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Amyotrophic lateral sclerosis (ALS) is a generally fatal neurodegenerative disease of adults that produces weakness and atrophy due to dysfunction and death of upper and lower motor neurons. We used RNA-sequencing (RNA-seq) to analyze expression of all mitochondrial DNA (mtDNA)-encoded respiratory genes in ALS and CTL human cervical spinal cords (hCSC) and isolated motor neurons. We analyzed with RNA-seq mtDNA gene expression in human neural stem cells (hNSC) exposed to recombinant human mitochondrial transcription factor A (rhTFAM), visualized in 3-dimensions clustered gene networks activated by rhTFAM, quantitated their interactions with other genes and determined their gene ontology (GO) families. RNA-seq and quantitative PCR (qPCR) analyses showed reduced mitochondrial gene expression in ALS hCSC and ALS motor neurons isolated by laser capture microdissection (LCM), and revealed that hNSC and CTL human cervical spinal cords were similar. Rats treated with i.v. rhTFAM showed a dose-response increase in brain respiration and an increase in spinal cord mitochondrial gene expression. Treatment of hNSC with rhTFAM increased expression of mtDNA-encoded respiratory genes and produced one major and several minor clusters of gene interactions. Gene ontology (GO) analysis of rhTFAM-stimulated gene clusters revealed enrichment in GO families involved in RNA and mRNA metabolism, suggesting mitochondrial-nuclear signaling. In postmortem ALS hCSC and LCM-isolated motor neurons we found reduced expression of mtDNA respiratory genes. In hNSC's rhTFAM increased mtDNA gene expression and stimulated mRNA metabolism by unclear mechanisms. rhTFAM may be useful in improving bioenergetic function in ALS.

ObjectivesThe goal of this study was to assess the relationship among extracellular volume (ECV), native T1, and systolic strain in hypertensive patients with left ventricular hypertrophy (HTN LVH), hypertensive patients without LVH (HTN non-LVH), and normotensive controls.BackgroundDiffuse myocardial fibrosis in HTN LVH patients, as reflected by increased ECV and native T1, may be an underlying mechanism contributing to increased cardiovascular risk compared with HTN non-LVH subjects and controls. Furthermore, increased diffuse fibrosis in HTN LVH subjects may be associated with reduced peak systolic and early diastolic strain rate compared with the other 2 groups.MethodsT1 mapping was performed in 20 HTN LVH (mean age, 55 ± 11 years), 23 HTN non-LVH (mean age, 61 ± 12 years), and 22 control subjects (mean age, 54 ± 7 years) on a Siemens 1.5-T Avanto (Siemens Healthcare, Erlangen, Germany) using a previously validated modified look-locker inversion-recovery pulse sequence. T1 was measured pre-contrast and 10, 15, and 20 min after injection of 0.15 mmol/kg gadopentetate dimeglumine, and the mean ECV and native T1 were determined for each subject. Measurement of circumferential strain parameters were performed using cine displacement encoding with stimulated echoes.ResultsHTN LVH subjects had higher native T1 compared with controls (p < 0.05). HTN LVH subjects had higher ECV compared with HTN non-LVH subjects and controls (p < 0.05). Peak systolic circumferential strain and early diastolic strain rates were reduced in HTN LVH subjects compared with HTN non-LVH subjects and controls (p

Objectives The purpose of this paper was to compare quantitative cardiac magnetic resonance (CMR) first-pass contrast-enhanced perfusion imaging to qualitative interpretation for determining the presence and severity of coronary artery disease (CAD). Background Adenosine CMR can detect CAD by measuring perfusion reserve (PR) or by qualitative interpretation (QI). Methods Forty-one patients with an abnormal nuclear stress scheduled for X-ray angiography underwent dual-bolus adenosine CMR. Segmental myocardial perfusion analyzed using both QI and PR by Fermi function deconvolution was compared to quantitative coronary angiography. Results In the 30 patients with complete quantitative data, PR (mean ± SD) decreased stepwise as coronary artery stenosis (CAS) severity increased: 2.42 ± 0.94 for 70% (p 50% (83% vs. 80%), and CAS >70% (77% vs. 67%). Agreement between observers was higher for quantitative analysis than for qualitative analysis. Using PR, patients with triple-vessel CAD had a higher burden of detectable ischemia than patients with single-vessel CAD (60% vs. 25%; p = 0.02), whereas no difference was detected by QI (31% vs. 21%; p = 0.26). In segments with myocardial scar (n = 64), PR was 3.10 ± 1.34 for patients with CAS 50% (p Conclusions Quantitative PR by CMR differentiates moderate from severe stenoses in patients with known or suspected CAD. The PR analysis differentiates triple- from single-vessel CAD, whereas QI does not, and determines the severity of CAS subtending myocardial scar. This has important implications for assessment of prognosis and therapeutic decision making.