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Hui Meng

Publications and source records attributed to Hui Meng.

At least 19 recordsLinked to original sources
PubMed2023

Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the DMD gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retriever muscular dystrophy (GRMD) model, may more readily translate to humans. To evaluate the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)-microdystrophin (μDys5) construct, we performed a blinded, placebo-controlled study in which 12 GRMD dogs were divided among four dose groups [control, 1 × 1013 vector genomes per kilogram (vg/kg), 1 × 1014 vg/kg, and 2 × 1014 vg/kg; n = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-μDys5, and followed for 90 days after dosing. All dogs received prednisone (1 milligram/kilogram) for a total of 5 weeks from day -7 through day 28. We observed dose-dependent increases in tissue vector genome copy numbers; μDys5 protein in multiple appendicular muscles, the diaphragm, and heart; limb and respiratory muscle functional improvement; and reduction of histopathologic lesions. As expected, given that a truncated dystrophin protein was generated, phenotypic test results and histopathologic lesions did not fully normalize. All administrations were well tolerated, and adverse events were not seen. These data suggest that systemically administered AAV-microdystrophin may be dosed safely and could provide therapeutic benefit for patients with DMD.

Animals↗
PubMed2006

Three-dimensional kinematics at the level of the oculomotor plant.

Motor systems often require that superfluous degrees of freedom be constrained. For the oculomotor system, a redundancy in the degrees of freedom occurs during visually guided eye movements and is solved by implementing Listing's law and the half-angle rule, kinematic constraints that limit the range of eye positions and angular velocities used by the eyes. These constraints have been attributed either to neurally generated commands or to the physical mechanics of the eye and its surrounding muscles and tissues (i.e., the ocular plant). To directly test whether the ocular plant implements the half-angle rule, critical to the maintenance of Listing's law, we microstimulated the abducens nerve with the eye at different initial vertical eye positions. We report that the electrically evoked eye velocity exhibits the same eye position dependence as seen in visually guided smooth-pursuit eye movements. These results support an important role for the ocular plant in providing a solution to the degrees-of-freedom problem during eye movements.

Abducens Nerve↗
PubMed2006

Neural correlates of the dependence of compensatory eye movements during translation on target distance and eccentricity.

To stabilize objects of interest on the fovea during translation, vestibular-driven compensatory eye movements [translational vestibulo-ocular reflex (TVOR)] must scale with both target distance and eccentricity. To identify the neural correlates of these properties, we recorded from different groups of eye movement-sensitive neurons in the prepositus hypoglossi and vestibular nuclei of macaque monkeys during lateral and fore-aft displacements. All neuron types exhibited some increase in modulation amplitude as a function of target distance during high-frequency (4 Hz) lateral motion in darkness, with slopes that were correlated with the cell's pursuit gain, but not eye position sensitivity. Vergence angle dependence was largest for burst-tonic (BT) and contralateral eye-head (EH) neurons and smallest for ipsilateral EH and position-vestibular-pause (PVP) cells. On the other hand, the EH and PVP neurons with ipsilateral eye movement preferences exhibited the largest vergence-independent responses, which would be inappropriate to drive the TVOR. In addition to target distance, the TVOR also scales with target eccentricity, as evidenced during fore-aft motion, where eye velocity amplitude exhibits a "V-shaped " dependence and phase shifts 180 degrees for right versus left eye positions. Both the modulation amplitude and phase of BT and contralateral EH cells scaled with eye position, similar to the evoked eye movements during fore-aft motion. In contrast, the response modulation of ipsilateral EH and PVP cells during fore-aft motion was characterized by neither the V-shaped scaling nor the phase reversal. These results show that distinct premotor cell types carry neural signals that are appropriately scaled by vergence angle and eye position to generate the geometrically appropriate compensatory eye movements in the translational vestibulo-ocular reflex.

Accommodation, Ocular↗
PubMed2006

Validation of CFD simulations of cerebral aneurysms with implication of geometric variations.

