◽  
Immune Pathogenesis ◽  
Genome Wide ◽  
Hepatic Adverse Event

scholarly journals Genome-Wide Screen of Salmonella Genes Expressed during Infection in Pigs, Using In Vivo Expression Technology

2007 ◽  
Vol 73 (23) ◽  
pp. 7522-7530 ◽  
Author(s):  
Yanyan Huang ◽  
Christopher L. Leming ◽  
Mitsu Suyemoto ◽  
Craig Altier
Keyword(s):  
Genomic Library ◽  
Clinical Signs ◽  
Great Majority ◽  
Dna Fragments ◽  
Environmental Signals ◽  
Genome Wide ◽  
Serovar Typhimurium ◽  
Genes Encoding ◽  
Elevated Expression

ABSTRACT Pigs are a food-producing species that readily carry Salmonella but, in the great majority of cases, do not show clinical signs of disease. Little is known about the functions required by Salmonella to be maintained in pigs. We have devised a recombinase-based promoter-trapping strategy to identify genes with elevated expression during pig infection with Salmonella enterica serovar Typhimurium. A total of 55 clones with in vivo-induced promoters were selected from a genomic library of ∼10,000 random Salmonella DNA fragments fused to the recombinase cre, and the cloned DNA fragments were analyzed by sequencing. Thirty-one genes encoding proteins involved in bacterial adhesion and colonization (including bcfA, hscA, rffG, and yciR), virulence (metL), heat shock (hscA), and a sensor of a two-component regulator (hydH) were identified. Among the 55 clones, 19 were isolated from both the tonsils and the intestine, while 23 were identified only in the intestine and 13 only in tonsils. High temperature and increased osmolarity were identified as environmental signals that induced in vivo-expressed genes, suggesting possible signals for expression.

scholarly journals Genome-Wide Association Study Reveals Genetic Markers for Antimicrobial Resistance in Mycoplasma bovis

2021 ◽  
Author(s):  
Jade Bokma ◽  
Nick Vereecke ◽  
Hans Nauwynck ◽  
Freddy Haesebrouck ◽  
Sebastiaan Theuns ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Association Study ◽  
Genetic Markers ◽  
Genome Wide Association Study ◽  
Clinical Signs ◽  
Genome Wide Association ◽  
Effective Vaccine ◽  
Mycoplasma Bovis ◽  
Content Type ◽  
Genome Wide

Mycoplasma bovis is a leading cause of pneumonia but also causes other clinical signs in cattle. Since no effective vaccine is available, current M. bovis outbreak treatment relies primarily on the use of antimicrobials.

Zika Virus Changes Methylation of Genes Involved in Immune Response and Neural Development in Brazilian Babies Born With Congenital Microcephaly

2020 ◽  
Author(s):  
Denise Anderson ◽  
João I C F Neri ◽  
Cássio R M Souza ◽  
Joanna G Valverde ◽  
Josélio M G De Araújo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Neural Development ◽  
Zika Virus ◽  
Clinical Signs ◽  
Genome Wide ◽  
Immunity Genes ◽  
Congenital Microcephaly ◽  
Methylation Patterns ◽  
Methylation Profiling

Abstract The recent increase in babies born with brain and eye malformations in Brazil is associated with Zika virus (ZIKV) infection in utero. ZIKV alters host DNA methylation in vitro. Using genome-wide DNA methylation profiling we compared 18 babies born with congenital ZIKV microcephaly with 20 controls. We found ZIKV-associated alteration of host methylation patterns, notably at RABGAP1L which is important in brain development, at viral host immunity genes MX1 and ISG15, and in an epigenetic module containing the causal microcephaly gene MCPH1. Our data support the hypothesis that clinical signs of congenital ZIKV are associated with changes in DNA methylation.

Treatment with macitentan for pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD): real-world experience from the combined OPUS and OrPHeUS data sets

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V McLaughlin ◽  
K Chin ◽  
N.H Kim ◽  
M Flynn ◽  
R Ong ◽  
...  
Keyword(s):  
Adverse Event ◽  
Real World ◽  
Functional Class ◽  
Funding Source ◽  
Data Sets ◽  
Class Iii ◽  
Real World Data ◽  
Data Set ◽  
Number Of Patients ◽  
Hepatic Adverse Event

