T cell response to two immunodominant proteolipid protein (PLP) peptides in multiple sclerosis patients and healthy controls

Despite the fact that the neuroleptic drugs have been widely used for more than 40 years, one of their most common side-effects, akathisia, has been relatively neglected. There are still no universally agreed diagnostic criteria for akathisia, particularly chronic akathisia, and in this review article, we discuss the controversies surrounding the voluntary nature of its motor features and the importance of the dysphoric component. We also review the published epidemiological studies to show the great variation in frequency of occurrence. Finally, we discuss the possible neurotransmitters involved in the pathophysiology and treatment of this condition.     

Variable distributions of Ca(2+)-permeable and Ca(2+)-impermeable AMPA receptors on embryonic rat dorsal horn neurons

1. By measuring the apparent reversal potential (aErev) of kainate- and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA)-evoked currents associated with changes in extracellular Ca2+ concentration ([Ca2+]e), we have been able to identify embryonic dorsal horn neurons grown in tissue culture that express Ca(2+)-permeable non-N-methyl-D-aspartic acid (NMDA) receptors. 2. The relative expression of Ca(2+)-permeable and Ca(2+)-impermeable non-NMDA receptors varies from cell to cell. This was evident from the range of a ErevS observed for kainate-evoked currents in a 0 mM [Na+]e, 10 mM [Ca2+]e bath. Under these conditions, aErev ranged from -96 to -21 mV, suggesting that the percentage of the non-NMDA receptors on each neuron that are Ca(2+)-permeable is variable. 3. To determine the extent to which the variability in aErev is due to variable receptor expression rather than experimental variability, we compared the effects of changes in [Ca2+]e on kainate-evoked currents and NMDA-evoked currents on the same cells. Assuming that all of the NMDA receptors on each neuron have a similar Ca2+ permeability, this approach provides an index of the sensitivity of our assay system. The reversal potential of NMDA-evoked currents in 10 mM [Ca2+]e ranged from -30 to -7 mV, whereas on the same population of neurons, the aErev of kainate-evoked currents ranged from -92 to -40 mV. 4. The rectification properties of the non-NMDA currents were generally linear or outwardly rectifying in normal bath solution. When the PCa/PCs ratio in 0 mM [Na+]e, 10 mM [Ca2+]e bath solution was assessed as a function of the rectification index in standard bath, a poor correlation was found between Ca2+ permeability and the rectification index. 5. The aErev of kainate-evoked currents was similar to that of cyclothiazide-enhanced AMPA-evoked currents observed on the same cells (-66.5 +/- 18.4 and -64.0 +/- 13.9 mV, mean +/- SD, respectively). This suggests that kainate is primarily activating the AMPA receptor and that the majority of non-NMDA receptors on embryonic dorsal horn neurons in culture are high-affinity AMPA receptors. 6. Immunocytochemical evidence suggests that the AMPA receptor subunits GluR1-4 are expressed to a variable degree from cell to cell in our cultures. We found evidence for low levels of expression of the kainate receptor subunits GluR5-7. The immunocytochemical observations support the physiological data indicating that much of the kainate-evoked current recorded in our experiments can be accounted for by kainate activation of AMPA receptors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Single-laser approach for fluorescence guidance of excimer laser angioplasty at 308 nm: evaluation in vitro and during coronary angioplasty

BACKGROUND AND OBJECTIVE: Spectroscopic guidance of laser angioplasty has been attempted using a diagnostic He-Cd laser in addition to the therapeutic laser system. This study evaluated a single-laser approach for simultaneous ablation and fluorescence excitation. STUDY DESIGN/MATERIALS AND METHODS: A spectroscopy system was coupled to a clinical XeCl excimer laser. Ablation of 162 human aortic samples in saline and blood with 45 mJ/mm2 per pulse yielded 676 fluorescence spectra validated histologically. The same equipment was used in 16 patients for angioplasty of 18 coronary stenoses applying 500 to 1,725 pulses with 45 to 60 mJ/mm2 under saline flushing. A total of 783 spectra were recorded and validated by intracoronary ultrasound (categories: atheroma, fibrous plaque, calcified lesion). RESULTS: In vitro, 5 types of spectra could be differentiated: (1) atheroma, (2) fibrous plaque, (3) calcified lesion in saline, (4) media, and (5) calcified lesion in blood. Discriminant analysis prospectively classified 576 validation spectra with the following sensitivity and specificity for each type: (1) 83.5 and 97.1%, (2) 85.7 and 96.8% (3) 100 and 98.5%, (4) 98.1 and 99.3%, (5) 98.9 and 100%, respectively. In vivo type 1, 2, 3, and 5 spectra were also observed, but not the media spectrum. The predominant sonographic category also prevailed in spectroscopy. Calcified lesions yielded type 3 and 5 as well as mixed spectra. CONCLUSIONS: Using an excimer laser for angioplasty allows combining ablation and fluorescence excitation without a diagnostic laser. Principal types of atherosclerotic lesions and the media can be differentiated spectroscopically with this approach.     

