Solution conformation of the Pseudomonas syringae MSU 16H phytotoxic lipodepsipeptide Pseudomycin A determined by computer simulations using distance geometry and molecular dynamics from NMR data

Pseudomycin A is a cyclic lipodepsinonapeptide phytotoxin produced by a strain of the plant pathogenic bacterium Pseudomonas syringae. Like other members of this family of bacterial metabolites, it is characterised by a fatty acylated cyclic peptide with mixed chirality and lactonic closure. Several biological activities of Pseudomycin A are lower than those found for some of its congeners, a difference which might depend on the diverse number and distribution of charged residues in the peptide moiety. Hence, it was of interest to investigate its conformation in solution. After the complete interpretation of the two-dimensional NMR spectra, NOE data were obtained and the structure was determined by computer simulations, applying distance geometry and molecular dynamics procedures. The conformation of the large ring of Pseudomycin A in solution includes three rigid structural regions interrupted by three short flexible regions that act as hinges. The overall three-dimensional structure of the cyclic moiety is similar to that of previously studied bioactive lipodepsinonapeptides produced by other pseudomonads.     

Use of exercise technetium-99m sestamibi SPECT imaging to detect residual ischemia and for risk stratification after acute myocardial infarction

The clinical presentation, electrocardiographic findings, and technetium-99m sestamibi single-photon emission computed tomography (SPECT) imaging results of 134 consecutive patients who underwent nuclear exercise testing within 14 days of an acute myocardial infarction (AMI) were correlated with cardiac events over a 15 +/- 10-month follow-up. Whereas only 23 patients (17%) had chest pain and 31 (23%) had ischemic ST-segment depression during exercise, 94 (70%) had ischemia on SPECT (p < 0.001). On follow-up, 13 patients experienced a cardiac event: 7 were rehospitalized for unstable angina, 3 had recurrent AMI, and 3 died of cardiac causes. Ischemia on the sestamibi images identified 11 of these patients (85%), whereas chest pain identified only 3 (23%, p = 0.006), and electrocardiographic ischemia identified only 4 (31%, p = 0.017). The presence of either ischemia as seen on SPECT or defects in multiple vascular territories identified 12 patients (92%) with an event, including all who had cardiac death. By Cox regression analysis of clinical, stress, and image parameters, the number of ischemic defects on SPECT was the only significant correlate of a future event (chi-square = 4.62, p = 0.03), and patients with > or = 3 reversible sestamibi defects had an event rate of 38%. The extent of ischemia as seen on nuclear imaging remained a strong correlate (p = 0.008) of an event in the 54 patients (40%) who had received thrombolytic therapy. Thus, exercise technetium-99m sestamibi SPECT after AMI frequently reveals residual ischemia, and is better than clinical data, symptoms, and stress electrocardiographic data in identifying patients who will have a subsequent cardiac event.     

Ligands with affinity to specific sequences of DNA base pairs. X. Synthesis and binding of netropsin analogs, containing a chelating copper ion peptide, with DNA

An analogue of netropsin has been synthesized consisting of two N-propylpyrrolcarboxamide units linked covalently to a copper-chelating tripeptide Gly-Gly-L-His by means of two and three glycine residues. Binding to DNA and synthetic polynucleotides of netropsin analogue containing three glycine residues between Gly-Gly-L-His tripeptide and the N-end of netropsin analogue (His-Nt) has been studied. It is shown that this netropsin analogue chelates a copper ion with 1:1 stoichiometry, similar to a free Gly-Gly-L-His peptide. It is found that this netropsin analogue occupies 3 to 4 base pairs upon binding to poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers, irrespective of whether it binds in Cu(2+)-ligated or unligated forms. Binding constants and binding site sizes have been calculated for netropsin analogue complexes with DNA, poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers at the [Cu2+]/[His-Nt] ratio equal to 0 and 1.0. In the three-component system including His-Nt and Cu(2+)-His-Nt, cooperative effects are recognized which can be explained by heterodimer generation on interaction of His-Nt and Cu(2+)-His-Nt at adjacent binding sites.     

Disability among the population of the Russian Federation

Previously we demonstrated that in the course of intracellular reproduction of WSN influenza virus strain, part of monomeric nucleoprotein (NP) undergo polymerization into dimers and trimers, which dissociate into monomers after boiling. Further studies showed that different strains of influenza virus are characterized by different degree of NP-oligomerization. Specifically, Duck/ Ukraine/63 (H3N8) and Seal Massacuhsets 1/80 (H7N7) NP monomers are completely transformed into oligomers. As a result of 40-min chase and of prolonged label exposure only NP-oligomers but not monomers can be detected in unboiled samples of infected cells or in virions. NP monomers of A/Duck/Ukraine strain are detectable in unboiled samples only after a short period of labeling. Influenza virus NP oligomers are more hydrophobic than NP monomers. Oligomers are hypothesized to be the native functionally important form of influenza virus NP.     

Renal osteodystrophy in diabetic patients

To assess the effects of diabetes mellitus on renal osteodystrophy, we examined the database of 256 patients (45% on hemodialysis and 55% on peritoneal dialysis) who were prospectively studied in three Toronto dialysis centers between October of 1987 and 1989. All patients had serial documentation of their clinical, laboratory and risk parameters of bone disease, and completed a series of investigations that included the deferoxamine test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Twenty-five percent of these patients were diabetic. When compared to non-diabetic patients, they were on dialysis for a shorter duration (2.4 +/- 0.3 vs. 4.7 +/- 0.3 years; P < 0.0002), used calcium carbonate as the only phosphate binder more frequently (40 vs. 25%; P < 0.007), and had lower parathyroid hormone levels (12 +/- 1.4 vs. 24 +/- 2.3 pmol/liter; P < 0.002). High-turnover bone disorders (that is, osteitis fibrosa and mixed disorder) were distinctly uncommon (8 vs. 33%; P < 0.01 by Fisher's exact test), while the mild (19 vs. 9%; P = NS) and the aplastic disorders (with mean stainable bone surface aluminum of 6.5 +/- 0.7%) (46 vs. 31%; P = NS) tended to be more common in diabetic patients. The prevalence of aluminum bone disease was the same in both groups (27%). Diabetic patients ingested a smaller cumulative dose of aluminum gels (3.7 +/- 0.6 vs. 9.3 +/- 1.1 kg; P < 0.005), yet had a higher rate of aluminium accumulation on bone surfaces than non-diabetic patients (1.5 +/- 0.19 vs. 0.96 +/- 0.10% per month on dialysis; P < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)     

A decade of clinical trial developments in postmyocardial infarction, congestive heart failure, and sustained ventricular tachyarrhythmia patients: from CAST to AVID and beyond. Cardiac Arrhythmic Suppression Trial. Antiarrhythmic Versus Implantable Defibrillators

Multiple trials using antiarrhythmic drugs, pharmacologic therapy, and implantable cardioverter defibrillators have been performed in an attempt to improve survival in patients: (1) postmyocardial infarction; (2) with congestive heart failure, with and without nonsustained ventricular tachycardia; and (3) with sustained ventricular tachycardia and those who have survived an out-of-hospital cardiac arrest. This article reviews some of the key findings and limitations of completed and ongoing trials. We also make recommendations for the current treatment of such patients based on the results of these trials.     

Computer modeling of the neural network recognizing the contrasts on the image

Computer modeling of the neuron network offered in [1] is discussed. Organization and feature of modeling are described, as well as the changes, which are introduced in the network during researches. Results of modeling are present.