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PubMed2006

Hypothalamic abnormalities in schizophrenia: sex effects and genetic vulnerability.

BACKGROUND: This is a unique hypothalamic magnetic resonance imaging (MRI) study in schizophrenia, an important region in the limbic system. We hypothesized abnormal volumetric increases, with greater severity in multiplex families (more than one ill member) compared with simplex families (one ill). We tested the hypothesis that normal hypothalamic sexual dimorphism is disrupted in schizophrenia. METHODS: Eighty-eight DSM-III-R schizophrenia cases (40 simplex and 48 multiplex), 43 first-degree nonpsychotic relatives, and 48 normal comparisons systematically were compared. A 1.5-Tesla General Electric scanner was used to acquire structural MRI scans, and contiguous 3.1-mm slices were used to segment anterior and posterior hypothalamus. General linear model for correlated data and generalized estimating equations were used to compare cases, relatives, and controls on right and left hypothalamus, controlled for age, sex, and total cerebral volume. Spearman's correlations of hypothalamic volumes with anxiety were calculated to begin to examine arousal correlates with structural abnormalities. RESULTS: Findings demonstrated significantly increased hypothalamic volume in cases and nonpsychotic relatives, particularly in regions of paraventricular and mammillary body nuclei, respectively. This increase was linear from simplex to multiplex cases, was positively correlated with anxiety, and had a greater propensity in women. CONCLUSIONS: Findings suggest important implications for understanding genetic vulnerability of schizophrenia and the high rate of endocrine abnormalities.

Adult↗

PubMed1998

A versatile image analysis approach for simultaneous chromosome identification and localization of FISH probes.

Modern cytogenetic techniques, such as comparative genomic hybridization (CGH) and the multi-color fluorescence in situ hybridization (FISH) techniques of multiplex fluorescence in situ hybridization (M-FISH) and spectral karyotyping (SKY), require a coordinated banding analysis to maximize their usefulness. All of the methods currently used, including Giemsa (G-) banding, Alu banding, and 4',6-diamidino-2-phenyl-indole (DAPI) banding, have serious drawbacks. A simple and effective method to band chromosomes concurrently with FISH is needed. To address this problem, we stained chromosomes with DAPI and chromomycin A3, and then used an image analysis program to generate banding by dividing the image taken with a DAPI excitation filter by the image taken with a chromomycin A3 excitation filter. The result was a metaphase spread in which the chromosomes possessed a banding pattern characteristic of R-banding. The image analysis program was then used to generate linescans of pixel intensity versus relative position along the length of chromosomes that were banded using this technique, which we have called D/C R-banding. Each chromosome in a genome was represented by a characteristic scan profile, which was unaffected by FISH signals. Reference linescans were prepared by karyotyping D/C R-banded chromosomes for a given species, and then drawing lines along the length of the known chromosomes. The linescans were combined into a spreadsheet database, which was linked by dynamic data exchange to the image analysis program and normalized for length and intensity. The linescan of an unknown chromosome was then transferred to the spreadsheet, where it was normalized for length and intensity and overlaid on the linescans of each chromosome in the genome. Unknown chromosomes were identified by comparison of their graphs with graphs in the standardized reference genome. We have used this approach to create reference linescan karyotypes of several species, and to identify chromosomes on which FISH was performed.

Animals↗

PubMed1993

A stationary hemispherical SPECT imager for three-dimensional brain imaging.

A completely stationary, hemispherical-coded aperture SPECT imaging system was designed to produce three-dimensional images of the brain. The system consisted of a hemispherical multiple-pinhole coded aperture and 20 small (100 x 100 mm crystal area) digital gamma cameras. Reconstructions and measured performance specifications from two laboratory versions of the imager are presented. The reconstructed field of view of these systems was an ellipsoidal region with semi-diameters of 100 x 100 x 50 mm. The reconstructed spatial resolution for a point source in air at the center of this field was found to be 4.8 mm FWHM and the corresponding system sensitivity was 36 cps/microCi. An analysis using an ideal-observer model indicated that the multiplexed projection data suffered a 21% degradation relative to similar, but nonmultiplexed SPECT data. Therefore, by this measure, the effective sensitivity of the brain imager was 79% of the measured value.

