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Biomedical subjects

G Wang

Publications and source records attributed to G Wang.

At least 253 records · Page 14Linked to original sources

Hyperactive tendon reflexes in spastic multiple sclerosis: measures and mechanisms of action.

OBJECTIVE: To develop new measures of tendon reflexes and evaluate hyperactive reflexes in patients with spastic multiple sclerosis (MS). DESIGN: With the subject relaxed, a hand-held instrumented hammer was used to tap the patellar tendon and record the tapping force, while knee extension torque and quadriceps EMG were recorded isometrically as measures of the reflex response. SETTING: Research laboratory in a rehabilitation hospital. SUBJECTS: Ten spastic MS and 14 healthy subjects. MAIN OUTCOME MEASURES: Tendon tapping force (designated as system input), reflex torque (as output), their dynamic relationship (characterized as system parameters tendon reflex gain, contraction rate, and reflex loop delay), Ashworth scale, and tendon reflex scale. RESULTS: The system parameters provide more repeatable measures than do input or output parameters alone because they quantify the input and output simultaneously and dynamically. Compared with control subjects, MS patients had a significantly lower threshold in tapping force (p = .026), yet their evoked reflex torque was significantly higher (p = .033). Despite significant quadriceps weakness (p < .0001), MS patients had a significantly higher reflex gain (p = .0002) and contraction rate (p = .0002), and shorter reflex loop delay (p = .0046), indicating hyperexcitability of motoneurons and peripheral receptors, and indicating that relatively more of the muscle was activated reflexively, with greater recruitment of larger fast-twitch fibers. Both the reflex gain and rate measures correlated more closely with the Ashworth scale and tendon reflex scale than did the output measures, indicating their potential clinical value. CONCLUSIONS: With appropriate simplification, the method may be used in clinical practice to quantify more precisely the tendon jerk than is currently feasible with standard clinical tests.

Adult↗

Conformationally locked nucleosides. Synthesis of oligodeoxynucleotides containing 3'-amino-3'-deoxy-3'-N,5'(R)-C-ethylenethymidine.

3'-Amino-3'-deoxy-5'-O-(4,4'-dimethoxytrityl)-3'-N,5'(R)-C-ethylenethymidine (6) was synthesized starting from 3'-azido-3'-deoxythymidine. Condensation of 6 with 5'O-(H-phosphonyl)thymidine and 5'-O-(p-nitrophenoxycarbonyl)thymidine derivatives gave dinucleotide and dinucleoside derivatives, respectively, which were incorporated into oligodeoxynucleotides (ODNs). Tm data of the modified ODNs are also presented.

DNA↗

Damage and repair of DNA in HIV encephalitis.

Neuronal damage and dementia are common sequelae of HIV encephalitis. The mechanism by which HIV infection of CNS macrophages results in neuronal damage is not known. We examined the brains from 15 AIDS autopsies (8 with HIV encephalitis and 7 without) and 4 non-infected control autopsies for the presence of DNA strand breaks, for associated changes in the expression of the DNA repair enzymes KU80 and Poly (ADP-ribose) polymerase (PARP), and for accumulation of amyloid precursor protein (APP). Abundant DNA damage was observed with terminal transferase-mediated dUTP nick end-labeling (TUNEL), however, there was no morphologic evidence of significant neuroglial apoptosis. The DNA repair enzyme KU80 was immunocytochemically detectable in neuronal and glial cells in autopsy brains from patients with and without HIV encephalitis; however, in cases with HIV encephalitis the staining was more prominent than in the infected or non-infected controls without encephalitis. There was no difference in KU80 immunostaining in oligodendroglia from autopsies with and without encephalitis. Immunostaining for PARP was more intense in gray and white matter of cases with HIV encephalitis. No clear spatial relationship existed between expression of DNA repair enzymes and the spatial proximity of microglial nodules or HIV-infected macrophages. The cytoplasm of cortical and subcortical neurons immunostained for APP Stronger cortical neuronal APP staining was observed in cases without HIV encephalitis. Staining of deep gray matter neurons was similar, irrespective of the presence or absence of encephalitis. While foci of intense APP staining were noted in white matter not related to HIV infection, they were associated with foci of opportunistic infections (e.g. due to CMV or PML). We conclude that damaged DNA and altered patterns of expression of DNA repair proteins and APP are common findings in the brains of AIDS patients at autopsy, but do not have a spatial relationship to HIV-infected macrophages.

AIDS Dementia Complex↗

Digital X-ray stereophotogrammetry for cochlear implantation.

Multielectrode, intracochlear implant systems are effective treatment for profound sensorineural hearing loss. In some cases, these systems do not perform well, which may be partially due to variations in implant location within the cochlea. Determination of each electrode's position in a patient's inner ear provides an in vivo basis for both the cochlear modeling of electrical fields and the future design of electrode arrays that deliver electrical stimulation to surviving auditory neurons, and may improve speech processor programming for better speech recognition. We developed an X-ray stereophotogrammetric approach to localize implanted electrodes in three dimensions. Stereophotogrammetry of implanted electrodes is formulated in weak perspective geometry, with knowledge of a three-dimensional (3-D) reference structure and electrode positions in each of two digital stereo-images. The localization error is theoretically, numerically, and experimentally quantified. Both numerical and experimental results demonstrate the feasibility of the technique.

Biomedical Engineering↗

Three-dimensional geometric modeling of the cochlea using helico-spiral approximation.

In this paper, the three-dimensional geometry of the human cochlea is modeled by the helico-spiral seashell model. The 3-D helico-spiral model, the generalized representation of the Archimedian spiral model, provides a framework for measuring cochlear features based on consistent estimation of model parameters. Nonlinear least square minimization based algorithms are developed for the identification of rotation, center and intrinsic parameters of the helico-spiral representation. Two algorithms are designed for the rotation axis aligned to the modiolar axis: one is more susceptible in the presence of noise, while the other allows applicability to two-dimensional data sets. The estimated center and intrinsic parameters allow the calculation of length, height and angular positions needed for frequency mapping of multichannel cochlear implant electrodes. Model performance is evaluated with numerically synthesized curves with different levels of added random noise, histologic data and real human cochlear spiral computed tomography data.

Algorithms↗

Feldkamp-type cone-beam tomography in the wavelet framework.

X-ray computed tomography (CT) is in transition from fan-beam to cone-beam geometry. For cone-beam volumetric imaging, reduction of radiation exposure remains an important issue. Because the wavelet approach was shown to be effective and flexible for two-dimensional (2-D) local region reconstruction, we are motivated to perform wavelet local CT in cone-beam geometry. In this paper, we formulate the Feldkamp cone-beam reconstruction from the wavelet perspective, derive both full-scan and half-scan Feldkamp-type formulas for either global or local reconstruction, and demonstrate the feasibility and utility in synthetic and real data. It is found that using the wavelet Feldkamp approach, a three-dimensional (3-D) region of interest (ROI) can be reconstructed with neither severe image artifacts nor any significant constant bias in our simulation and experiments.

Animals↗

X-ray CT metal artifact reduction using wavelets: an application for imaging total hip prostheses.

Traditional computed tomography (CT) reconstructions of total joint prostheses are limited by metal artifacts from corrupted projection data. Published metal artifact reduction methods are based on the assumption that severe attenuation of X-rays by prostheses renders corresponding portions of projection data unavailable, hence the "missing" data are either avoided (in iterative reconstruction) or interpolated (in filtered backprojection with data completion; typically, with filling data "gaps" via linear functions). In this paper, we propose a wavelet-based multiresolution analysis method for metal artifact reduction, in which information is extracted from corrupted projection data. The wavelet method improves image quality by a successive interpolation in the wavelet domain. Theoretical analysis and experimental results demonstrate that the metal artifacts due to both photon starving and beam hardening can be effectively suppressed using our method. As compared to the filtered backprojection after linear interpolation, the wavelet-based reconstruction is significantly more accurate for depiction of anatomical structures, especially in the immediate neighborhood of the prostheses. This superior imaging precision is highly advantageous in geometric modeling for fitting hip prostheses.

Artifacts↗

Three-dimensional modeling and visualization of the cochlea on the Internet.

Three-dimensional (3-D) modeling and visualization of the cochlea using the World Wide Web (WWW) is an effective way of sharing anatomic information for cochlear implantation over the Internet, particularly for morphometry-based research and resident training in otolaryngology and neuroradiology. In this paper, 3-D modeling, visualization, and animation techniques are integrated in an interactive and platform-independent manner and implemented over the WWW. Cohen's template shape with mean cross-sectional areas of the human cochlea is extended into a 3-D geometrical model. Also, spiral computer tomography data of a patient's cochlea is digitally segmented and geometrically represented. The cochlear electrode array is synthesized according to its specification. Then, cochlear implantation is animated with both idealized and real cochlear models. Insertion length, angular position, and characteristic frequency of individual electrodes are estimated online during the virtual insertion. The optimization of the processing parameters is done to demonstrate the feasibility of this technology for clinical applications.

Cochlea↗

Excitatory versus inhibitory modulation by ATP of neurohypophysial terminal activity in the rat.

Much is now known about the electrophysiological properties of the magnocellular neurones of the hypothalamus. Oxytocin neurones are characterized by an intermittent high frequency discharge during suckling that leads to the pulsatile release of oxytocin into the blood and to subsequent milk ejection. Vasopressin neurones are characterized by their asynchronous phasic activity (bursting) during maintained vasopressin release and the subsequent regulation of water balance. In both cases, it is the clustering of spikes, albeit with different time courses for each peptide, that facilitates hormone release. The mechanism underlying this differential facilitation is one of the major unanswered questions in neuroendocrinology. This paper considers recent evidence that indicates that ATP, co-secreted with vasopressin and oxytocin, may play a key role in the regulation of stimulus-secretion coupling in the neurohypophysis. The activity of the type (II) Ca2+-activated K+ (K(Ca)) channel found in the nerve terminals was significantly increased in the presence of ATP on the cytoplasmic side of the channel. Extracellular ATP, in contrast, inhibited the type II K(Ca) current in a dose-dependent manner. Thus, intracellular and extracellular ATP exert opposite effects on the type II K(Ca) channel of neurohypophysial terminals. Furthermore, ATP opens P2X2 channels to increase intracellular [Ca2+] in the nerve terminals and subsequent arginine vasopressin (AVP) release. In contrast, adenosine, acting via A1 receptors, specifically inhibits only the N-type Ca2+ channel, thus decreasing neuropeptide release. These multiple, conflicting effects of ATP and its metabolite adenosine could explain the patterns of AVP release observed during physiological stimulation in vivo.

Adenosine Triphosphate↗

Design of a dual CCD configuration to improve the signal-to-noise ratio.

The noise of a digital charge coupled device (CCD) detector increases with the readout speed, causing problems in a number of important applications, such as x-ray fluoroscopy and micro-CT. In this paper, we present an approach for the design of a dual-CCD configuration to improve the average signal-to-noise ratio, and hence provide an inexpensive solution within the constraint of the current technology.

Equipment Design↗

Localization of cochlear implant electrodes in radiographs.

Multielectrode cochlear implantation is the most effective treatment for profound sensorineural hearing loss. In vivo three-dimensional 3-D localization of cochlear implant electrodes is important for modeling of the electrical field in the cochlea, design of electrode arrays, and may improve speech processor programming for better speech recognition. The prerequisite for 3-D localization of the electrodes is their 2-D localization in x-ray radiographs. In this paper, we develop a practical method to localize the electrodes with high efficiency, accuracy, and reproducibility. In this method, a priori knowledge of the electrodes and their approximate positions are utilized, an intelligent thresholding and segmentation mechanism is embedded, and the electrode center is computed as the weighted geometric center of segmented electrode pixels. Experiments with physical phantoms and human data demonstrate the feasibility and utility of this method. The PC-based program developed for this project is disseminated on the Web.

Cochlear Implants↗

A localization algorithm and error analysis for stereo x-ray image guidance.

Stereo x-ray radiography attracts increasing attention in major clinical applications. The purpose of this paper is to analyze the 3D localization error for breast biopsy procedures and provide guidelines for improving its accuracy. Our prototype is a CCD based digital stereo x-ray imaging system. The mathematical model consists of two x-ray sources and one stationary detector plane. A closed form least-squares solution is derived for 3D localization of feature points, particularly a biopsy needle tip, from a pair of 2D digital radiographs. Based on the least-squares formula and its first order approximation, the 3D localization error is analyzed in terms of object location, measurement error, separation between the two x-ray sources, and distance from the source to the detector. The stereo imaging and error estimation formulas are numerically simulated and experimentally validated. The data are in agreement with theoretical prediction. These results can be used for the purpose of system design and protocol optimization.

Algorithms↗

Multiplex PCR for detection of genes for Staphylococcus aureus enterotoxins, exfoliative toxins, toxic shock syndrome toxin 1, and methicillin resistance.

A multiplex PCR assay for detection of genes for staphylococcal enterotoxins A to E (entA, entB, entC, entD, and entE), toxic shock syndrome toxin 1 (tst), exfoliative toxins A and B (etaA and etaB), and intrinsic methicillin resistance (mecA) was developed. Detection of femA was used as an internal positive control. The multiplex PCR assay combined the primers for sea to see and femA in one set and those for eta, etb, tst, mecA, and femA in the other set. Validation of the assay was performed using 176 human isolates of Staphylococcus aureus. This assay offers a very specific, quick, reliable, and inexpensive alternative to conventional PCR assays used in clinical laboratories to identify various staphylococcal toxin genes.

Bacterial Toxins↗

Human coronavirus 229E infects polarized airway epithelia from the apical surface.

Gene transfer to differentiated airway epithelia with existing viral vectors is very inefficient when they are applied to the apical surface. This largely reflects the polarized distribution of receptors on the basolateral surface. To identify new receptor-ligand interactions that might be used to redirect vectors to the apical surface, we investigated the process of infection of airway epithelial cells by human coronavirus 229E (HCoV-229E), a common cause of respiratory tract infections. Using immunohistochemistry, we found the receptor for HCoV-229E (CD13 or aminopeptidase N) localized mainly to the apical surface of airway epithelia. When HCoV-229E was applied to the apical or basolateral surface of well-differentiated primary cultures of human airway epithelia, infection primarily occurred from the apical side. Similar results were noted when the virus was applied to cultured human tracheal explants. Newly synthesized virions were released mainly to the apical side. Thus, HCoV-229E preferentially infects human airway epithelia from the apical surface. The spike glycoprotein that mediates HCoV-229E binding and fusion to CD13 is a candidate for pseudotyping retroviral envelopes or modifying other viral vectors.

Cell Line↗

Conservation of heterochromatin protein 1 function.

Heterochromatin represents a cytologically visible state of heritable gene repression. In the yeast, Schizosaccharomyces pombe, the swi6 gene encodes a heterochromatin protein 1 (HP1)-like chromodomain protein that localizes to heterochromatin domains, including the centromeres, telomeres, and the donor mating-type loci, and is involved in silencing at these loci. We identify here the functional domains of swi6p and demonstrate that the chromodomain from a mammalian HP1-like protein, M31, can functionally replace that of swi6p, showing that chromodomain function is conserved from yeasts to humans. Site-directed mutagenesis, based on a modeled three-dimensional structure of the swi6p chromodomain, shows that the hydrophobic amino acids which lie in the core of the structure are critical for biological function. Gel filtration, gel overlay experiments, and mass spectroscopy show that HP1 proteins can self-associate, and we suggest that it is as oligomers that HP1 proteins are incorporated into heterochromatin complexes that silence gene activity.

Amino Acid Sequence↗

Characterization and overproduction of the Escherichia coli appA encoded bifunctional enzyme that exhibits both phytase and acid phosphatase activities.

The appA gene that was previously shown to code for an acid phosphatase instead codes for a bifunctional enzyme exhibiting both acid phosphatase and phytase activities. The purified enzyme with a molecular mass of 44,708 Da was further separated by chromatofocusing into two isoforms of identical size with isoelectric points of 6.5 and 6.3. The isoforms had identical pH optima of 4.5 and were stable at pH values from 2 to 10. The temperature optimum for both phytase isoforms was 60 degrees C. When heated at different pH values the enzyme showed the greatest thermal resistance at pH 3. The pH 6.5 isoform exhibited K(m) and Vmax values of 0.79 mM and 3165 U.mg-1 of protein for phytase activity and 5.5 mM and 712 U.mg-1 of protein for acid phosphatase, respectively. The pH 6.3 isoform exhibited slightly lower K(m) and Vmax values. The enzyme exhibited similar properties to the phytase purified by Greiner et al. (1993), except the specific activity of the enzyme was at least 3.5-fold less than that previously reported, and the N-terminal amino acid sequence was different. The Bradford assay, which was used by Greiner et al. (1993) for determination of enzyme concentration was, in our hands, underestimating protein concentration by a factor of 14. Phytase production using the T7 polymerase expression system was enhanced by selection of a mutant able to grow in a chemically defined medium with lactose as the carbon source and inducer. Using this strain in fed-batch fermentation, phytase production was increased to over 600 U.mL-1. The properties of the phytase including the low pH optimum, protease resistance, and high activity, demonstrates that the enzyme is a good candidate for industrial production as a feed enzyme.

6-Phytase↗

Optimal section spacing in single-detector helical CT.

To define the section spacing that maximizes longitudinal resolution without needless section overlap, the optimal percentage of overlap was computed theoretically and expressed as a constant relative to the effective section thickness. For imaging applications that require maximal longitudinal resolution, single-detector helical computed tomographic images should be reconstructed with at least 60% overlap relative to the effective section thickness.

Algorithms↗