BACKGROUND: Computational fluid dynamics (CFD) simulations using medical-image-based anatomical vascular geometry are now gaining clinical relevance. This study aimed at validating the CFD methodology for studying cerebral aneurysms by using particle image velocimetry (PIV) measurements, with a focus on the effects of small geometric variations in aneurysm models on the flow dynamics obtained with CFD. METHOD OF APPROACH: An experimental phantom was fabricated out of silicone elastomer to best mimic a spherical aneurysm model. PIV measurements were obtained from the phantom and compared with the CFD results from an ideal spherical aneurysm model (S1). These measurements were also compared with CFD results, based on the geometry reconstructed from three-dimensional images of the experimental phantom. We further performed CFD analysis on two geometric variations, S2 and S3, of the phantom to investigate the effects of small geometric variations on the aneurysmal flow field. Results. We found poor agreement between the CFD results from the ideal spherical aneurysm model and the PIV measurements from the phantom, including inconsistent secondary flow patterns. The CFD results based on the actual phantom geometry, however, matched well with the PIV measurements. CFD of models S2 and S3 produced qualitatively similar flow fields to that of the phantom but quantitatively significant changes in key hemodynamic parameters such as vorticity, positive circulation, and wall shear stress. CONCLUSION: CFD simulation results can closely match experimental measurements as long as both are performed on the same model geometry. Small geometric variations on the aneurysm model can significantly alter the flow-field and key hemodynamic parameters. Since medical images are subjected to geometric uncertainties, image-based patient-specific CFD results must be carefully scrutinized before providing clinical feedback.

Animals↗
PubMed2006

Intracranial aneurysms: links among inflammation, hemodynamics and vascular remodeling.

Abnormal vascular remodeling mediated by inflammatory cells has been identified as a key pathologic component of various vascular diseases, including abdominal aortic aneurysms, brain arteriovenous malformations and atherosclerosis. Based on findings from observational studies that analysed human intracranial aneurysms and experimental studies that utilized animal models, an emerging concept suggests that a key component of the pathophysiology of intracranial aneurysms is sustained abnormal vascular remodeling coupled with inflammation. This concept may provide a new treatment strategy to utilize agents to inhibit inflammation or cytokines produced by inflammatory cells such as matrix metalloproteinases. Such an approach would aim to stabilize these vascular lesions and prevent future expansion or rupture.

Animals↗
PubMed2006

Neuroendoscopic management of symptomatic septum pellucidum cysts.

OBJECTIVE: Ten rare cases of symptomatic septum pellucidum cysts in patients who underwent endoscopic fenestration are described. The approaches and techniques used in the management of these cysts and the endoscopic surgical indications are discussed. CLINICAL PRESENTATION: In the past 5 years, 10 patients (age range, 3-60 yr) with symptomatic septum pellucidum cysts underwent neuroendoscopic fenestration. The most common symptom was intermittent headache (seven patients) accompanied by dizziness, vomiting, and epileptic seizures. Two patients presented with epileptic seizures. One patient presented with abnormally increased head circumference. Magnetic resonance imaging scans of 10 patients showed septum pellucidum cysts, two with hydrocephalus, and two with pituitary microadenoma. INTERVENTION: All 10 patients underwent endoscopic fenestration with a rigid endoscope via a frontal approach. Eight cases were performed freehand. Two cases were assisted by a frameless neuronavigation system. Postoperatively, the mass effect of the cysts and the symptoms resolved immediately, and computed tomographic or magnetic resonance imaging scans showed significant decrease in the cyst size and no recurrence during follow-up. Ventricular sizes in the two patients with hydrocephalus were normal. CONCLUSION: Neuroendoscopic pellucidotomy could be an effective, safe, and convenient therapeutic method for symptomatic septum pellucidum cysts. This approach might provide communication between the cyst and the ventricular system, thus avoiding shunting or craniotomy. We consider that it is appropriate to use the rigid endoscope via the frontal approach. It is helpful to fill the ventricles with lactated Ringer's solution and leave an external drain after surgery.