Evaluation of the uncertainty of molecular mass measurement by electrospray ionization mass spectrometry

Electrospray ionization (ES) is a novel method used in mass spectrometry (MS) for producing gas-phase ions from substances in solutions. Common practices for molecular mass estimation from ES spectra summarize the spectrum as a single peak giving no estimate of uncertainty or treat each peak as an independent molecular mass measurement. ES-MS data analysis showed that each peak in an ES spectrum does not always provide an independent measure of molecular mass. Underestimation of measurement uncertainty is a possible result. An elementary time series method, the Yule-Walker equations, was applied to molecular mass estimation from ES data.     

Evaluation of a new enzyme immunoassay for Clostridium difficile toxin A

AIM: To evaluate a new enzyme immunoassay (EIA) method for detection of Clostridium difficile toxin by comparing it to cytotoxicity assay. To investigate the nature of false negative and false positive EIA results by evaluating clinical and therapeutic parameters. METHODS: 737 consecutive diarrhoeal specimens collected from patients clinically suspected of having C difficile colitis were tested for the presence of C difficile toxin by EIA for toxin A and by cytotoxicity assay. Clinical data were evaluated in all cases positive by either method. RESULTS: With the cytotoxicity assay as a gold standard, the specificity of EIA for toxin detection was 99.3% and the sensitivity was 62.2%. No false negative EIA specimens were obtained from patients already being treated for C difficile colitis. Among patients with cytotoxicity positive specimens, those with EIA positive samples had no clinical features distinguishing them from patients with EIA negative samples. CONCLUSIONS: Although specific, the new EIA method directed against toxin A lacks sensitivity compared to cytotoxicity. False negative EIA tests are not associated with concurrent treatment for C difficile colitis nor with any specific clinical features examined in our study.     

Cell signaling by the type IV pili of pathogenic Neisseria

Neisseria gonorrhoeae and Neisseria meningitidis are Gram-negative bacterial pathogens that infect human mucosal epithelia. Type IV pilus-mediated adherence of these bacteria is a crucial early event for establishment of infection. In this work, we show that the type IV pili transduce a signal into the eucaryotic host cell. Purified adherent pili, but not pili from a low binding mutant, trigger an increase in the cytosolic free calcium ([Ca2+]i) in target epithelial cells, a signal known to control many cellular responses. The [Ca2+]i increase was blocked by antibodies against CD46, a putative pilus receptor, suggesting a role for this protein in signal transduction. Pilus-mediated attachment was inhibited by depletion of host cell intracellular Ca2+ stores but not by removal of extracellular Ca2+. Further, kinase inhibition studies showed that pilus-mediated adherence is dependent on casein kinase II. In summary, these data reveal a novel function of the type IV pili, namely induction of signal transduction pathways in host cells.     

Psychophysical evidence for a functional hierarchy of motion processing mechanisms

Current models of motion perception typically describe mechanisms that operate locally to extract direction and speed information. To deal with the movement of self or objects with respect to the environment, higher-level receptive fields are presumably assembled from the outputs of such local analyzers. We find that the apparent speed of gratings viewed through four spatial apertures depends on the interaction of motion directions among the apertures, even when the motion within each aperture is identical except for direction. Specifically, local motion consistent with a global pattern of radial motion appears 32% faster than that consistent with translational or rotational motion. The enhancement of speed is not reflected in detection thresholds and persists in spite of instructions to fixate a single local aperture and ignore the global configuration. We also find that a two-dimensional pattern of motion is necessary to elicit the effect and that motion contrast alone does not produce the enhancement. These results implicate at least two serial stages of motion-information processing: a mechanism to code the local direction and speed of motion, followed by a global mechanism that integrates such signals to represent meaningful patterns of movement, depending on the configuration of the local motions.