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PubMed2001

Ataxia and peripheral neuropathy: rare manifestations in Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is a multisystemic vasculitis. Nervous system involvement is usually underestimated. Headaches, mental status changes and seizures are the most frequent neurologic symptoms. Ataxia and mononeuropathy are both very rare. We present an 11-year-old boy with HSP who suffered from ataxia during the initial presentation and peripheral neuropathy at the time of a relapse. Brainstem vasculitic involvement was shown by magnetic resonance imaging, while cranial tomography was normal. All the neurologic symptoms and signs resolved following bolus methylprednisolone administration. Ten months later he had a second course of HSP with skin and renal involvement. A percutaneous renal biopsy, which was performed due to persistent hematuria, revealed mesangial proliferation with IgA deposition. During that period the patient experienced pain and numbness in the right foot and leg; electromyography showed signs of mononeuritis multiplex involving the right posterior tibial nerve. The patient responded to steroid therapy.

Ataxia↗
PubMed1991

Discordance of T-cell receptor beta-chain genes in familial multiple sclerosis.

Restriction fragment length polymorphisms of the T-cell receptor beta-chain gene were studied in DNA obtained from 96 individuals from 14 multiplex families with multiple sclerosis (MS). Thirty-four family members had definite MS and two had probable MS. Five normal family members had abnormal findings on cranial magnetic resonance imaging (MRI) scans. Linkage analysis was performed using the BglII and the KpnI polymorphisms. With penetrance values from 0.1 to 0.7, and altering the scoring of the normal individuals with abnormal findings on MRI scans from "unknown" to "affected," log of the odds scores between -4.59 to -12.76 were found for the autosomal dominant model. For the autosomal recessive model with a penetrance range from 0.1 to 1.0, the LOD scores ranged from -8.20 to -32.98. These findings do not support a direct role of T-cell receptor beta-chain gene in the inheritance of MS.

Alleles↗
PubMed2003

Superresolution by use of code division multiplexing.

Traditional methods for superresolution have sacrificed field of view for resolution. These methods multiplexed different parts of signals' spectrum on different carriers, and thus managed to transfer a wider range of frequency, in a manner that is similar to frequency division multiplexing in classical communication. We propose code division multiplexing for such an application, which has been shown to have superior capabilities. To enable such mutiplexing we propose a unique setup that creates an incoherent cosine transform of the image. A theoretical analysis of the setup is obtained and later compared with the empirical results.

Journal Article↗
PubMed2003

Development of protein microarray technology to monitor biomarkers of rheumatoid arthritis disease.

Most biological processes are mediated by complex networks of molecular interactions involving proteins. The analysis of protein expression in biological samples is especially important in the identification and monitoring of biomarkers for disease progression and therapeutic endpoints. In this paper, the development of a protein microarray format for multiplexed quantitative analysis of several potential markers for rheumatoid arthritis (RA) is described. Development of a high-performance protein microarray system depends on several key parameters such as surface chemistry, capture agents, immobilization technology, and methods used for signal detection and quantification. Several technical possibilities were investigated and compared: poly-L-lysine versus self-assembled monolayer of octadecyl phosphoric acid ester for surface chemistries; noncontact piezoelectric versus contact printing technology for antibody deposition; CCD camera capture versus fluorescent scanning for image detection; and the concentration of coating antibody. On the basis of reproducibility, signal-to-noise ratio, and sensitivity we have selected self-assembled monolayer, noncontact piezoelectric printer, and high-read-out fluorescence scanning for our microarray format. This format was used to perform multiplexed quantitative analysis of several potential markers of disease progression of rheumatoid arthritis: IL-1beta, IL-6, IL-8, MCP-1, and SAA. Some assays, such as MCP-1, provided a working range that covered physiologically relevant concentrations. Other assays, such as IL-6 and SAA, lacked sensitivity or were too sensitive for measuring biological concentrations, respectively. The results described demonstrate the applicability of protein microarrays to monitor RA markers; however, sandwich assay methodologies need to be further optimized to measure the appropriate biological ranges of these markers on one chip.

Arthritis, Rheumatoid↗
PubMed2002

Clinical features and neuroradiological findings of mitochondrial pathology in six neonates.

