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Biomedical subjects

H Leong

Publications and source records attributed to H Leong.

11 recordsLinked to original sources

Conformational modulation of human cytochrome P450 2E1 by ethanol and other substrates: a CO flash photolysis study.

The alcohol-inducible cytochrome P450 2E1 is a major human hepatic P450 which metabolizes a broad array of endogenous and exogenous compounds, including ethanol, low-molecular weight toxins, and fatty acids. Several substrates are known to stabilize this P450 and inhibit its cellular degradation. Furthermore, ethanol is a known modulator of P450 2E1 substrate metabolism. We examined the CO binding kinetics of P450 2E1 after laser flash photolysis of the heme-CO bond, to probe the effects of ethanol and other substrates on protein conformation and dynamics. Ethanol had an effect on the two kinetic parameters that describe CO binding: it decreased the rate of CO binding, suggesting a decrease in the protein's conformational flexibility, and increased the photosensitivity, which indicates a local effect in the active site region such as strengthening of the heme-CO bond. Other substrates decreased the CO binding rate to varying degrees. Of particular interest is the effect of arachidonic acid, which abolished photodissociation in the absence of ethanol but had no effect in the presence of ethanol. These results are consistent with a model of P450 2E1 whereby arachidonic acid binds along a long hydrophobic binding pocket and blocks exit of CO from the heme region.

Arachidonic Acid↗

Electroencephalographic imaging of higher brain function.

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

Brain↗

Deblurring.

In most instances, traditional EEG methodology provides insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. This article describes a method called Deblurring for increasing the spatial detail of the EEG and for fusing neurophysiologic and neuroanatomic data. Deblurring estimates potentials near the outer convexity of the cortex using a realistic finite element model of the structure of a subject's head determined from their magnetic resonance images. Deblurring is not a source localization technique and thus makes no assumptions about the number or type of generator sources. The validity of Deblurring has been initially tested by comparing deblurred data with potentials measured with subdural grid recordings. Results suggest that deblurred topographic maps, registered with a subject's magnetic resonance imaging and rendered in three dimensions, provide better spatial detail than has heretofore been obtained with scalp EEG recordings. Example results are presented from research studies of somatosensory stimulation, movement, language, attention and working memory. Deblurred ictal EEG data are also presented, indicating that this technique may have future clinical application as an aid to seizure localization and surgical planning.

Brain↗

Sutureless cartilage graft laryngotracheal reconstruction using fibrin sealant.

OBJECTIVE: To determine whether fibrin sealant can replace suture as a means of holding a cartilage graft securely in the trachea. DESIGN: Randomized blinded control study comparing the use of fibrin sealant vs sutures in laryngotracheal reconstruction in ferrets. We compared results at 7 and 30 days. SUBJECTS: Forty ferrets randomized into 2 groups of 20: fibrin sealant and sutures. Within each group, half were studied at 7 days and the rest at 30 days. No ferrets were withdrawn from study because of adverse effects of the intervention. INTERVENTION: A carved costal cartilage graft was placed in the anterior cricoid split incision, and was secured with either fibrin sealant or sutures. All animals were extubated after recovery from anesthesia. Specimens were examined grossly and histologically. RESULTS: All animals survived until humanely killed. The pathologist, unaware of the groupings, measured lumen expansion in millimeters, cartilage graft migration, mucosal in-growth, degree of inflammation, graft integration, and graft viability. The fibrin sealant group had statistically significant (P<.05) better results in mucosal in-growth. In no categories was the suture group better than the fibrin sealant group. In comparing 7-day with 30-day results, the 30-day group had significantly better results in inflammation and graft viability. CONCLUSIONS: Fibrin sealant can be used in place of sutures with improvement in mucosal growth in costal cartilage laryngotracheal reconstruction in the experimental animal model. Use of fibrin sealant (instead of sutures) may result in less surgical trauma and edema, less surgical time, and faster recovery.

Animals↗

Monitoring working memory load during computer-based tasks with EEG pattern recognition methods.

We assessed working memory load during computer use with neural network pattern recognition applied to EEG spectral features. Eight participants performed high-, moderate-, and low-load working memory tasks. Frontal theta EEG activity increased and alpha activity decreased with increasing load. These changes probably reflect task difficulty-related increases in mental effort and the proportion of cortical resources allocated to task performance. In network analyses, test data segments from high and low load levels were discriminated with better than 95% accuracy. More than 80% of test data segments associated with a moderate load could be discriminated from high- or low-load data segments. Statistically significant classification was also achieved when applying networks trained with data from one day to data from another day, when applying networks trained with data from one task to data from another task, and when applying networks trained with data from a group of participants to data from new participants. These results support the feasibility of using EEG-based methods for monitoring cognitive load during human-computer interaction.

Adult↗

Implications of electrolyte dispersion for high resolution EEG methods.