Adolescent↗
PubMed2006

A model system for mapping vascular responses to complex hemodynamics at arterial bifurcations in vivo.

OBJECTIVE: Cerebral aneurysms are preferentially located at arterial bifurcation apices with complex hemodynamics. To understand disease mechanisms associated with aneurysm initiation, we attempted to establish a causal relationship between local hemodynamics and vascular responses. METHODS: Arterial bifurcations were surgically created from native common carotid arteries in two dogs, angiographically imaged 2 weeks and 2 months later, and then excised. We characterized local morphological changes in response to specifically manipulated hemodynamics. Computational fluid dynamics simulations were performed on the in vivo images and results mapped onto histological images. RESULTS: Local flow conditions, such as high wall shear stress and high wall shear stress gradient, were found to be associated with vascular changes, including an intimal pad in the flow impingement region and a "groove" bearing the characteristics of an early aneurysm. CONCLUSION: This novel method of histohemodynamic micromapping reveals a direct correlation between an altered hemodynamic microenvironment and vascular responses consistent with aneurysm development.

Animals↗
PubMed2005

Four-dimensional dynamic flow measurement by holographic particle image velocimetry.

The ultimate goal of holographic particle image velocimetry (HPIV) is to provide space- and time-resolved measurement of complex flows. Recent new understanding of holographic imaging of small particles, pertaining to intrinsic aberration and noise in particular, has enabled us to elucidate fundamental issues in HPIV and implement a new HPIV system. This system is based on our previously reported off-axis HPIV setup, but the design is optimized by incorporating our new insights of holographic particle imaging characteristics. Furthermore, the new system benefits from advanced data processing algorithms and distributed parallel computing technology. Because of its robustness and efficiency, for the first time to our knowledge, the goal of both temporally and spatially resolved flow measurements becomes tangible. We demonstrate its temporal measurement capability by a series of phase-locked dynamic measurements of instantaneous three-dimensional, three-component velocity fields in a highly three-dimensional vortical flow-the flow past a tab.

Journal Article↗
PubMed2005

Tungsten carbide nanocrystal promoted Pt/C electrocatalysts for oxygen reduction.

Tungsten carbide nanocrystals on carbon (W2C/C) and tungsten carbide nanocrystals and Pt on carbon (Pt-W2C/C) composite electrocatalysts were prepared by the intermittent microwave heating (IMH) method and tested for the electroreduction of oxygen in the acidic media for the first time. The results revealed that the tungsten carbide nanocrystal promoted Pt/C electrocatalyst was very active for ORR with the onset potential of 1.0 V vs SHE at ambient temperature that is over 100 mV more positive compared with that of traditional Pt/C electrocatalyst. The kinetic parameters were determined. The exchange current densities at both high and low overpotential regions are two orders higher for ORR on Pt-W2C/C than that on Pt/C, showing a synergetic effect to improve the activity for ORR. The novel electrocatalysts show a poisoning resistant property toward methanol.

Journal Article↗
PubMed2005

Contrast settling in cerebral aneurysm angiography.

During angiography, blood flow is visualized with a radiopaque contrast agent, which is denser than blood. In complex vasculature, such as cerebral saccular aneurysms, the density difference may produce an appreciable gravity effect, where the contrast material separates from blood and settles along the gravity direction. Although contrast settling has been occasionally reported before, the fluid mechanics behind it have not been explored. Furthermore, the severity of contrast settling in cerebral aneurysms varies significantly from case to case. Therefore, a better understanding of the physical principles behind this phenomenon is needed to evaluate contrast settling in clinical angiography. In this study, flow in two identical groups of sidewall aneurysm models with varying parent-vessel curvature was examined by angiography. Intravascular stents were deployed into one group of the models. To detect contrast settling, we used lateral view angiography. Time-intensity curves were analysed from the angiographic data, and a computational fluid dynamic analysis was conducted. Results showed that contrast settling was strongly related to the local flow dynamics. We used the Froude number, a ratio of flow inertia to gravity force, to characterize the significance of gravity force. An aneurysm with a larger vessel curvature experienced higher flow, which resulted in a larger Froude number and, thus, less gravitational settling. Addition of a stent reduced the aneurysmal flow, thereby increasing the contrast settling. We found that contrast settling resulted in an elevated washout tail in the time-intensity curve. However, this signature is not unique to contrast settling. To determine whether contrast settling is present, a lateral view should be obtained in addition to the anteroposterior (AP) view routinely used clinically so as to rule out contrast settling and hence to enable a valid time-intensity curve analysis of blood flow in the aneurysm.

