Differential effects of kindling and kindled seizures on place learning in the morris water maze

There is some controversy about the role of long-term potentiation (LTP) in spatial learning. The authors have found that triggering generalized kindled seizures with stimulation of the perforant path disrupts spatial learning in the Morris water maze but that kindling per se does not affect spatial learning. It is suggested that abnormal electrical activity induced by high-frequency stimulation of the perforant path may have been responsible for the disruption of spatial learning previously attributed to LTP saturation.     

Analysis of pressure waves as a mean of diagnosing vascular obstructions

A feasibility study was made to examine whether pressure measurements can be used to diagnose vascular obstructions in blood vessels. Distortion of a pressure wave due to an obstruction in an elastic tube was investigated theoretically and experimentally. Linear theory and the method of characteristics were employed in developing mathematical expressions for the distortion of the pressure wave. The quality of the models developed was examined by performing experiments on a latex tube with rigid obstructions. A nonlinear model using the method of characteristics was in good agreement with the experiment data for obstructions with any severity, while a linear model was applicable to small obstructions. The nonlinear model is proposed as a mathematical model for the detection of vascular obstructions by analysing pressure waves.     

An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates.

The long half-life and stability of human serum albumin (HSA) make it an attractive candidate for fusion to short-lived therapeutic proteins. Albuferon (Human Genome Sciences [HGS], Inc., Rockville, MD) beta is a novel recombinant protein derived from a gene fusion of interferon-beta (IFN-beta ) and HSA. In vitro, Albuferon beta displays antiviral and antiproliferative activities and triggers the IFN-stimulated response element (ISRE) signal transduction pathway. Array analysis of 5694 independent genes in Daudi-treated cells revealed that Albuferon beta and IFN-beta induce the expression of an identical set of 30 genes, including 9 previously not identified. In rhesus monkeys administered a dose of 50 microg/kg intravenously (i.v.) or subcutaneously (s.c.) or 300 microg/kg s.c., Albuferon beta demonstrated favorable pharmacokinetic properties. Subcutaneous bioavailability was 87%, plasma clearance at 4.7-5.7 ml/h/kg was approximately 140-fold lower than that of IFN-beta, and the terminal half-life was 36-40 h compared with 8 h for IFN-beta. Importantly, Albuferon beta induced sustained increases in serum neopterin levels and 2',5' mRNA expression. At a molar dose equivalent to one-half the dose of IFN-beta, Albuferon beta elicited comparable neopterin responses and significantly higher 2',5'-OAS mRNA levels in rhesus monkeys. The enhanced in vivo pharmacologic properties of IFN-beta when fused to serum albumin suggest a clinical opportunity for improved IFN-beta therapy.     

In vitro velocity measurements down strem from the lonescu-Shiley aortic bioprosthesis in steady and pulsatile flow

Velocity measurements were made in vitro using laser Doppler anemometry (LDA) downstream from an lonescu-Shiley (IS) bioprosthetic aortic heart valve. Velocity measurements were made in both steady and pulsatile flow. A systematic, flow mapping approach to the measurement methodology showed that the IS valve generated a large jetlike flow constriction. The acceleration ratio, defined as the maximum mean velocity for the IS valve divided by that for no valve obstructing the flow, was as high as 2·4 for steady flow and 2·6 for pulsatile flow. It was concluded that the IS valve generated a flow quite unlike that observed by other in vestigators for the natural human aortic valve, after which the leaflet design of the IS valve was modelled. In addition, a comparative analysis of steady and pulsatile results was undertaken. It was found that the pulsatile flow results for the systolic ejection interval could be divided into three phases, denoted early, mid, and late systole, as defined by the flow structure at the data plane location. Only during midsystole were the pulsatile flow results approximated by the steady flow results. Also, it was found that the magnitude of the flow disturbance measured in steady flow tended to be an upper bound on that measured for pulsatile flow.     

A quantitative method for thein vitro study of sounds produced by prosthetic aortic heart valves Part II: an experimental,comparative study of the sounds produced by a normal and simulated-abnormal Starr-Edwards series 2400 aortic prosthesis

A comparative study was made of the sounds produced by a normal Starr-Edwards 2400 aortic valve prosthesis with those produced by the same valve but having a simulated overgrowth at the apex of the struts. Comparisons were made over the entire cardiac cycle for time and amplitude, power-density spectra, power-distribution spectra, power-distribution surfaces associated with individual valves, and three-dimensional power-distribution-difference surface. Power-density spectra were compared for portions of the cycle corresponding to the opening, systolic, and closing sounds of the valve. Physical parameters of an acoustical model were estimated from the power-density spectra. The results showed that each comparison gave information pertinent to the simulated malfunction. Opening. systolic and closing sounds, respectively, were different for each valve. The opening sound of the abnormal valve displayed a much lower frequency. Systolic sounds for the two valves were similar in frequency, but the normal valve produced more total power for this sound. The closing sound of the abnormal valve occurred later than that of the normal valve. These differences were more clearly seen when viewed in the frequency domain.     

High-sensitivity PCR detection of parvovirus B19 in plasma

Parvovirus B19 (B19) is a human pathogen transmitted to susceptible individuals via respiratory secretions and contaminated blood or blood products. B19 levels in pooled plasma of less than 10(4) genome equivalents/ml may not be infectious, while those greater than 10(7)/ml are capable of transmitting infection. A World Health Organization (WHO) B19 DNA international standard has been recently introduced. The purpose of the present work was to develop a PCR-enzyme-linked immunosorbent assay (PCR-ELISA) calibrated against the WHO B19 DNA international standard which could easily and reliably detect B19 DNA levels in plasma above 10(4) IU/ml (6.5 x 10(3) genome equivalents/ml). A B19 PCR-ELISA system was developed which uses a dinitrophenylated oligonucleotide probe to detect immobilized biotinylated amplicons following single-round PCR amplification. The level of B19 DNA (in international units per milliliter) in individual and pooled plasma specimens was evaluated. Proteinase K treatment of plasma was found to be sufficient to quantitatively release B19 DNA. The B19 PCR-ELISA had a sensitivity of detection of 1.6 x 10(3) IU/ml B19 DNA and a dynamic range extending from 8 to 1,000 IU of B19 DNA (equivalent to 1.6 x 10(3) to 2 x 10(5) IU of B19 DNA/ml). Furthermore, the antibody profile of pooled plasma products was determined in terms of B19 immunoglobulin G (IgG) (in international units per milliliter). The B19 IgG level was found to be 64.7 +/- 17.5 IU/ml (mean +/- standard deviation). The B19 PCR-ELISA, which is calibrated against the B19 DNA international standard, may have an application for the rapid screening of plasma minipools for B19 DNA, thereby leading to an improvement in blood product safety.