The effective recording area of an EEG electrode is its electrical contact area with the scalp. With techniques that employ wet electrolyte, this area is primarily determined by the extent of electrolyte dispersion rather than by the size of the electrode. The effective recording areas of 10 widely distributed EEG electrodes embedded in an elasticized stretch hat were measured on 7 subjects using a digital multimeter. On average, conventionally prepared electrodes were associated with an electrolyte (standard gel) spread of approximately 1 cm in each of four directions (above, below, right and left of the electrode's center). This implies that EEG electrodes prepared with wet electrolyte should not be spaced less than 2 cm apart unless special precautions are taken to prevent the spread of electrolyte, and that in most circumstances there is little advantage to methods for designating the 3-D coordinates of an electrode that have a measurement error of less than 1 cm.

Adolescent↗

High resolution evoked potential imaging of the cortical dynamics of human working memory.

High resolution evoked potentials (EPs), sampled from 115 channels and spatially sharpened with the finite element deblurring method, were recorded from 8 subjects during working memory (WM) and control tasks. The tasks required matching each stimulus with a preceding stimulus on either verbal or spatial attributes. All stimuli elicited a central P200 potential that was larger in the spatial tasks than in the verbal tasks, and larger in the WM tasks than in the control tasks. Frequent, non-matching stimuli elicited a frontal, positive peak at 305 msec that was larger in the spatial WM task relative to the other tasks. Irrespective of whether subjects attended to verbal or spatial stimulus attributes, non-matching stimuli in the WM tasks also elicited an enhanced P450 potential over the left frontal cortex, followed by a sustained potential over the superior parietal cortex. A posterior P390 potential elicited by infrequent, matching stimuli was smaller in amplitude for both spatial and verbal WM tasks compared to control tasks, as was a central prestimulus CNV. These results indicate that WM is a function of a distributed system with both task-specific and task-independent components. Lesion studies and course temporal resolution functional imaging methods, such as PET and fMRI, tend to paint a fairly static picture of the cortical regions which participate in the performance of WM tasks. In contrast, the fine-grain time resolution provided by imaging brain function with EP methods provides a dynamic picture of subsecond changes in the spatial distribution of WM effects over the course of individual trials, as well as evidence for differences in the activity elicited by matching and non-matching stimuli within sequences of trials. This information about the temporal dynamics of WM provides a critical complement to the fine-grain spatial resolution provided by other imaging modalities.

Acoustic Stimulation↗

Mapping cognitive brain function with modern high-resolution electroencephalography.

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. While electroencephalography (EEG) provides temporal resolution in the millisecond range, which would seem to make it an ideal complement to other imaging modalities, traditional EEG technology and practice provides insufficient spatial detail to identify relationships between brain electrical events and structures and functions that are visualized by magnetic resonance imaging (MRI) or positron emission tomography (PET). Recent advances overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical information from each subject's MRI, and by correcting the distortion that is caused by volume conduction of EEG signals through the skull and scalp. Along with its ability to record how brains think when performing everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

Brain↗

Towards measurement of brain function in operational environments.

In operational environments that demand sustained vigilance or that involve multiple tasks competing for limited attentional resources, continuous monitoring of the mental state of the operator could decrease the potential for serious errors and provide valuable information concerning the ergonomics of the tasks being performed. There is widespread discussion and appreciation of the basic feasibility of utilizing neurophysiological measurements to derive accurate, reliable, rapid and unobtrusive assessments of mental state. However, progress in transitioning this idea into practical applications has been impeded by the fact that at present no convenient, inexpensive and effective means exists to derive a meaningful index of brain activity outside of laboratory settings. In this paper, we review some recent advances in recording technology and signal processing methods that will help overcome this limitation. For example, rapid progress is being made in the engineering of recording systems that are small, rugged, portable and easy-to-use, and thus suitable for deployment in operational environments. Progress is also being made in the development of signal processing algorithms for detecting and correcting recording artifacts and for increasing the amount of useful information that can be derived from brain signals. Finally, results from basic research studies suggest that accurate and reliable inferences about the mental load and alertness of an individual can be derived from neurophysiological measures in a practical fashion. These research and engineering successes suggest that it is reasonable to expect that in the near term a basic enabling technology will be deployed that will permit routine measurement of brain function in operational environments.

Arousal↗

Ultraviolet disinfection of contact lenses.

To evaluate the efficacy of ultraviolet (UV) radiation as a method of disinfecting contact lenses and their storage solutions, we contaminated soft lenses (Bausch & Lomb Optima 38), rigid gas permeable (RGP) lenses (Oxyflow F-30), and their storage solutions with three common bacteria. Escherichia coli (E.c.), Staphylococcus epidermis (S.e.), and Serratia marcescens (S.m.). The storage solutions used were saline solution and RGP conditioning solution. We determined the exposure times to 253.7-nm wavelength UV radiation necessary to disinfect the contact lenses and solutions. The decimal reduction values (D values) found for UV radiation were 10 to 200 hundred times shorter than reported for currently available disinfection systems. For E.c., sterilization was attained after 100 s of exposure. For S.e. and S.m., sterilization occurred after 300 s of exposure. Different contact lens solutions transmit UV radiation to various degrees, with saline solution passing more than 90% of the UV radiation. Thus, our results indicate that UV radiation is an effective and rapid method of disinfecting contact lenses and their storage solutions.

Colony Count, Microbial↗