Algorithms↗
PubMed2005

Pursuit--vestibular interactions in brain stem neurons during rotation and translation.

Under natural conditions, the vestibular and pursuit systems work synergistically to stabilize the visual scene during movement. How translational vestibular signals [translational vestibuloocular reflex (TVOR)] are processed in the premotor pathways for slow eye movements continues to remain a challenging question. To further our understanding of how premotor neurons contribute to this processing, we recorded neural activities from the prepositus and rostral medial vestibular nuclei in macaque monkeys. Vestibular neurons were tested during 0.5-Hz rotation and lateral translation (both with gaze stable and during VOR cancellation tasks), as well as during smooth pursuit eye movements. Data were collected at two different viewing distances, 80 and 20 cm. Based on their responses to rotation and pursuit, eye-movement-sensitive neurons were classified into position-vestibular-pause (PVP) neurons, eye-head (EH) neurons, and burst-tonic (BT) cells. We found that approximately half of the type II PVP and EH neurons with ipsilateral eye movement preference were modulated during TVOR cancellation. In contrast, few of the EH and none of the type I PVP cells with contralateral eye movement preference modulated during translation in the absence of eye movements; nor did any of the BT neurons change their firing rates during TVOR cancellation. Of the type II PVP and EH neurons that modulated during TVOR cancellation, cell firing rates increased for either ipsilateral or contralateral displacement, a property that could not be predicted on the basis of their rotational or pursuit responses. In contrast, under stable gaze conditions, all neuron types, including EH cells, were modulated during translation according to their ipsilateral/contralateral preference for pursuit eye movements. Differences in translational response sensitivities for far versus near targets were seen only in type II PVP and EH cells. There was no effect of viewing distance on response phase for any cell type. When expressed relative to motor output, neural sensitivities during translation (although not during rotation) and pursuit were equivalent, particularly for the 20-cm viewing distance. These results suggest that neural activities during the TVOR were more motorlike compared with cell responses during the rotational vestibuloocular reflex (RVOR). We also found that neural responses under stable gaze conditions could not always be predicted by a linear vectorial addition of the cell activities during pursuit and VOR cancellation. The departure from linearity was more pronounced for the TVOR under near-viewing conditions. These results extend previous observations for the neural processing of otolith signals within the premotor circuitry that generates the RVOR and smooth pursuit eye movements.

Action Potentials↗
PubMed2005

Mathematical model of the rupture mechanism of intracranial saccular aneurysms through daughter aneurysm formation and growth.

