Comparison of left ventricular electromechanical mapping and left ventricular angiography: defining practical standards for analysis of NOGA maps

We performed this prospective cohort study to correlate the findings of left ventricular angiography (LVA) and NOGA left ventricular electromechanical mapping (LVEM) in the evaluation of cardiac wall motion and also to establish standards for wall motion assessment by LVEM. Fifty-five patients (35 men; mean age, 60.4 +/- 11.8 years) eligible for elective left cardiac catheterization underwent LVA and LVEM. Wall motion scores, LV ejection fractions (LVEF), and LV volumes derived from LVA versus LVEM data were compared and analyzed statistically. Receiver operating characteristic (ROC) curves were used to assess the accuracy of LVEM in distinguishing between normal, hypokinetic, and akinetic/dyskinetic wall motion. Mean LVEM procedure time was 37 +/- 11 minutes. The LVEM and LVA findings differed for mean LVEF (55% +/- 13% vs 36% +/- 9%), mean end-systolic volume (56 +/- 13 mL vs 36 +/- 10 mL), and mean end-diastolic volume (174 +/- 104 mL vs 123 +/- 65 mL). Mean wall motion scores (+/- SD) for normokinetic, hypokinetic, and akinetic/dyskinetic segments were 13.9% +/- 5.6%, 8.3% +/- 5.2%, and 3.2% +/- 3.1%, respectively. Cutpoints for differentiating between wall motion types were 12% and 6%. The ROC curves showed LVEM to have a 93% accuracy in differentiating between normokinetic and akinetic/dyskinetic segments and a 73% accuracy between normokinetic and hypokinetic segments. These data suggest that LVEM can differentiate between normal and abnormal cardiac wall motion, although it is more accurate at differentiating between normokinetic and akinetic/dyskinetic motion than between normokinetic and hypokinetic motion.     

Analysis of the binding surfaces of proteins.

We have developed an experimental approach to map the complete binding surface of any crystalline macromolecule that is fast and flexible. Crystals of the target protein are transferred into organic solvents and the crystal structures are determined at high (about 2A) resolution. The sites where the solvent molecules bind to the protein are thus identified directly. Different solvents serve as probes for different organic functional groups; thus, benzene is a probe for where aromatic groups like to bind, dimethyl formamide is a probe for peptide binding sites, and so forth. A series of about six such experiments suffices to locate the major binding regions on the protein surface unambiguously. These different sites can then be targeted with "Hydra-headed" inhibitors that interact simultaneously with more that one site, thereby providing specificity for the desired target. We have used this method to map the complete binding surface of elastase, and find that three regions, including the active site cleft, are generally "sticky" and can make interactions with almost any functional group. Analyses of these binding sites on elastase and other proteins suggests that what makes a binding site is amphipathicity and the ease with which water can be displaced.     

High Frequency of Nonrecurrent MECP2 Duplications Among Brazilian Males with Mental Retardation

Structural variations that affect the copy number of the MECP2 gene were shown to cause mental retardation in males by driving the overexpression of this gene. To access the impact of these rearrangements in males with unexplained mental retardation, we have performed a quantitative real-time polymerase chain reaction assay using SYBR Green I chemistry to quantify MECP2 gene copy number in 145 Brazilian males with mental retardation of unknown cause. Three patients carrying MECP2 duplications (~2%) were identified. The analysis of additional markers flanking the MECP2 region showed that the duplications observed are nonrecurrent. Expression studies in two of these patients revealed the overexpression of the MECP2 gene compared to the expression level observed in controls. These findings corroborate other recent reports in the literature and highlight that the overexpression of MECP2 caused by duplications involving this gene is a relatively frequent genetic cause of mental retardation in males, highlighting the importance of MECP2 gene dosage for diagnostic purposes in such cases.     

β-Galactofuranose-containing structures present in the cell wall of the saprophytic fungus Cladosporium (Hormoconis) resinae

A peptidogalactomannan was isolated from mycelia of Cladosporium (Hormoconis) resinae and characterized using methylation–fragmentation analysis, partial acid hydrolysis and ¹H and ¹³C-NMR spectroscopy. The galactomannan component was a branched structure and consisted of a main chain containing (1→6)-linked α-d-Manp residues substituted at O-2 by side chains containing (1→2)-linked α-d-Manp residues. β-d-Galf residues were present as side chains of 3–4 units that are (1→5)-interlinked. This structure is very similar to a pGM isolated from Aspergillus fumigatus and differs from that of Cladosporium werneckii (currently named Hortaea werneckii), with this pGM and other fungal galactomannans having single terminal (1→6)-linked β-Galf residues. The importance of the carbohydrate moiety of Cladosporium resinae pGM in immunoassays was also demonstrated. On FACS examination, a decrease (60%) in rabbit serum anti- C. resinae binding to C. resinae conidia occurred when this serum had been previously incubated with pGMs from C. resinae and A. fumigatus or with mannoprotein from Candida parapsilosis, suggesting the presence of cross-reactive determinants in these fungi.     

Pterodon pubescens seed extract induces the cell cycle arrest of leukemic cells by deregulating cyclin D1 and E2 mRNA levels

Plant-derived compounds are important sources of effective anti-cancer agents. Pterodon pubescens is a native Brazilian plant popularly known for its anti-inflammatory and anti-arthritic effects. The ethanolic extract of its seeds (EEPp) is a viscous, brown and fragrant oil containing geranylgeraniol, farnesol, naphthalene, dimethyldodecatrienol and vouacapan diterpene derivatives, in addition to other compounds. This study investigated the in vitro anti-leukemic properties of EEPp using the resistant human leukemia cell line K562. The EEPp anti-proliferative effect was demonstrated by the inhibition of DNA synthesis and cell growth, and the induction of cell cycle arrest in the G(1) phase. Furthermore, cyclin E2 mRNA levels were down-regulated, while those of cyclin D1 were up-regulated. An EEPp anti-leukemic effect may have also triggered apoptosis, as it increased the number of shrunken cells and phosphatidylserine cell membrane exposure. These observations suggest that EEPp deregulates cyclin D1 and E2 expression, inducing cell cycle arrest and apoptosis of leukemic cells.