Abstract Introduction Restrictive inclusion criteria can exclude some CHD-PAH patients from clinical trials. The OPsumit® USers (OPUS) Registry and the OPsumit® Historical USers (OrPHeUS) data sets provide real-world data in PAH patients newly started on macitentan, including patients with CHD-PAH regardless of defect type. Purpose To describe the characteristics, safety and clinical outcomes of CHD-PAH patients newly treated with macitentan. Methods OPUS is a prospective, US, multicentre, observational drug registry ongoing since April 2014. OrPHeUS was a retrospective, US, multicentre chart review; observation period Oct 2013–Mar 2017. This analysis reports information on CHD-PAH patients in the combined OPUS/OrPHeUS data set, descriptively compared with idiopathic/heritable PAH (I/HPAH) patients. Results As of Sept 2019, there were 4268 PAH patients with follow-up data, of whom 264 (6%) had CHD-PAH and 2396 (56%) had I/HPAH. For CHD-PAH and I/HPAH patients respectively at macitentan initiation: median age (Q1, Q3) was 48 (36, 62) and 65 (53, 73) years; 199 (75%) and 1748 (73%) were female; 67/114 (59%) and 802/1301 (62%) were WHO functional class III/IV; median (Q1, Q3) 6-minute walk distances were 350 (274, 420) and 289 (195, 375) m for the 82 and 840 patients with measurements; median (Q1, Q3) time from PAH diagnosis to macitentan initiation was 37.3 (4.5, 113.1) and 7.4 (1.4, 38.3) months; and 99 (38%) and 1056 (44%) initiated macitentan as monotherapy. The number of patients with ≥1 hepatic adverse event (HAE) was similar for CHD-PAH and I/HPAH (22 [8%] and 184 [8%]), as were the adverse event (AE) profiles (collected from OPUS only). Exposure, discontinuations, outcomes and most common AEs are shown in the table. Conclusions In general, compared with I/HPAH patients, CHD-PAH patients were younger and a greater proportion had prevalent disease than I/HPAH patients. Safety and outcomes were similar between the groups. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Actelion Pharmaceuticals Ltd

scholarly journals Genome-wide transcriptomics identifies an early preclinical signature of prion infection

2020 ◽  
Author(s):  
Silvia Sorce ◽  
Mario Nuvolone ◽  
Giancarlo Russo ◽  
Andra Chincisan ◽  
Daniel Heinzer ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Prion Diseases ◽  
Clinical Signs ◽  
Mrna Abundance ◽  
Terminal Phase ◽  
Post Inoculation ◽  
Prion Infection ◽  
Molecular Events ◽  
Long Latency ◽  
Genome Wide

The clinical course of prion diseases is accurately predictable despite long latency periods, suggesting that prion pathogenesis is driven by precisely timed molecular events. We constructed a searchable genome-wide atlas of mRNA abundance, splicing and editing alterations during the course of disease in prion-inoculated mice. Prion infection induced transient changes in mRNA abundance and processing already at eight weeks post inoculation, well ahead of any neuropathological and clinical signs. In contrast, microglia-enriched genes displayed an increase simultaneous with the appearance of clinical symptoms, whereas neuronal-enriched transcripts remained unchanged until the very terminal stage of disease. This suggests that glial pathophysiology, rather than neuronal demise, represents the final driver of disease. The administration of young plasma attenuated the occurrence of early mRNA abundance alterations and delayed symptoms in the terminal phase of the disease. The early onset of prion-induced molecular changes might thus point to novel biomarkers and potential interventional targets.

A rapid method for the direct identification of paramyxovirus in canine CSF by ultracentrifugation and negative staining as a rule out for distemper

1990 ◽  
Vol 48 (3) ◽  
pp. 594-595
Author(s):  
W.L. Steffens ◽  
M.B. Ard ◽  
C.E. Greene ◽  
A. Jaggy
Keyword(s):  
Subacute Sclerosing Panencephalitis ◽  
Clinical Signs ◽  
Viral Disease ◽  
Etiologic Agent ◽  
Mucosal Inflammation ◽  
Worldwide Distribution ◽  
Negative Stain ◽  
Viral Particles ◽  
Systemic Manifestations ◽  
Rule Out

Canine distemper is a multisystemic contagious viral disease having a worldwide distribution, a high mortality rate, and significant central neurologic system (CNS) complications. In its systemic manifestations, it is often presumptively diagnosed on the basis of clinical signs and history. Few definitive antemortem diagnostic tests exist, and most are limited to the detection of viral antigen by immunofluorescence techniques on tissues or cytologic specimens or high immunoglobulin levels in CSF (cerebrospinal fluid). Diagnosis of CNS distemper is often unreliable due to the relatively low cell count in CSF (<50 cells/μl) and the binding of blocking immunoglobulins in CSF to cell surfaces. A more reliable and definitive test might be possible utilizing direct morphologic detection of the etiologic agent. Distemper is the canine equivalent of human measles, in that both involve a closely related member of the Paramyxoviridae, both produce mucosal inflammation, and may produce CNS complications. In humans, diagnosis of measles-induced subacute sclerosing panencephalitis is through negative stain identification of whole or incomplete viral particles in patient CSF.

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