MRI demonstration of impairment of the blood-CSF barrier by glucose administration to the thiamin-deficient rat brain

Contrast-enhanced T1-weighted spin-echo magnetic resonance imaging (MRI) has demonstrated that Gd-diethylenetriaminepentaacetate (Gd-DTPA), which normally does not cross the blood-brain or blood-CSF barriers, does so approximately 40 min after administration of glucose to a vitamin B1 deficient rat. The period of the onset of this blood-CSF or blood-brain barrier dysfunction coincides with our previous observations of accumulation of glutamate or glutamate derivatives following an equivalent glucose load under identical conditions of thiamin deficiency, consistent with a relationship between these two observations. The dysfunction was reversed when a thiamin deficient animal was made thiamin replete.     

Measurement of helium metastable atom densities in a plasma-based ambient ionization source

We describe direct imaging of the densities of helium metastable atoms in the afterglow of a helium dielectric-barrier discharge (He-DBD) using collisionally assisted laser-induced fluorescence (LIF). For the conditions tested, comparison of fluorescence images of a He-DBD with analogous maps of emission from highly excited helium atoms revealed that helium metastable atom densities did not correlate well with emission from the plasma. Fluorescence images also showed that helium metastable atom densities increased substantially when a glass slide was placed 10.0 mm from the discharge capillary in a geometry typical for desorption-ionization experiments. We also studied the effect hydrogen has on the helium metastable atom densities. The hydrogen severely quenched the metastable state leaving it virtually undetectable. Emission was quenched as well, but to a lesser extent. The addition of 1% H(2) to the helium in the source provided nearly a factor of 2 improvement in the sensitivity of the signal for coumarin 47 when the plasma was used to ionize the dye under ambient conditions, despite the quenching of the helium metastable atom population.     

Coherent Optical Recognition and Counting of Reticulated Red Blood Cells

A coherent optical data-processing system for identifying and counting blood cells has been developed. Optical Weiner-Kolmogorov (minimum mean-square error) linear filtering is employed to estimate the density per unit area of a given cell type present in a sample blood smear. The Weiner filter is designed to recognize the characteristics of an ensemble of cells of a type rather than specific individual cells. In this way the system is made insensitive to minor variations in shape, size, or orientation of the cells. A Poisson shot-noise model for blood cells as a spatial random process is employed to calculate the far-field scattering from the cells. Results of experiments in which the percentage of reticulated (immature) red cells present in a smear has been determined are presented. The identification and counting accuracies compare favorably with those obtained by laboratory technicians with a microscope. The potential time saving of instantaneous estimation for the entire smear is significant.     

Diskitis caused by Actinobacillus actinomycetemcomitans

A 32-year-old man with acquired immunodeficiency syndrome (AIDS) admitted to the hospital for treatment of visceral leishmaniasis was inadvertently given 10 times the prescribed first dose of sodium stibogluconate ([Sb] 6.5 g instead of 0.65 g). He experienced no immediate major toxicity during the first 48 hours, but a significant rise of pancreatic enzyme activities was observed (amylase at 10 times the upper limit of normal, lipase at 50 times the upper limit of normal) without clinical signs or indications on computed tomography (CT) of pancreatitis. The third day after the overdose, he developed appendicitis, which appeared coincidental; he recovered uneventfully from surgery. Most of the overdose of Sb was eliminated within the first few hours. Pharmacokinetics remained linear; the rapid, long elimination half-lives (2.7 hours and 54 hours, respectively) were similar to those in previously published results. The administration of a chelating agent, dimercaptosuccinic acid (DMSA), 72 hours after the Sb overdose did not modify the pharmacokinetics of the medication.     

Training genetic programming on half a million patterns: an example from anomaly detection

The hierarchical RSS-DSS algorithm is introduced for dynamically filtering large datasets based on the concepts of training pattern age and difficulty, while utilizing a data structure to facilitate the efficient use of memory hierarchies. Such a scheme provides the basis for training genetic programming (GP) on a data set of half a million patterns in 15 min. The method is generic, thus, not specific to a particular GP structure, computing platform, or application context. The method is demonstrated on the real-world KDD-99 intrusion detection data set, resulting in solutions competitive with those identified in the original KDD-99 competition, while only using a fraction of the original features. Parameters of the RSS-DSS algorithm are demonstrated to be effective over a wide range of values. An analysis of different cost functions indicates that hierarchical fitness functions provide the most effective solutions.     

Restriction endonuclease profiles of orf virus isolates from the British Isles

A comparison of DNA profiles of representative isolates of orf virus, obtained using four different restriction endonucleases (RE), showed that the enzyme EcoRI could be used to discriminate between wild-type virus isolates and vaccine strains. The enzyme was used to compare the RE profiles of orf virus isolates from 43 outbreaks of orf that occurred in vaccinated flocks between 1988 and 1993; 21 outbreaks yielded wild-type virus, 10 yielded vaccine viruses, three produced both vaccine and wild-type viruses and no clear result was obtained from nine of the outbreaks. From the 21 outbreaks yielding wild-type viruses, 28 orf virus isolates had clear RE profiles and 15 distinct RE profiles were recorded. Usually only one virus type was associated with each outbreak but from two farms, two different wild-type viruses were recovered. No predominant genotype was identified, with four RE profile types being recovered for more than one outbreak. From the more severe form of orf involving the buccal cavities of lambs only wild-type viruses were recovered, with at least four different genotypes being represented.     

Three-dimensional solution structure of alpha-conotoxin MII by NMR spectroscopy: effects of solution environment on helicity

alpha-Conotoxin MII, a 16-residue polypeptide from the venom of the piscivorous cone snail Conus magus, is a potent and highly specific blocker of mammalian neuronal nicotinic acetylcholine receptors composed of alpha3 beta2 subunits. The role of this receptor type in the modulation of neurotransmitter release and its relevance to the problems of addiction and psychosis emphasize the importance of a structural understanding of the mode of interaction of MII with the alpha3 beta2 interface. Here we describe the three-dimensional solution structure of MII determined using 2D 1H NMR spectroscopy. Structural restraints consisting of 376 interproton distances inferred from NOEs and 12 dihedral restraints derived from spin-spin coupling constants were used as input for simulated annealing calculations and energy minimization in the program X-PLOR. The final set of 20 structures is exceptionally well-defined with mean pairwise rms differences over the whole molecule of 0.07 A for the backbone atoms and 0.34 A for all heavy atoms. MII adopts a compact structure incorporating a central segment of alpha-helix and beta-turns at the N- and C-termini. The molecule is stabilized by two disulfide bonds, which provide cross-links between the N-terminus and both the middle and C-terminus of the structure. The susceptibility of the structure to conformational change was examined using several different solvent conditions. While the global fold of MII remains the same, the structure is stabilized in a more hydrophobic environment provided by the addition of acetonitrile or trifluoroethanol to the aqueous solution. The distribution of amino acid side chains in MII creates distinct hydrophobic and polar patches on its surface that may be important for the specific interaction with the alpha3beta2 neuronal nAChR. A comparison of the structure of MII with other neuronal-specific alpha-conotoxins provides insights into their mode of interaction with these receptors.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

BACKGROUND: Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far. METHODS: Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined. RESULTS: At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1 +/- 1.2% (mean +/- SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2 +/- 1.2%), sevoflurane (to 4.4 +/- 0.9%) or halothane (to 3.2 +/- 1.5%) (each P < 0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics. CONCLUSION: Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.