Brain↗

PubMed2004

Use of the DNA flow-thru chip, a three-dimensional biochip, for typing and subtyping of influenza viruses.

Influenza A viruses, which are further subtyped on the basis of antigenic differences in external hemagglutinin and neuraminidase glycoproteins, and influenza B viruses are prominent among the viral causes of respiratory diseases and can cause a wide spectrum of illness. Each year these viruses are responsible for recurrent epidemics, frequently in association with genetic variation. There is a requirement for sensitive and rapid diagnostic techniques in order to improve both the diagnosis of infections and the quality of surveillance systems. A new three-dimensional biochip platform (Flow-Thru Chip; MetriGenix) was used to develop a rapid and reliable molecular method for the typing and subtyping of influenza viruses. Oligonucleotide probes immobilized in microchannels of a silicon wafer were selected to recognize multiple fragments of the influenza A virus matrix protein gene; the influenza B virus NS gene; the H1, H3, and H5 hemagglutinin genes; and the N1 and N2 neuraminidase genes. Biotinylated amplicons resulting from either multiplex or random reverse transcription-PCR were hybridized to arrayed oligonucleotides on the influenza virus chip before they were stained with horseradish peroxidase-streptavidin and were imaged by use of a chemiluminescent substrate. The chip analysis procedure, from the time of pipetting of the sample into the chip cartridge to the time of analysis of the results, was performed in less than 5 h. The random PCR exhibited a higher level of performance than the multiplex PCR in terms of the specificity of product hybridization to the influenza virus chip. Analysis of influenza A viruses (H1N1, H3N2, H1N2, and H5N1) and influenza B viruses showed that this microarray-based method is capable of the rapid and unambiguous identification of all types and subtypes of viruses by use of random PCR products. The redundancy of the probes designed for each gene selected yielded an additional criterion of confidence for the subtyping of viruses which are known for antigenic variations in some of their components.

Base Sequence↗

PubMed1997

[A case of rapidly progressive T cell type malignant lymphoma which started with multiple cranial neuropathy].

A 35-year-old man had suffered from recurrent right trigeminal nerve palsy and flaccid paraparesis for about five months. Cerebrospinal fluid (CSF) showed a marked increase of protein (400 mg/dl) and mononuclear cells (146/mm3), but there were no malignant cells. Antibiotic therapy remitted his inguinal and mediastinal lymph nodes swelling, and trigeminal nerve palsy had recovered spontaneously. Then he developed left trigeminal and facial nerve palsy, mononeuropathy multiplex, and cauda equina syndrome. Nerve conduction studies revealed delayed velocity and reduction of amplitude. Enhanced magnetic resonance imaging showed increased signal intensity in bilateral trigeminal nerves, left internal auditory meatus, and meninges of the basal cistern. Also, there were two mass lesions in cauda equina. They were operated by orthopedist, and were not malignant. After that, CSF cells of malignant lymphoma were elevated and revealed T cell type (large cell). Then the patient exacerbated in bulbar palsy and died. When there is lymph node swelling with multiple neurological deficits, despite remission of lesions and signs, biopsies should be positively pursued early in the patient's clinical course.

Adult↗

PubMed1993

Scintigraphy versus pH probe for quantification of pediatric gastroesophageal reflux: a study using concurrent multiplexed data and acid feedings.

We performed 12 simultaneous scintigraphic and pH probe studies in children being evaluated for reflux to determine the ability of scintigraphic images in comparison to pH probe data to quantify gastroesophageal reflux in children and to identify an optimal scintigraphic framing interval. We used a multiplexor to synchronize exactly the scintigraphy and pH probe and an acid meal to avoid missing postprandial episodes with the pH probe. We reformatted the studies in both 60-sec and 10-sec images to compare the two framing intervals. The 60-sec images produced better agreement between pH probe and scintigraphy than the 10-sec images for both the number of reflux episodes and the duration of reflux. Of the 64 reflux episodes detected by either method at this coarser framing interval, scintigraphy detected 80%, the pH probe detected 63% and both methods concurrently detected 42%. Of the 681 60-sec images aggregated across patients, scintigraphy detected 55% of those with intraesophageal refluxate, the pH probe detected 96% and both tests concurrently detected 51%. Within patients, the number of positive scintigraphic images in the postprandial hour correlated with the number of images with pH < 4 during the same hour (p = 0.008, and p < 0.0001 if two patients with very rapid gastric emptying are excluded), but not with the results of the 24-hr pH probe study. A 1-hr scintigraphic study formatted in 60-sec frames provides a quantitative representation of postprandial gastroesophageal reflux for children, particularly if they do not have rapid gastric emptying.