OBJECTS: We hoped to itemize the clinical and neuroradiological features of six neonates with mitochondrial disorders. METHODS: We examined a case series of six neonates. The diagnosis of mitochondrial cytopathy was made on the basis of spectrophotometric measurements of respiratory chain enzyme activities in skeletal muscle biopsy specimens. Magnetic resonance (MR) imaging was performed in all cases. CONCLUSIONS: The antenatal onset in five cases and the lack of any symptom-free interval are suggestive of fetal expression of the disease. No specific symptoms were found: arthrogryposis congenita multiplex in one, progressive hepatocellular dysfunction in three, encephalomyelopathy and cardiomyopathy in four. Complex I deficiency was found in three patients, while one patients had a defect of complex IV and the last a combined defect of complexes I and IV. Neuroradiological findings were either cerebral atrophy or white matter abnormalities of the brain stem in all cases but one and gave additional information, because clinical symptoms are not quite specific. The combination of clinical and MRI findings in neonatal cases can rule out hypoxic ischemic encephalopathy, which suggests an additional screening method to look for mitochondrial disorder.

Brain↗
PubMed1997

The Maudsley Family Study. I: Structural brain changes on magnetic resonance imaging in familial schizophrenia.

1. The authors investigated the prevalence of qualitatively rated structural brain abnormalities in schizophrenic probands and their first-degree relatives from families multiply affected with schizophrenia. 2. Magnetic resonance imaging was used to evaluate brain morphology in 33 schizophrenic probands, 54 of their non-schizophrenic first-degree relatives (including 11 presumed obligate carriers) and 37 unrelated control subjects. Structural images were examined by a neuroradiologist who was blind to diagnostic and family status. 3. 52% of the schizophrenic subjects were rated as showing abnormalities compared with 27% of presumed obligate carriers, 16% of their non-schizophrenic relatives and 11% of unrelated controls. 4. Brain abnormalities were more frequent in schizophrenic subjects from multiplex families than in their first-degree relatives and controls. Abnormalities were also found in unaffected relatives particularly those who appear to be transmitting the disorder.

Adult↗
PubMed2026

Downregulation of Trpv4 and Klf2 in brain microvessels is associated with the progression of neurovascular dysfunction and cognitive impairment in a model of heart failure with preserved ejection fraction.

Vascular cognitive impairment (VCI) shares major risk factors with heart failure with preserved ejection fraction (HFpEF), including obesity, diabetes and hypertension. Yet VCI research often relies on single-stimulus models, whereas patients experience combined risk factors. We therefore assessed cerebrovascular and cognitive phenotypes in an HFpEF model and investigated underlying mechanisms. Male Lean and Obese ZSF1 rats underwent longitudinal assessments of blood pressure, glucose, cardiac function and behavioural performance. Cerebral blood flow and neurovascular coupling were assessed by laser speckle contrast imaging. White matter integrity, blood-brain barrier (BBB) permeability and vascular density were analyzed by (immuno)histochemistry. Cortical microvessels were isolated for transcriptomic profiling, and selected targets were validated using multiplex in-situ hybridization. Obese rats exhibited neurovascular uncoupling and impaired short- and long-term memory and spatial learning, accompanied by brain atrophy and reduced myelin. BBB permeability increased at 22-23 weeks and vascular density at 34-35 weeks in Obese versus Lean rats. Transcriptomic analysis of brain microvessels revealed altered processes related to angiogenesis, vasoreactivity, immune mechanisms and vascular remodelling, with consistent downregulation of Trpv4 and Klf2. Obese ZSF1 rats develop progressive neurovascular dysfunction associated with HFpEF onset and reduced Trpv4 and Klf2 expression in cerebral microvessels, two key vasoprotective genes.

Diastolic dysfunction↗
PubMed1990

MRI in familial multiple sclerosis.

