Electrocorticographic correlates of cognitive control in a stroop task—intracranial recording in epileptic patients

The human brain executes cognitive control, such as selection of relevant information in the presence of competing irrelevant information, and cognitive control is essential for us to yield a series of optimal behaviors in our daily life. This study assessed electrocorticographic γ‐oscillations elicited by cognitive control in the context of the Stroop color‐naming paradigm, with a temporal resolution of 10 msec and spatial resolution of 1 cm. Subjects were instructed to overtly read a color word printed in an incongruent color in the reading task, and to overtly name the ink color of a color word printed in an incongruent color in the Stroop color‐naming task. The latter task specifically elicited larger γ‐augmentations in the dorsolateral‐premotor, dorsolateral‐prefrontal and supplementary motor areas with considerable inter‐subject spatial variability. Such Stroop color‐naming‐specific γ‐augmentations occurred 500 to 200 msec prior to overt responses. Electrical stimulation of the sites showing Stroop color‐naming‐specific γ‐augmentations resulted in temporary naming impairment more frequently than that of the remaining sites. This study has provided direct evidence that a critical process of cognitive control in the context of Stroop color‐naming paradigm consists of recruitment of neurons essential for naming located in variable portions of the dorsolateral premotor and prefrontal areas. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96736/1/21129_ftp.pd

Effect of introduction of chondroitin sulfate into polymer-peptide conjugate responding to intracellular signals

We recently developed a novel tumor-targeted gene delivery system responding to hyperactivated intracellular signals. Polymeric carrier for gene delivery consists of hydrophilic neutral polymer as main chains and cationic peptide substrate for target enzyme as side chains, and was named polymer-peptide conjugate (PPC). Introduction of chondroitin sulfate (CS), which induces receptor-medicated endocytosis, into polymers mainly with a high cationic charge density such as polyethylenimine can increase tumor-targeted gene delivery. In the present study, we examined whether introduction of CS into PPC containing five cationic amino acids can increase gene expression in tumor cells. Size and zeta potential of plasmid DNA (pDNA)/PPC/CS complex were <200 nm and between -10 and -15 mV, respectively. In tumor cell experiments, pDNA/PPC/CS complex showed lower stability and gene regulation, compared with that of pDNA/PPC. Moreover, no difference in gene expression was identified between positive and negative polymer. These results were caused by fast disintegration of pDNA/PPC/CS complexes in the presence of serum. Thus, we suggest that introduction of negatively charged CS into polymers with a low charge density may lead to low stability and gene regulation of complexes

Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts

<p>Abstract</p> <p>Background</p> <p>Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active.</p> <p>Methods</p> <p>The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production.</p> <p>Results</p> <p>ECI carrying a chitobiose unit, ECI-(GlcNAc) ₂, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)₃(GlcNAc)₂], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)₂.</p> <p>Conclusions</p> <p>Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.</p

The glycated albumin to HbA1c ratio is elevated in patients with fulminant type 1 diabetes mellitus with onset during pregnancy

Fulminant type 1 diabetes mellitus (FT1DM) develops as a result of very rapid and almost complete destruction of pancreatic β cell. The most common form of type 1 diabetes mellitus with onset during pregnancy has been shown to be FT1DM at least in Japan. We previously reported that the ratio of glycated albumin (GA) to HbA1c (GA/HbA1c ratio) is elevated in FT1DM patients at the diagnosis. In the present study, we investigated whether the GA/HbA1c ratio is also elevated in FT1DM with onset during pregnancy (P-FT1DM). The study subjects consisted of 7 patients with P-FT1DM. Ten patients with untreated type 2 diabetes mellitus (T2DM) discovered during pregnancy (P-T2DM) and 9 non-pregnant women with untreated T2DM (NP-T2DM) were used as controls. All study patients satisfied HbA1c<8.7%, the diagnostic criteria for FT1DM. The GA/HbA1c ratio in the P-FT1DM patients at the diagnosis was significantly higher than that in the P-T2DM patients and the NP-T2DM patients. The GA/HbA1c ratio was ≥3.0 in all P-FT1DM patients, whereas it was <3.0 in 8 of 10 P-T2DM patients and all NP-T2DM patients. The GA/HbA1c ratio was also elevated in P-FT1DM patients at the diagnosis compared with T2DM with or without pregnancy

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation