Institution
University of Iowa
Education•Iowa City, Iowa, United States•
About: University of Iowa is a education organization based out in Iowa City, Iowa, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 49229 authors who have published 109171 publications receiving 5021465 citations. The organization is also known as: UI & The University of Iowa.
Papers published on a yearly basis
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UCL Institute of Neurology1, French Institute of Health and Medical Research2, University of British Columbia3, Leiden University4, CHDI Foundation5, University of Ulm6, University of London7, University of Iowa8, Central Manchester University Hospitals NHS Foundation Trust9, University of Manchester10, University of Münster11, Monash University12
TL;DR: In early HD, imaging, quantitative motor, and cognitive measures were predictive of decline in total functional capacity and tracked longitudinal change, and neuropsychiatric changes consistent with frontostriatal pathological abnormalities were associated with this loss of functional capacity.
Abstract: Summary Background TRACK-HD is a multinational prospective observational study of Huntington's disease (HD) that examines clinical and biological findings of disease progression in individuals with premanifest HD (preHD) and early-stage HD. We aimed to describe phenotypic changes in these participants over 36 months and identify baseline predictors of progression. Methods Individuals without HD but carrying the mutant huntingtin gene (classed as preHD-A if ≥10·8 years and preHD-B if Findings At baseline, 366 participants were enrolled between Jan 17, and Aug 26, 2008, and of these 298 completed 36-month follow-up: 97 controls, 58 participants with preHD-A, 46 with preHD-B, 66 with HD1, and 31 with HD2. In the preHD-B group, several quantitative motor and cognitive tasks showed significantly increased rates of decline at 36 months, compared with controls, whereas few had at 24 months. Of the cognitive measures, the symbol digit modality test was especially sensitive (adjusted mean loss 4·11 points [95% CI 1·49–6·73] greater than controls; p=0·003). Among psychiatric indicators, apathy ratings specifically showed significant increases (0·34 points [95% CI 0·02–0·66] greater than controls; p=0·038). There was little evidence of reliable change in non-imaging measures in the preHD-A group, with the exception of the speeded tapping inter-tap interval (0·01 s [95% CI 0·01–0·02] longer than controls; p=0·0001). Several baseline imaging, quantitative motor, and cognitive measures had prognostic value, independent of age and CAG repeat length, for predicting subsequent clinical diagnosis in preHD. Of these, grey-matter volume and inter-tap interval were particularly sensitive (p=0·013 and 0·002, respectively). Longitudinal change in these two measures was also greater in participants with preHD who received a diagnosis of HD during the study compared with those who did not, after controlling for CAG repeat length and age-related risk (p=0·006 and 0·0003, respectively). In early HD, imaging, quantitative motor, and cognitive measures were predictive of decline in total functional capacity and tracked longitudinal change; also, neuropsychiatric changes consistent with frontostriatal pathological abnormalities were associated with this loss of functional capacity (problem behaviours assessment composite behaviour score p Interpretation We have shown changes in several outcome measures in individuals with preHD over 36 months. These findings further our understanding of HD progression and have implications for clinical trial design. Funding CHDI Foundation.
692 citations
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TL;DR: It is shown that RNAi directed against mutant human htt reduced htt mRNA and protein expression in cell culture and in HD mouse brain, and improved behavioral and neuropathological abnormalities associated with HD.
Abstract: Huntington's disease (HD) is a fatal, dominant neurogenetic disorder. HD results from polyglutamine repeat expansion (CAG codon, Q) in exon 1 of HD, conferring a toxic gain of function on the protein huntingtin (htt). Currently, no preventative treatment exists for HD. RNA interference (RNAi) has emerged as a potential therapeutic tool for treating dominant diseases by directly reducing disease gene expression. Here, we show that RNAi directed against mutant human htt reduced htt mRNA and protein expression in cell culture and in HD mouse brain. Importantly, htt gene silencing improved behavioral and neuropathological abnormalities associated with HD. Our data provide support for the further development of RNAi for HD therapy.
691 citations
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TL;DR: These prospective findings indicate that CRP and IL-6 independently predict vascular events among apparently healthy postmenopausal women and that HRT increases CRP.