We obtained cranial MRIs of 76 individuals from 13 MS multiplex families. Thirty-one MS patients and 45 normal family members participated in the study. Twenty-eight of the 31 individuals with definite or probable MS had multiple white matter lesions by MRI. Thirty-five normal family members had normal MRIs, and 10 had abnormal studies. Four normal individuals under age 40 had abnormal MRIs. Three had multiple white matter lesions. The 4th had a single small white matter lesion in the left centrum semiovale. Six normal individuals over age 50 had multiple white matter lesions. Although diffuse white matter lesions in individuals over age 50 should be interpreted with caution, these lesions in individuals under age 40 with no history of underlying medical illness are suggestive of demyelination. The results of the present study indicate that subclinical MS may be present in apparently normal members of multiplex families.

Adult↗
PubMed2006

Time-multiplexed three-dimensional displays based on directional backlights with fast-switching liquid-crystal displays.

An autostereoscopic display using a directional backlight with a fast-switching liquid-crystal (LC) display was designed and fabricated to obtain a better perception of 3D images by enhanced resolution and brightness. A grooved light guide in combination with an asymmetric focusing foil was utilized to redirect the emitting cones of light to the left and right eyes, respectively. By designing the groove structures of the focusing foil with rotation from -1.5 degrees to 1.5 degrees in the gradient and having the pitch ratio of the grooved light guide to the focusing foil of less than 3, the boundary angle then shifts from normal viewing and the moiré phenomenon can be suppressed. Cross talk of less than 6% and a LC response time of faster than 7.1 ms further improve the stereoscopic image perception. Additionally, 2D-3D compatibility is provided.

Journal Article↗
PubMed2026

PASTA: versatile tyramide-oligonucleotide amplification for multimodal spatial biology.

Spatial proteomics is limited by detection sensitivity, multiplexing and multimodal integration, leaving a gap between discovery and clinical assays. Here we present protein and nucleic acid serial tyramide amplification (PASTA), using horseradish peroxidase-mediated oligonucleotide deposition and cyclical imaging for high-plex, multimodal spatial profiling. Compatible with conjugated antibodies and in situ hybridization, PASTA enables simultaneous protein and RNA codetection from formalin-fixed, paraffin-embedded samples, providing a cost-effective bridge from discovery to clinical validation.

Tyramine↗
PubMed2003

High-content assays for ligand regulation of G-protein-coupled receptors.

High-content assays rely on the imaging of cellular events. They can be used to monitor the activation of G-protein-coupled receptors (or other receptors), their internalization into the cell, or alterations in their amount. In addition, multiplexed assays can provide further information about the characteristics of the receptor. Recent improvements in throughput using high-content screening platforms means that such assays are now an integral element of functional analysis in the drug discovery process.

Animals↗
PubMed1994

Mononeuritis multiplex. A harbinger of acute leukemia in relapse.

OBJECTIVE: To report the findings in a patient who developed severe mononeuritis multiplex in the setting of hematologic remission from acute myeloid leukemia. DESIGN: Single case report of the patient, hospital course, and autopsy findings. PATIENT: A 63-year-old woman with a history of acute myeloid leukemia in hematologic remission experienced a succession of acute clinical neuropathies (left median, right radial, and left sciatica) several months before hematologic relapse of leukemia. Electrophysiologic tests localized the abnormalities of the left median and right radial nerves to the arms, and a magnetic resonance imaging scan of the right arm revealed focal swelling of the radial nerve proximal to the elbow. The patient refused treatment for leukemic relapse and died about 6 months after the onset of the neuropathies. An autopsy revealed leukemic infiltrates in multiple nerves without appreciable involvement of the cauda equina or many of the proximal nerves. CONCLUSION: Mononeuritis multiplex, without polyradiculopathy or diffuse peripheral neuropathy, can be a presenting feature of leukemia.

Female↗
PubMed1991

Enzymatic multiplex DNA sequencing.

