Comparison of anaesthetic and non-anaesthetic effects on depolarization-evoked glutamate and GABA release from mouse cerebrocortical slices

The aim of the study was to investigate whether patients with Aspergillus-induced lung disease can be monitored by immunoblot analysis to detect antibodies to Aspergillus fumigatus (Af). Immunoblotting was performed by incubating 57 longitudinally collected sera from 13 patients on nitrocellulose sheets, blotted with Af antigen, separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Bound antibodies were demonstrated by peroxidase-labelled antihuman immunoglobulins (Ig)G and IgA antiserum and diaminobenzidine plus H2O2 as substrate. The immunoblot patterns were related to the patients' clinical status and time. Each patient had a characteristic immunoblot pattern that varied with time. There was a relationship between disease activity or clinical response and changes in immunoblot antibody patterns: a rise in anti-Af IgG and IgA antibodies was seen in sera collected during active disease, compared with before active disease, and a significant decline in anti-Af IgG and IgA was demonstrated in sera collected during recovery, compared with during active disease. Only in the acute stage of allergic bronchopulmonary aspergillosis were IgA antibodies against Af antigens of <20,000 Da demonstrated. Immunoblot analysis can be used to monitor the disease activity and the responses to treatment of patients with Aspergillus-induced lung diseases. Changes in specific immunoglobulin A may be more informative than specific immunoglobulin G.     

Comparative evaluation of the use of artificial neural networks for modelling the epidemiology of schistosomiasis mansoni

There has been a marked increase in the application of approaches based on artificial intelligence (AI) in the field of computer science and medical diagnosis, but AI is still relatively unused in epidemiological settings. In this study we report results of the application of neural networks (NN; a special category of AI) to schistosomiasis. It was possible to design an NN structure which can process and fit epidemiological data collected from 251 schoolchildren in Egypt using the first year's data to predict second and third years' infection rates. Data collected over 3 years included age, gender, exposure to canal water and agricultural activities, medical history and examination, and stool and urine parasitology. Schistosoma mansoni infection rates were 50%, 78% and 66% at the baseline and the 2 follow-up periods, respectively. NN modelling was based on the standard back-propagation algorithm, in which we built a suitable configuration of the network, using the first year's data, that optimized performance. It was implemented on an IBM compatible computer using commercially available software. The performance of the NN model in the first year compared favourably with logistic regression (NN sensitivity = 83% (95% confidence interval [CI] 78-88%) and positive predictive value (PPV) = 63% (95% CI 57-69%); logistic regression sensitivity = 66% (95% CI 60%-72%) and PPV = 59% (95% CI 53%-65%). The NN model generalized the criteria for predicting infection over time better than logistic regression and showed more stability over time, as it retained its sensitivity and specificity and had better false positive and negative profiles than logistic regression. The potential of NN-based models to analyse and predict wide-scale control programme data, which are inevitably based on unstable egg excretion rates and insensitive laboratory techniques, is promising but still untapped.     

Three-dimensional, finite deformation, viscoplastic constitutive models for polymeric materials

A general methodology for developing three-dimensional. finite deformation, viscoplastic constitutive models for polymeric materials is presented. The development begins with the presentation of a one-dimensional spring and dashpot construction which exhibits behavior typical of polymeric materials, namely strain-rate dependence, stress relaxation, and creep. The one-dimensional construction serves as a starting point for the development of a three-dimensional, finite deformation, viscoplastic constitutive model which also exhibits typical polymeric behavior. Furthermore, the three-dimensional constitutive model may be easily generalized to incorporate an arbitrary number of inelastic processes, representing (inelastic) microstructural deformation mechanisms operating on different time scales. Strain-rate dependence, stress relaxation, and creep phenomena are discussed in detail for a simple version of the constitutive model. Test data for a particular polymer is used to validate the simple model. It is concluded that the methodology provides a flexible approach to modeling polymeric materials over a wide range of loading conditions.     

Immunity to T cell receptor peptides in multiple sclerosis. III. Preferential immunogenicity of complementarity-determining region 2 peptides from disease-associated T cell receptor BV genes

Vaccination with synthetic TCR peptides from the BV5S2 complementarity-determining region 2 (CDR2) can boost significantly the frequency of circulating CD4+ peptide-specific Th2 cells in multiple sclerosis (MS) patients, with an associated decrease in the frequency of myelin basic protein (MBP)-reactive Th1 cells and possible clinical benefit. To evaluate the immunogenicity of CDR2 vs other regions of the TCR, we vaccinated seven MS patients with overlapping BV5S2 peptides spanning amino acids 1-94. Six patients responded to at least one of three overlapping or substituted CDR2 peptides possessing a core epitope of residues 44-52, and one patient also responded to a CDR1 peptide. Of the CDR2 peptides, the substituted (Y49T)BV5S2-38-58 peptide was the most immunogenic but cross-reacted with the native sequence and had the strongest binding affinity for MS-associated HLA-DR2 alleles, suggesting that position 49 is an MHC rather than a TCR contact residue. Two MS patients who did not respond to BV5S2 peptides were immunized successfully with CDR2 peptides from different BV gene families overexpressed by their MBP-specific T cells. Taken together, these results suggest that a widely active vaccine for MS might well involve a limited set of slightly modified CDR2 peptides from BV genes involved in T cell recognition of MBP.     