OBJECTIVES: Daughter aneurysms have been strongly associated with saccular aneurysm rupture. We constructed a mathematical model to help explain this association as a possible hemodynamic mechanism for intracranial saccular aneurysm rupture. METHODS: Our model is based on the assumption that when an aneurysm reaches a state of imminent rupture, the weakest area of the aneurysm wall responds passively to a surge of intra-aneurysmal pressure by forming a daughter aneurysm that will be the site of the eventual rupture. The daughter and parent aneurysms were assumed to be spherical. Using mathematical modeling, the growth of the daughter aneurysm was observed. To obtain the change in tensile stress in the daughter aneurysm wall under constant pressure and changing geometry, the Law of Laplace was applied to the parent and the daughter aneurysms. RESULTS: The model reveals that the stress factor, i.e. tensile stress in the daughter aneurysm wall relative to the wall strength (rupture point), is dependent on two geometric parameters: the orifice factor (mu), which represents the relative size of the daughter aneurysm orifice radius to the parent aneurysm radius; and the aspect ratio (lambda), which represents the height-to-orifice ratio of the daughter aneurysm. As the daughter aneurysm develops, the stress factor first decreases to protect against rupture. Minimal stress is attained at an aspect ratio (lambda) of 0.577 regardless of the orifice factor. This is a relatively stable state. Further growth of the daughter aneurysm results in an increase of stress above the minimum, eventually leading to rupture at a stress factor of 1. A smaller orifice factor mu allows this aneurysm to grow to a higher aspect ratio lambda before rupture. DISCUSSION: Daughter aneurysm formation is a likely path to aneurysm rupture. The formation of a daughter aneurysm temporarily decreases the tensile stress within a parent aneurysm in which rupture is imminent, indicating a temporary protective role of daughter aneurysm development. Aneurysms harboring daughter aneurysms are at a more advanced stage of development, hence at a greater risk for rupture. The severity of the rupture risk can be estimated on the basis of daughter aneurysm geometry; aspect ratio lambda > 0.577 indicates a greater risk of rupture. Furthermore, daughter aneurysms with larger orifices are associated with a greater risk of rupture.

Aneurysm, Ruptured↗
PubMed2005

[Research on the mechanisms of PTEN gene inactivation in ovarian cancer].

OBJECTIVE: To investigate the mechanisms of PTEN gene inactivation starting from DNA, mRNA and protein levels in ovarian cancers. METHODS: Tumor tissue samples were obtained from 48 patients with epithelial ovarian cancers. Using four polymorphic markers (D10s541, D10s583, D10s1687 and D10s2491) within and flanking the PTEN gene located in chromosome 10q 23.3, polymerase chain reaction (PCR) and loss of heterozygosity (LOH) were introduced to examine LOH of PTEN gene; PCR-single strand conformation polymorphism (PCR-SSCP) was introduced to examine mutations of the fifth, sixth, seventh, and eighth exons of PTEN. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (SP method) were applied to detect PTEN mRNA and PTEN protein expressions, respectively. RESULTS: LOH of PTEN gene was observed in 19 of 48 (39.6%) ovarian cancers. PTEN mutations were found only in 2 (4.2%) of the cases. Absence of PTEN mRNA expression was 18.8% (9 of 48). Immunostaining of 48 cancer samples revealed that 13 (27.1%) were PTEN immunostain negative. Of these 13 samples, only 2 (15.4%) had structural, biallelic inactivation by intragenic PTEN mutations and loss of the remaining wild-type allele; 7 (53.8%) showed evidence of LOH, 5 of these 7 samples showed deletion of PTEN mRNA expression, another 2 samples showed positive expression of PTEN mRNA; 4 (30.8%) tumors had neither PTEN gene mutation nor LOH but exhibited no PTEN protein expression, 2 of these 4 cases showed deletion of PTEN mRNA expression, another 2 showed positive expression of PTEN mRNA. For the cases of PTEN protein absent staining, the rate of LOH was 69.2% (9 of 13), higher than 28.6% (10 of 35) for the positive staining (P < 0.05). CONCLUSIONS: PTEN gene inactivation may contribute to epithelial ovarian carcinogenesis. There may be several mechanisms of PTEN gene inactivation in ovarian cancers. Protein expression deletions may be a significant mechanism.

Adult↗
PubMed2004

Multiple reference frames for motion in the primate cerebellum.

Knowledge of body motion through space is necessary for spatial orientation, self-motion perception, and postural control. Yet, sensory afferent signals may not directly provide such information to the brain. Because motion detected by the vestibular end organs is encoded in a head-fixed frame of reference, a coordinate transformation is thus required to encode body motion. In this study, we investigated whether cerebellar motion-sensitive neurons encode the translation of the body through space. We systematically changed both the direction of motion relative to the body and the static orientation of the head relative to the trunk. The activities of motion-sensitive neurons in the most medial of the deep cerebellar nuclei, the rostral fastigial nucleus, were compared with those in the brainstem vestibular nuclei. We found a distributed representation of reference frames for motion in the rostral fastigial nucleus, in contrast to cells in the vestibular nuclei, which primarily encoded motion in a head-fixed reference frame. This differential representation of motion-related information implies potential differences in the functional roles of these areas.