The problem of reading DNA sequence films has been reformulated using an easily implemented, multiplex version of enzymatic DNA sequencing. By utilizing a uniquely tagged primer for each base-specific sequencing reaction, the four reactions can be pooled and electrophoresed in a single lane. This approach has been previously proposed for use with fluorescently labelled probes (1), and is analogous to the principle used in four-dye fluorescence sequencing except that the signals are resolved following electrophoresis (2). After transfer to a nylon membrane, images are obtained separately for each of the four reactions by hybridization using oligonucleotide probes. The images can then be superimposed to reconstitute a complete sequence pattern. In this way the correction of gel distortion effects and accurate band registration are considerably simplified, as each of the four base-specific ladders require very similar corrections. The methods therefore provide the basis for a second generation of more accurate and reliable film reading programs, as well as being useful for conventional multiplex sequencing. Unlike the original multiplex protocol (3), the approach described is suitable for small projects, as multiple cloning vectors are not used. Although more than one vector can be utilized, only a library of fragments cloned into any single phage, phagemid or plasmid vector is actually required, together with a set of tagged oligonucleotide primers.

Base Sequence↗
PubMed2004

Validation and implementation of the PowerPlex 16 BIO System STR multiplex for forensic casework.

The PowerPlex 16 BIO multiplex short tandem repeat (STR) system contains the 13 CODIS loci (FGA, TPOX, D8S1179, vWA, D18S51, D21S11, TH01, D3S1358, CSF1PO, D16S539, D7S820, D13S317, and DS5S818), plus two pentanucleotide repeat loci (Penta D and Penta E) and the sex-identifying locus. Amelogenin. The PowerPlex 16 BIO System is optimized for use with the Hitachi FMBIO gel imaging systems. A consortium of seven independent laboratories collaborated to perform the studies defined by the FBI standards for performing a developmental validation, including the evaluation of sample concordance, percent stutter determination, nonprobative casework, precision, sensitivity, mixture determination, effect of substrates, the impact of environmental insults, and species specificity. All samples tested for concordance were consistent except for one sample from the Virginia Division of Forensic Science database that displayed discordance at D13S317, a locus whose primer sequence was altered. Stutter values were comparable to those of other STR multiplex systems, the precision was comparable to other multiplexes analyzed by gel electrophoresis, the DNA profiles were unchanged by the substrate upon which the blood samples were placed, and the nonprobative casework samples re-typed for the PowerPlex 16 BIO System were consistent with previous typing results. When greater than 0.125 ng of DNA was placed into the PowerPlex 16 BIO System amplification reaction, a full profile was generated by all laboratories. The mixture study results were comparable to those reported for other multiplex systems, the environmental study demonstrated a loss of larger molecular weight loci when samples were incubated at elevated temperatures for a prolonged period of time, and the only notable cross species hybridization was observed with primate DNA samples. This extensive validation work performed demonstrates that the PowerPlex 16 BIO System provides STR data of a quality comparable with other PowerPlex STR multiplex kits as well as other widely used STR multiplexes and is thus suitable for evidentiary casework analysis as well as database sample profiling.

Alleles↗
PubMed2005

Histomathematical analysis of clinical specimens: challenges and progress.

Proteomic analysis of clinical tissue specimens is a difficult undertaking. Described here is a multiplex study of protein expression levels in histological sections of human prostate that addresses many of the associated challenges. Whole-mount sections from 10 prostatectomy specimens were studied using 15 antibodies, immunohistochemical staining, digital imaging, and mathematical analysis of the data sets. The approach was successful in stratifying cell lineages present in the samples based on proteomic patterns, including differentiating normal epithelium from cancer. This strategy likely will be a useful method for extending the number of proteins that can be analyzed in clinical cancer specimens using currently available laboratory techniques.

Epithelial Cells↗
PubMed1996

Imaging localized retinal dysfunction with the multifocal electroretinogram.

Conventional electroretinographic techniques do not permit efficient mapping of retinal responsiveness for the detection of small dysfunctional areas. This study explores the application of a new technique that makes such mapping possible. It utilizes a multifocal electroretinogram technique based on binary m sequences that simultaneously tests a large number of small retinal areas by multiplexing their responses onto a single signal derived from the human cornea. The focal responses are subsequently extracted for the derivation of high-resolution maps that characterize retinal responsiveness. The required recording times are short enough to make such testing feasible in the clinic. In this study we demonstrate the high sensitivity of the technique by mapping a small area that has been partially bleached by a strobe flash in a normal retina and by mapping dysfunctional areas in three patients with different, well-documented retinal pathologies. The results suggest that the multifocal electroretinogram has the potential to become a valuable clinical tool.

Adult↗