Abstract: ContextPostmenopausal hormone replacement therapy (HRT) has been shown to elevate
C-reactive protein (CRP) levels. Several inflammatory biomarkers, including
CRP, are associated with increased cardiovascular risk. However, whether the
effect of HRT on CRP represents a clinical hazard is unknown.ObjectivesTo assess the association between baseline levels of CRP and interleukin
6 (IL-6) and incident coronary heart disease (CHD) and to examine the relationship
between baseline use of HRT, CRP, and IL-6 levels as they relate to subsequent
vascular risk.Design, Setting, and ParticipantsProspective, nested case-control study of postmenopausal women, forming
part of the Women's Health Initiative, a large, nationwide, observational
study. Among 75 343 women with no history of cardiovascular disease or
cancer, 304 women who developed incident CHD were defined as cases and matched
by age, smoking status, ethnicity, and follow-up time with 304 study participants
who remained event free during a median observation period of 2.9 years.Main Outcome MeasureIncidence of first myocardial infarction or death from CHD.ResultsMedian baseline levels of CRP (0.33 vs 0.25 mg/dL; interquartile range
[IQR], 0.14-0.71 vs 0.10-0.47; P<.001) and IL-6
(1.81 vs 1.47 pg/mL; IQR, 1.30-2.75 vs 1.05-2.15; P<.001)
were significantly higher among cases compared with controls. In matched analyses,
the odds ratio (OR) for incident CHD in the highest vs lowest quartile was
2.3 for CRP (95% confidence interval [CI], 1.4-3.7; P
for trend = .002) and 3.3 for IL-6 (95% CI, 2.0-5.5; P
for trend <.001). After additional adjustment for lipid and nonlipid risk
factors, both inflammatory markers were significantly associated with a 2-fold
increase in odds for CHD events. As anticipated, current use of HRT was associated
with significantly elevated median CRP levels. However, there was no association
between HRT and IL-6. In analyses comparing individuals with comparable baseline
levels of either CRP or IL-6, those taking or not taking HRT had similar CHD
ORs. In analyses stratified by HRT, we observed a positively graded relationship
between plasma CRP levels and the OR for CHD among both users and nonusers
of HRT across the full spectrum of baseline CRP.ConclusionsThese prospective findings indicate that CRP and IL-6 independently
predict vascular events among apparently healthy postmenopausal women and
that HRT increases CRP. However, use or nonuse of HRT had less importance
as a predictor of cardiovascular risk than did baseline levels of either CRP
or IL-6.
691 citations
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TL;DR: The importance and complexity of myeloperoxidase‐mediated events illustrate a collaboration of anti‐microbial responses that are endogenous to the neutrophil, whereas the synergy between the phagocyte NADPH and plasma‐derived group IIA phospholipase A2 exemplifies the collective effects of the neutophil with an exogenous factor to achieve degradation of ingested staphylococci.
Abstract: Neutrophils constitute the dominant cell in the circulation that mediates the earliest innate immune human responses to infection. The morbidity and mortality from infection rise dramatically in patients with quantitative or qualitative neutrophil defects, providing clinical confirmation of the important role of normal neutrophils for human health. Neutrophil-dependent anti-microbial activity against ingested microbes represents the collaboration of multiple agents, including those prefabricated during granulocyte development in the bone marrow and those generated de novo following neutrophil activation. Furthermore, neutrophils cooperate with extracellular agents as well as other immune cells to optimally kill and degrade invading microbes. This brief review focuses attention on two examples of the integrated nature of neutrophil-mediated anti-microbial action within the phagosome. The importance and complexity of myeloperoxidase-mediated events illustrate a collaboration of anti-microbial responses that are endogenous to the neutrophil, whereas the synergy between the phagocyte NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and plasma-derived group IIA phospholipase A(2) exemplifies the collective effects of the neutrophil with an exogenous factor to achieve degradation of ingested staphylococci.
690 citations
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TL;DR: Upon intracerebellar injection, recombinant adeno-associated virus vectors expressing short hairpin RNAs profoundly improved motor coordination, restored cerebellar morphology and resolved characteristic ataxin-1 inclusions in Purkinje cells of SCA1 mice, demonstrating in vivo the potential use of RNAi as therapy for dominant neurodegenerative disease.
Abstract: The dominant polyglutamine expansion diseases, which include spinocerebellar ataxia type 1 (SCA1) and Huntington disease, are progressive, untreatable, neurodegenerative disorders. In inducible mouse models of SCA1 and Huntington disease, repression of mutant allele expression improves disease phenotypes. Thus, therapies designed to inhibit expression of the mutant gene would be beneficial. Here we evaluate the ability of RNA interference (RNAi) to inhibit polyglutamine-induced neurodegeneration caused by mutant ataxin-1 in a mouse model of SCA1. Upon intracerebellar injection, recombinant adeno-associated virus (AAV) vectors expressing short hairpin RNAs profoundly improved motor coordination, restored cerebellar morphology and resolved characteristic ataxin-1 inclusions in Purkinje cells of SCA1 mice. Our data demonstrate in vivo the potential use of RNAi as therapy for dominant neurodegenerative disease.
690 citations
Authors
Showing all 49661 results
Name | H-index | Papers | Citations |
---|---|---|---|
Stephen V. Faraone | 188 | 1427 | 140298 |
Jie Zhang | 178 | 4857 | 221720 |
D. M. Strom | 176 | 3167 | 194314 |
Bradley T. Hyman | 169 | 765 | 136098 |
John H. Seinfeld | 165 | 921 | 114911 |
David Jonathan Hofman | 159 | 1407 | 140442 |
Stephen J. O'Brien | 153 | 1062 | 93025 |
John T. Cacioppo | 147 | 477 | 110223 |
Mark Raymond Adams | 147 | 1187 | 135038 |
E. L. Barberio | 143 | 1605 | 115709 |
Andrew Ivanov | 142 | 1812 | 97390 |
Stephen J. Lippard | 141 | 1201 | 89269 |
Russell Richard Betts | 140 | 1323 | 95678 |
Barry Blumenfeld | 140 | 1909 | 105694 |
Marcus Hohlmann | 140 | 1356 | 94739 |