An 8-b 85-MS/s parallel pipeline A/D converter in 1-μm CMOS

A new architecture consisting of a time-interleaved array of pipelined analog-to-digital converters (ADCs) is presented. A prototype has been designed consisting of four switched-capacitor (S/C) multistage pipelined ADCs in parallel. Hardware cost is minimized by sharing resistor strings, bias circuitry and clock generation circuitry over the array. Digital error correction is employed to ease comparator accuracy requirements. Techniques are employed to minimize the effect of mismatches across the array. A key circuit issue is the design of a high-speed sample-and-hold (S/H) amplifier: a fully differential, mostly NMOS, non-folded-cascode operational-amplifier topology is used. An experimental chip was implemented in 1-μm CMOS and 8-b resolution at a sample rate of 85 megasamples per second (MS/s) was obtained. Signal-to-noise plus distortion (S/(N+D)) was 41 dB for an input sinusoid of 40 MHz     

Thalamic pain syndrome: anatomic and metabolic correlation

The reinnervation of cutaneous targets was studied in the rat tail after proximal lesions of all collector nerves. The distribution of immunofluorescent nerve fibres stained for calcitonin-gene-related peptide (CGRP) and substance P (SP) was examined after 110-210 days. Targets at all sites were reinnervated by CGRP-immunoreactive (IR) fibres. However, SP-IR terminals were rare, particularly distally, despite staining within subdermal nerve trunks.     

Impaired antibody diffusion within the cytoplasmic membrane-fibrous sheath interspace of the human sperm tail

Electron paramagnetic resonance has been used to investigate the effects of interaction of acetylcarnitine with cytoskeletal proteins in human erythrocyte membranes. This compound, currently in clinical trials as a potential therapeutic agent for Alzheimer's disease, caused a highly significant increase in cytoskeletal protein-protein interactions. Carnitine, the parent compound, also increased cytoskeletal protein-protein interactions, suggesting that the acetyl group is not hydrophobic enough to direct acetylcarnitine to the bilayer phase of the membrane. Consistent with this suggestion, no change in lipid order or dynamics with acetylcarnitine was observed. These results are discussed in terms of possible implications to Alzheimer's disease treatment.     

Tumour cell killing using chemically engineered antibody constructs specific for tumour cells and the complement inhibitor CD59

BACKGROUND: Although beta blockers have been used primarily to decrease unwanted perioperative hemodynamic responses, the sedative properties of these compounds might decrease anesthetic requirements. This study was designed to determine whether esmolol, a short-acting beta 1-receptor antagonist, could reduce the propofol concentration required to prevent movement at skin incision. METHODS: Sixty consenting patients were premedicated with morphine, and then propofol was delivered by computer-assisted continuous infusion along with 60% nitrous oxide. Patients were randomly divided into three groups, propofol alone, propofol plus low-dose esmolol (bolus of 0.5 mg/kg, then 50 micrograms.kg-1.min-1), and propofol plus high-dose esmolol (bolus of 1 mg/kg, then 250 micrograms.kg-1.min-1). Two venous blood samples were drawn at equilibrium. The serum propofol concentration that prevented movement to incision in 50% of patients (Cp50) was calculated by logistic regression. RESULTS: The propofol Cp50 with nitrous oxide was 3.85 micrograms/ ml. High-dose esmolol infusion was associated with a significant reduction in the Cp50 to 2.80 micrograms/ml (P < 0.04). Propofol computer-assisted continuous infusion produced stable serum concentrations with a slight positive blas. Esmolol did not alter the serum propofol concentration. No intergroup differences in heart rate or blood pressure response to intubation or incision were found. CONCLUSIONS: Esmolol significantly decreased the anesthetic requirement for skin incision. The components and mechanism of this interaction remain unclear. A simple pharmacokinetic interaction between esmolol and propofol does not explain the Cp50 reduction. These results demonstrate an anesthetic-sparing effect of a beta-adrenergic antagonist in humans under clinically relevant conditions.     

Monophosphoryl lipid A induces delayed preconditioning against cardiac ischemia-reperfusion injury

Quantitative ultrasound (QUS) bone measurement is a promising, relatively new technique for the diagnosis of osteoporosis. Unlike to the more established method of bone densitometry [measurement of bone mineral density (BMD) e.g. using dual X-ray absorptiometry (DEXA)], QUS does not use ionizing radiation. It is cheaper, takes up less space and is easier to use than densitometry techniques. The two QUS parameters currently measured are broadband ultrasound attenuation (BUA) and speed of sound (SOS). The reported age-related changes for healthy women range from -0.27% to -1.62% per year for BUA and from -0.06% to -0.19% per year for SOS. Precision ranges from 1.0 to 3.8% (CV) for BUA and from 0.19 to 0.30% (CV) for SOS. The new method of imaging ultrasound has improved the precision of QUS measurements. QUS is significantly correlated with BMD. Studies with the latest equipment have shown r-values between 0.6 and 0.9 in site-specific measurements, and QUS is thus believed to reflect mainly BMD. However, other studies indicate that QUS measures something other than the actual mineral content of bone, namely bone quality, e.g. in vitro studies have shown that QUS reflects trabecular orientation independently of BMD. In both cross-sectional and prospective studies, QUS seems to be as good a predictor of osteoporotic fractures as BMD. In two large prospective studies, QUS also predicted fracture risk independently of BMD. QUS has just begun to be used systematically for monitoring the response to anti-osteoporotic treatments in prospective trials. In the studies performed, QUS has been found to be useful in the follow-up of patients. QUS is thus a promising new technique for bone assessment.