Acceleration↗
PubMed2004

Eye movements evoked by selective saccular nerve stimulation in cats.

OBJECTIVE: Because of technical obstacles in controlling current spread to adjacent peripheral nerve, eye movements evoked by activation of the otolith organs have not been investigated in detail compared to eye movements evoked by activation of the canal organs. We attempted to solve this problem by applying more sensitive methods using fine needle and strictly controlling stimulus current intensity compare with filed potential for selective stimulation. METHODS: Eye movements evoked by selective, unilateral saccular (SAC) nerve stimulation were investigated using both electrooculography (EOG) and video recording in decerebrated cats in the presence or absence of anesthesia. Electrical stimulation was applied to the SAC nerve through implanted acupuncture needles. RESULTS: In the absence of anesthesia and with stimulus intensities less than (3.1 +/- 2.7) x N(1)T, we found supraduction in both eyes or in either the ipsilateral or contralateral eye of different cats. We observed downward eye movements using a stronger stimulus intensity ((6.2 +/- 2.9)) x N(1)T). The threshold for downward eye movements was significantly greater than that for upward eye movements (P < 0.05). In anesthetized cats, only downward eye movements were observed when stimulus intensities less than 10 x N(1)T ((7.8 +/- 2.3) x N(1)T) were used. CONCLUSION: These results confirm the known sacculo-ocular anatomical connections, which are involved predominantly in vertical eye movements. Because the sacculo-ocular connections are relatively weak, the normal supraduction evoked by SAC activation can be easily modified by factors such as level of anesthesia and the method of stimulation.

Animals↗
PubMed2004

Measurement of flow modification in phantom aneurysm model: comparison of coils and a longitudinally and axially asymmetric stent--initial findings.

Dye-dilution imaging sequences were performed and time-density curves were constructed in elastomer vessel aneurysm models to demonstrate the effectiveness of coils and an asymmetric stent in disrupting standard vortex flow. Compared with the use of coils, the use of stents led to marked flow modification, as seen with imaging sequences, and substantially slower inflow, as indicated by time-density curves, owing to the low-porosity region of the stent that covers the aneurysm orifice. These flow examination results indicate that potentially favorable flow modification features can be created by using the described asymmetric stent design, the use of which may lead to alternative methods of image-guided endovascular cerebral aneurysm therapy.

Blood Vessel Prosthesis Implantation↗
PubMed2004

Intrinsic speckle noise in off-axis particle holography.

In holographic imaging of particle fields, the interference among coherent wave fronts associated with particle scattering gives rise to intrinsic speckle noise, which sets a fundamental limit on the amount of information that particle holography can deliver. It has been established that the intrinsic speckle noise is especially severe in in-line holography because of superposition of virtual image waves, the direct transmitted wave, and the real image. However, at sufficiently high particle number densities, such as those typical in holographic particle image velocimetry (HPIV) applications, intrinsic speckle noise also arises in off-axis particle holography from self-interference among wave fronts that form the real image of particles. To overcome the latter problem we have constructed a mathematical model that relates the first- and second-order statistical properties of the intrinsic speckle noise to relevant holographic system parameters. Consistent with our experimental data, the model provides a direct estimate of the information capacity of particle holography. We show that the noise-limited information capacity can be expressed as the product of particle number density and the extent of the particle field along the optical axis. A large angular aperture of the hologram contributes directly to achievement of high information capacity. We also show that filtering in either digital or optical form is generally ineffective in removing the intrinsic speckle noise from the particle image as a result of the similar spectral properties of the two. These findings emphasize the importance of angular aperture in designing holographic particle imaging systems.

Journal Article↗