Child↗

PubMed1984

Two algorithms for use with an orthogonal-view coded-aperture system.

ohe goal of single photon emission computerized tomography is to map out a three-dimensional distribution of a radionuclide that is concentrated in a structure of interest. There are a number of imaging modalities that achieve this goal with varying degrees of success. In this study, computer simulation is used to explore a novel imaging modality, orthogonal-view coded-aperture imaging. Furthermore, a comparison is made between two reconstruction algorithms, one being an iterative back-projection algorithm and the other a Monte Carlo algorithm. Finally, evidence is presented suggesting that a deficiency in the projection data due to multiplexing is less disturbing than that due to limited angular range.

Evaluation Studies as Topic↗

PubMed1993

Monitoring the patient's EEG during echo planar MRI.

The recording of an EEG while the patient is undergoing magnetic resonance imaging (MRI) data acquisition, as far as we are aware, has not been previously accomplished. By careful selection and arrangement of analog multiplexed cable-telemetry equipment to eliminate both ferrous and RF sources, a stable, readable EEG can be obtained without interfering with the diagnostic quality of the MRI. This arrangement does not cause localized heating or burning at the electrode sites. This technical capability permits more accurate neurophysiological control during the acquisition of echo planar functional MRI studies as well as providing indications of anatomical localization of electrical sources.

Echo-Planar Imaging↗

PubMed2000

Reconstruction of two- and three-dimensional images from synthetic-collimator data.

A novel SPECT collimation method, termed the synthetic collimator, is proposed. The synthetic collimator employs a multiple-pinhole aperture and a high-resolution detector. The problem of multiplexing, normally associated with multiple pinholes, is reduced by obtaining projections at a number of pinhole-detector distances. Projections with little multiplexing are collected at small pinhole-detector distances and high-resolution projections are collected at greater pinhole-detector distances. These projections are then reconstructed using the ML-EM algorithm. It is demonstrated through computer simulations that the synthetic collimator has superior resolution properties to a high-resolution parallel-beam (HRPB) collimator and a specially built ultra-high-resolution parallel-beam (UHRPB) collimator designed for our 0.38-mm pixel CdZnTe detectors. It is also shown that reconstructing images in three dimensions is superior to reconstructing them in two dimensions. The advantages of a high-resolution synthetic collimator over the parallel-hole collimators are apparently reduced in the presence of statistical noise. However, a high-sensitivity synthetic collimator was designed which again shows superior properties to the parallel-hole collimators. Finally, it is demonstrated that, for the cases studied, high-resolution detectors are necessary for the proper functionality of the synthetic collimator.

Algorithms↗

PubMed2005

Recovering real-world images from single-scale boundaries with a novel filling-in architecture.

Filling-in models were successful in predicting psychophysical data for brightness perception. Nevertheless, their suitability for real-world image processing has never been examined. A unified architecture for both predicting psychophysical data and real-world image processing would constitute a powerful theory for early visual information processing. As a first contribution of the present paper, we identified three principal problems with current filling-in architectures, which hamper the goal of having such a unified architecture. To overcome these problems we propose an advance to filling-in theory, called BEATS filling-in, which is based on a novel nonlinear diffusion operator. BEATS filling-in furthermore introduces novel boundary structures. We compare, by means of simulation studies with real-world images, the performance of BEATS filling-in with the recently proposed confidence-based filling-in. As a second contribution we propose a novel mechanism for encoding luminance information in contrast responses ('multiplex contrasts'), which is based on recent neurophysiological findings. Again, by simulations, we show that 'multiplex contrasts' at a single, high-resolution filter scale are sufficient for recovering absolute luminance levels. Hence, 'multiplex contrasts' represent a novel theory addressing how the brain encodes and decodes luminance information.

Computer Simulation↗

PubMed1995

Linkage analysis with multiplexed short tandem repeat polymorphisms using infrared fluorescence and M13 tailed primers.

