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Biomedical subjects

W R Chen

Publications and source records attributed to W R Chen.

At least 19 recordsLinked to original sources
PubMed2002

Selective photothermal interaction using an 805-nm diode laser and indocyanine green in gel phantom and chicken breast tissue.

Laser immunotherapy, a novel therapy for breast cancer, utilises selective photothermal interaction to raise the temperature of tumour tissue above the cell damage threshold. Photothermal interaction is achieved with intratumoral injection of a laser-absorbing dye followed by non-invasive laser irradiation. When tumour heating is used in combination with immunoadjuvant to stimulate an immune response, antitumour immunity can be achieved. In this study, the selective photothermal effect was investigated using gel phantom and chicken breast tissue. An 805-nm diode laser and indocyanine green (ICG) were used. An ICG-containing gelatin phantom was constructed to simulate targeted tumour tissue. The target gel was buried inside chicken breast tissue and the tissue-gel construct was irradiated by the laser. Temperatures at different locations in the construct were measured during the laser irradiation. For comparison, the thermal effect of an Nd:YAG laser on the tissue-gel construct was also investigated. Selective heating of target gel containing 0.27% ICG and buried 1 cm below the chicken tissue surface was achieved with the 805-nm diode laser using a power of 0.85 W and beam radius of 1 cm. The target gel experienced a temperature increase of more then 6 degrees C whereas the surrounding chicken breast tissue experienced only a minor temperature increase. The feasibility of this experimental set-up has been shown. It will be used in the future to optimise treatment parameters such as laser power, laser beam radius, and dye concentration.

Animals↗
PubMed2002

Observation of a re-entrant kinetic glass transition in a micellar system with temperature-dependent attractive interaction.

We detect in a tri-block co-polymer micellar system an ergodic-to-nonergodic-to-ergodic transition, as a function of temperature, in a range of concentrations, by photon correlation measurements. The shear viscosity is also shown to jump two order of magnitude at these transition temperatures. Surprisingly, the structure factor as measured by small angle neutron scattering shows a marked narrowing at the structural arrest state. Rationalization of these results with the existence of an attractive branch in the phase diagram of an attractive colloid system predicted by mode coupling theory is made.

Journal Article↗
PubMed2001

Antitumor immunity induced by laser immunotherapy and its adoptive transfer.

The ideal cancer treatment modality should not only cause tumor regression and eradication but also induce a systemic antitumor immunity, which is essential for control of metastatic tumors and for long-term tumor resistance. Laser immunotherapy using a laser, a laser-absorbing dye, and an immunoadjuvant has induced such long-term immunity in treatment of a mammary metastatic tumor. The successfully treated rats established total resistance to multiple subsequent tumor challenges. To further study the mechanisms of the antitumor immunity induced by this novel treatment modality, passive adoptive transfer was performed using splenocytes as immune cells. The spleen cells that were harvested from successfully treated tumor-bearing rats provided 100% immunity in the naive recipients. The passively protected first cohort rats were immune to tumor challenge with an increased tumor dose; their splenocytes also prevented the establishment of tumor in the second cohort of naive recipient rats. This immunity transfer was accomplished without the usually required T-cell suppression in recipients.

Animals↗
PubMed2001

Localization error analysis for stereo X-ray image guidance with probability method.

The mean value and standard deviation of localization error for the stereo imaging systems are derived based on probability theory. Compared with the maximum error analysis method used in our previous study, the new approach yields more informative and precise results as the guidance for X-ray imaging system design and protocol optimization. The prototype for our current study is a CCD based monoplane digital stereo X-ray imaging system. The imaging model consists of two X-ray sources and one detector plane. With perspective geometry, the least-square solution is derived to reconstruct 3-dimensional object points, such as a biopsy needle tip, from a pair of 2-dimensional digital radiographs. Under the conditions of our specific prototype, the measurement errors of interested points in the radiographs are modeled as random variables with Gaussian distribution. Such variables account for finite image system noise and positioning errors. Then, the 3D localization error, in terms of mean value and standard deviation, is formulated using measurement error, feature point location, and separation between the two X-ray sources and distance from source to detector. Both theoretical analysis and numerical simulation are performed. The mean value and standard deviation of the localization error are first evaluated using numerical simulation under practical imaging conditions. Then, the error estimates are given in simply analytic forms. Simulation and theoretical results are in excellent agreement. The results show that our prototype X-ray stereological imaging system is accurate and reliable to locate feature points in 3D for medical intervention. Imaging protocols can be effectively optimized through the 3D localization error analysis using the approximate formulas proposed in this study.

Algorithms↗
PubMed2001

Serial changes of cardiac troponin-I in acute myoischemia induced by exercise treadmill test.

