Implantable biomedical microsystems for neural prostheses.

In the following article, the technologies to fabricate polyimide-based thin and flexible substrates with monolithically integrated electrode arrays and printed circuit boards (PCB) for hybrid electronic assemblies as well as an assembling technique that connects bare electronic dice with flexible PCBs are presented. The concept of modular, flexible biomedical microsystems as neural prostheses is introduced in general and described in detail in three examples. A cuff electrode with integrated multiplexer circuitry and standard implantable cables represents the combination of microtechnology with precision mechanics; a sieve electrode used as an implant in peripheral nerve regeneration studies demonstrates the next level of integration density but still uses a cable connection; and last, joint effort to fabricate the demonstrator of a vision prosthesis that is completely implantable in the eye with a wireless link for energy supply and data transmission is presented. System design, hybrid assembling technology, and flexible multilayer encapsulation using parylene and silicone rubber are the key components for creating a new generation of neural prostheses for complex and challenging new applications.     

V. Yeast sequencing reports. Identification of a gene encoding a new Ypt/Rab-like monomeric G-protein in Saccharomyces cerevisiae

A Saccharomyces cerevisiae sequence cloned by serendipity was found to encode a protein that is a new member of the Ypt/Rab monomeric G-protein family. This sequence shows high homology to the yeast genes SEC4 and YPT1 and, like SEC4 and YPT1, is essential for viability. The sequence was localized to chromosome V based upon hybridization to pulse-field gel-separated yeast chromosomes. The sequence has been deposited in the GenBank data library under Accession Number L17070.     

Fluorescence flow cytometry of human leukocytes in the detection of LDL receptor defects in the differential diagnosis of hypercholesterolemia

A flow-cytometric method with fluorescence-labeled monoclonal antibodies (MABs) against the low density lipoprotein (LDL) receptor (C7A MAB) or 3,3'-dioctadecylindocarbocyanin-iodide (DiI) LDL has been developed that allows the quantification of LDL receptors on leukocytes and the identification of patients with familial hypercholesterolemia (FH) within 48 hours. Leukocytes were isolated from 10 mL anticoagulated blood by density gradient centrifugation. To induce maximal expression of LDL receptors, mononuclear cells were preincubated with either phytohemagglutinine (PHA) or lipoprotein-deficient serum (LPDS). LPDS-treated monocytes provided a more homogeneous cell population with regard to LDL receptor activity than did the PHA-treated lymphocytes; they also provided a greater discrimination between the fluorescence of the receptor probes and cellular autofluorescence. The C7A MAB was able to compete for DiI LDL binding by about 40%. In competition with unlabeled LDL, DiI LDL revealed linear binding, indicating an affinity similar to native LDL. The binding characteristics of DiI LDL were also similar to 125I-LDL binding. LDL isolated from familial defective apolipoprotein B-100 was not able to compete for DiI LDL binding on monocytes, whereas native LDL reduced it by about 80%. In monocytes from FH heterozygous patients, the cellular mean fluorescence using either C7A MAB or DiI LDL at 4 degrees C was 30% to 70%; in FH homozygotes, cellular mean fluorescence was less than 20% of that in monocytes from normal individuals. In patients with familial defective apolipoprotein B-100 antibody binding was normal, but one patient's own LDL failed to compete with normal DiI LDL for 4 degrees C binding on U937 test monocytes. Patient monocytes having internalization defects showed normal 4 degrees C DiI LDL binding, but at 20 degrees C cell-associated fluorescence was reduced by about 40%. In our study 384 hypercholesterolemic patients (preselected according to serum cholesterol levels, clinical symptoms, and family history) were analyzed for LDL receptor expression using the C7A MAB-based assay. In 71.8% of the patients with cholesterol levels higher than 300 mg/dL, an LDL receptor deficiency was observed. Apolipoprotein E isoforms and lipoprotein[a] were found to be independent from the LDL receptor status. In some patients with high cholesterol levels but normal LDL receptor expression with the C7A MAB assay, LDL receptor defects could be diagnosed when either reduced binding or internalization of DiI LDL or familial defective apolipoprotein B-100 was detected.(ABSTRACT TRUNCATED AT 400 WORDS)     

As number of patients grows, so do critical problems facing MDs who provide dialysis

The growth in the number of dialysis patients in Canada is causing a critical shortage of resources. The low transplantation rate and an increase in the number of patients, combined with insufficient funding to expand facilities, threatens access to the expensive but life-sustaining therapy. Michel Martin, who recently underwent a kidney transplant, looks at the situation facing dialysis patients in Quebec and Ontario.     

MRT of experimental liver abscesses: a comparison of a new blood pool contrast medium with gadolinium-DTPA in animal experiments

PURPOSE: In an experimental pyogenic liver abscess model, the signal intensities were compared intraindividually and interindividually after the application of a new blood pool contrast agent, 24-gadolinium-DTPA (diethylenetriamine-pentaacetic acid) cascade polymer, and after the application of gadopentetate dimeglumine. METHODS: In 20 rabbits with experimentally induced liver abscesses, the relative signal intensities of the liver, abscess centre, abscess wall and portal vein were assessed before and between 30 seconds and 60 minutes after injection of a 25 mumol/kg dose of gadolinium polymer and of 100 mumol/kg of gadolinium-DTPA, respectively. Measurements were performed at 1.5 Tesla, using a head coil and a Flash-2-D sequence. RESULTS: The interindividual comparison (unpaired T-test, p < 0.05) yielded significant differences of the relative signal intensities of the abscess centre (at any time point after contrast-media application), abscess wall (between 15 and 60 minutes after contrast media application), and portal vein (between 30 seconds and 7.5 minutes after contrast media application). The interindividual comparison showed a significantly higher abscess centre-liver contrast (between 30 seconds and 12.5 minutes after contrast media application) and a significantly higher abscess wall-centre contrast (between two and 7.5 minutes after contrast media application) after the application of gadolinium polymer compared with gadopentetate dimeglumine. CONCLUSION: In this animal model, the higher abscess centre-liver contrast after the application of gadolinium polymer was the basis for a better and prolonged visibility of the abscesses, as compared with images acquired after injection of gadopentetate dimeglumine.     

Surface leakage currents in SiN/sub x/ passivated AlGaN/GaN HFETs

A novel guarded surface leakage test structure is used to isolate the surface and bulk leakage contributions to gate current in AlGaN/GaN HFETs. Passivation with various recipes of SiN/sub x/ always resulted in the commonly observed increase in gate leakage, which was found to be dominated by bulk leakage through the AlGaN. However, high temperature deposited SiN/sub x/ recipes gave a 1-2 orders reduction in surface leakage, whereas low temperature deposition gave an increase. Gate lag measurements were found to correlate closely with the surface leakage component, giving direct evidence that the key device problem of current slump is associated with current flow at the AlGaN surface.