The use of short tandem repeat polymorphisms (STRPs) as marker loci for linkage analysis is becoming increasingly important due to their large numbers in the human genome and their high degree of polymorphism. Fluorescence-based detection of the STRP pattern with an automated DNA sequencer has improved the efficiency of this technique by eliminating the need for radioactivity and producing a digitized autoradiogram-like image that can be used for computer analysis. In an effort to simplify the procedure and to reduce the cost of fluorescence STRP analysis, we have developed a technique known as multiplexing STRPs with tailed primers (MSTP) using primers that have a 19-bp extension, identical to the sequence of an M13 sequencing primer, on the 5' end of the forward primer in conjunction with multiplexing several primer pairs in a single polymerase chain reaction (PCR) amplification. The banding pattern is detected with the addition of the M13 primer-dye conjugate as the sole primer conjugated to the fluorescent dye, eliminating the need for direct conjugation of the infrared fluorescent dye to the STRP primers. The use of MSTP for linkage analysis greatly reduces the number of PCR reactions. Up to five primer pairs can be multiplexed together in the same reaction. At present, a set of 148 STRP markers spaced at an average genetic distance of 28 cM throughout the autosomal genome can be analyzed in 37 sets of multiplexed amplification reactions. We have automated the analysis of these patterns for linkage using software that both detects the STRP banding pattern and determines their sizes. This information can then be exported in a user-defined format from a database manager for linkage analysis.

Chromosome Mapping↗

PubMed2006

Visual DNA microarrays for simultaneous detection of Ureaplasma urealyticum and Chlamydia trachomatis coupled with multiplex asymmetrical PCR.

Visual DNA microarrays, based on gold label silver stain (GLSS) and coupled with multiplex asymmetrical PCR, were developed for simultaneous, sensitive and specific detection of Ureaplasma urealyticum and Chlamydia trachomatis. 5'-end-amino-modified oligonucleotides, which were immobilized on glass surface, acted as capturing probes that were designed to bind complementary biotinylated targets DNA. The gold-conjugated streptavidins were introduced to the microarray for specific binding to biotin. The black image of microarray spots, resulting from the precipitation of silver onto nanogold particles bound to streptavidins, were used to detect biotinylated targets DNA visually or with a visible light scanner. Multiplex asymmetrical PCR of U. urealyticum, C. trachomatis and Bacillus subtilis (used as positive control) was performed to prepare abundant biotinylated single-stranded targets DNA, which affected detection efficiency and sensitivity of hybridization on microarray. Plenty of clinical samples of U. urealyticum and C. trachomatis from infected patients were tested using home-made DNA microarrays. For its high sensitivity, good specificity, simplicity, cheapness and speed, the present visual gene-detecting technique has potential applications in clinical fields.

Biosensing Techniques↗

PubMed2006

Paraneoplastic mononeuritis multiplex in non-small-cell lung carcinoma.

A 60-year-old man developed two selective peripheral mononeuropathies of the peroneal and later the radial nerve, shortly after a diagnosis of large-cell lung carcinoma. Nerve conduction studies and electromyography confirmed isolated lesions in both nerves, and in the case of the peroneal nerve lesion, focal conduction block was localised to the level of the fibula neck. Subsequent magnetic resonance imaging of the lower limb excluded focal compression or malignant infiltration along the course of the peroneal nerve, and there was no signal change within the nerve, prompting a diagnosis of paraneoplastic mononeuritis multiplex. Anti-neuronal antibodies and serological markers of systemic vasculitis were negative. Neither the patient's large-cell lung carcinoma nor mononeuritis multiplex responded to chemotherapy, and he died within 6 months of the initial diagnosis.

Carcinoma, Non-Small-Cell Lung↗

PubMed1987

Layout of a multiplexed electrode VLSI circuit for monitoring evoked responses in cerebral cortex.

This paper summarizes the details of the design of an integrated circuit layout usable as a multiple-electrode implantable cerebral cortex sensor. The purpose of implanting multiplexed electrode circuits in a cerebral cortex is to monitor the electroencephalograph (EEG) and visual evoked response (VER) generated while the subject performs normal visual functions. A summary of the human image processing system is given as a background for the circuit design work. A typical subject for the research would be a laboratory animal. External power, clocking, and analogue data lines required for its operation posed problems for the original electrode chip. The second generation brain chip includes self contained-power with on-board multiplexing and clocking circuits. The most significant improvement is the incorporation of analogue to digital (A/D) converters. Through the use of A/D converters, brain signal data can be converted at the site of implant, eliminating induced noise from analogue wires used on the original chip. Conversion at the implant site, the primary visual cortex, yields a more accurate indication of the actual brain data.

Cerebral Cortex↗

PubMed2001

Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules.

Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots (zinc sulfide-capped cadmium selenide nanocrystals) into polymeric microbeads at precisely controlled ratios. Their novel optical properties (e.g., size-tunable emission and simultaneous excitation) render these highly luminescent quantum dots (QDs) ideal fluorophores for wavelength-and-intensity multiplexing. The use of 10 intensity levels and 6 colors could theoretically code one million nucleic acid or protein sequences. Imaging and spectroscopic measurements indicate that the QD-tagged beads are highly uniform and reproducible, yielding bead identification accuracies as high as 99.99% under favorable conditions. DNA hybridization studies demonstrate that the coding and target signals can be simultaneously read at the single-bead level. This spectral coding technology is expected to open new opportunities in gene expression studies, high-throughput screening, and medical diagnostics.

Biotechnology↗

PubMed2001

High-throughput AFLP analysis using infrared dye-labeled primers and an automated DNA sequencer.

Amplified fragment length polymorphism (AFLP) analysis is currently the most powerful and efficient technique for the generation of large numbers of anonymous DNA markers in plant and animal genomes. We have developed a protocol for high-throughput AFLP analysis that allows up to 70,000 polymorphic marker genotype determinations per week on a single automated DNA sequencer. This throughput is based on multiplexed PCR amplification of AFLP fragments using two different infrared dyelabeled primer combinations. The multiplexed AFLPs are resolved on a two-dye, model 4200 LI-COR automated DNA sequencer, and the digital images are scored using semi-automated scoring software specifically designed for complex AFLP banding patterns (AFLP-Quantar). Throughput is enhanced by using high-quality genomic DNA templates obtained by a 96-well DNA isolation procedure.

Electrophoresis↗

PubMed1994

Allergic granulomatosis and angiitis (Churg-Strauss syndrome) presenting as prominent neurologic lesions and optic neuritis.

We describe a Chinese male patient with clinicopathologically definite Churg-Strauss syndrome. He had a clinical pattern of mononeuropathy multiplex and unusual optic neuritis, the latter probably being due to vasculitis related demyelination of the optic nerve. Magnetic resonance imaging of the brain revealed many clinically silent central nervous system lesions. He initially received steroid therapy, but an early cessation of treatment resulted in acute exacerbation. Later on, he was treated with combined prednisolone-cyclophosphamide therapy for 1 year. His ophthalmological and neurological symptoms responded well to such a regimen and disappeared within 6 months.

Adult↗

PubMed1987

The Sheffield data collection system.

Because of the intrinsically low sensitivity of any surface potential measurement to resistivity changes within a volume conductor, any data collection system for impedance imaging must be sensitive to changes in the peripheral potential profile of the order of 0.1%. For example, whilst the resistivity changes associated with lung ventilation and the movement of blood during the cardiac cycle range from 3 to 100% the changes recorded at the surface are very much less than this. The Sheffield data collection system uses 16 electrodes which are addressed through 4 multiplexers. Overall system accuracy is largely determined by the front-end equivalent circuit which is considered in some detail. This equivalent circuit must take into account wiring and multiplexer capacitances. A current drive of 5 mA p-p at 5 kHz is multiplexed to adjacent pairs of electrodes and peripheral potential profiles are recorded by serially stepping around adjacent electrode pairs. The existing Sheffield system collects the 208 data points for one image in 79 ms and offers 10 image data sets per second to the microprocessor. For a homogeneous circular conductor the ratio of the maximum to minimum signals within each peripheral potential profile is 45:1. The temptation to increase the number of electrodes in order to improve resolution is great and an achievable performance for 128 electrodes is given. However, any improvement in spatial resolution can only be made at the expense of speed and sensitivity which may well be the more important factors in determining the clinical utility of APT.

Amplifiers, Electronic↗