Cardiac troponin-I (cTn-I) is a sensitive and specific marker for the diagnosis of acute myocardial infarction (AMI). However, elevation of serum cTn-I has been observed in some unstable angina patients who have a worse prognosis than those with normal serum cTn-I levels. It is unknown whether serum cTn-I can elevate in stable angina patients with acute ischemic burden. Therefore, the purpose of this study was to determine a serial change of cTn-I in patients with acute ischemia induced by a treadmill exercise test. Thirty-five patients suspected of having coronary artery disease and five healthy medical students were enrolled into this study. Every patient received a treadmill exercise test. Cardiac troponin-I was measured by fluorescent immunoassay before the treadmill test and at 5 minutes, 1 hour, 3 hours, and 6 hours after the treadmill test. Patients with cTn-I levels of less than 0.5 ng/ml were considered normal, and those with cTn-I levels of greater than 2.0 ng/ml was considered to have AMI. The exercise test was positive in 19 of the 35 patients and negative in 16 of the 35 patients and 5 medical students. Among the 19 patients with positive treadmill exercise test, the cTn-I concentrations were abnormally increased in 7/19 (37%) patients (mean: 1.1 +/- 0.4 ng/ml; range: 0.5 to 2.0 ng/ml). One of the 16 patients with negative treadmill test showed an increase of serum cTn-I. Normal cTn-I levels were found in the other 15 patients and the 5 medical students. In conclusion, serum cTn-I levels were found to increase to some extent in one third of stable angina patients who have an acute ischemic episode induced by treadmill exercise test.

Aged↗
PubMed2001

Serum antioxidant status of civil aircrew.

Objective. To study the serum antioxidant status in civil aircrew members who had more than 4000 h of cumulative flight hours, therefore exposed to a higher dose of cosmic radiation comparing to the dose received by ground residents. Method. Differences in the serum levels of total antioxidant capacity (TAOC), superoxide dismutase (SOD) and malondialdehyde (MDA) were investigated in 230 crew members, 37 local ground residents in Xinjiang, and 37 ground residents in Tianjin. Result. Significantly higher levels of all the three serum indexes were found in civil aircrew members. Serum levels of TAOC and SOD were higher in Xinjiang than in Tianjin ground residents, although no difference was found for MDA. Positive correlations were observed among the three serum indexes in this study. Conclusion. The elevated serum level of MDA in civil aircrew members deserves a proper attention by health care policy makers.

Adult↗
PubMed2000

Analysis of relations between NMDA receptors and GABA release at olfactory bulb reciprocal synapses.

In the mammalian olfactory bulb, signal processing is mediated by synaptic interactions between dendrites. Glutamate released from mitral cell dendrites excites dendritic spines of granule cells, which in turn release GABA back onto the mitral cell dendrites, forming a reciprocal synaptic pair. This feedback synaptic circuit was shown to be mediated predominantly by NMDA receptors. We further utilized caged Ca2+ compounds to obtain insight into the mechanism that couples NMDA receptor activation to GABA release. Feedback inhibition elicited by photo-release of caged Ca2+ in mitral cell secondary dendrites persisted when voltage-gated Ca2+ channels were blocked by cadmium (Cd2+) and nickel (Ni2+). These results indicate that Ca2+ influx through NMDA receptors can directly trigger presynaptic GABA release for local dendrodendritic feedback inhibition.

2-Amino-5-phosphonovalerate↗
PubMed2000

Lens distortion in optically coupled digital x-ray imaging.

UNLABELLED: The objectives of this research are to analyze geometrical distortions introduced by relay lenses in optically coupled digital x-ray imaging systems and to introduce an algorithm to correct such distortions. METHODS: The radial and tangential errors introduced by a relay lens in digital x-ray imaging were experimentally measured, using a lens-coupled CCD (charge coupled device) prototype. An algorithm was introduced to correct these distortions. Based on an x-ray image of a standard calibration grid, the algorithm first identified the location of the optical axis, then corrected the radial and tangential distortions using polynomial transformation technique. RESULTS: Lens distortions were classified and both radial and tangential distortions introduced by lenses were corrected using polynomial transformation. For the specific lens-CCD prototype investigated, the mean positional error caused by the relay lens was reduced by the correction algorithm from about eight pixels (0.69 mm) to less than 1.8 pixels (0.15 mm). Our investigation also shows that the fourth order of polynomial for the correction algorithm provided the best correction result. CONCLUSIONS: Lens distortions should be considered in position-dependent, quantitative x-ray imaging and such distortions can be minimized in CCD x-ray imaging by appropriate algorithm, as demonstrated in this paper.

Algorithms↗
PubMed1999

Electrophysiological characterization of rat and mouse olfactory receptor neurons from an intact epithelial preparation.

To understand the coding mechanisms underlying olfactory discrimination, it is necessary to characterize odor response properties of olfactory receptor neurons (ORNs). In contrast with rapid progress in molecular biology, there is little physiological data from ORNs in rodent. To facilitate acquisition of such data, we have developed an intact olfactory epithelial preparation from both rat and mouse. We have carried out initial studies of this preparation by monitoring odor responses by patch-clamping directly on the ORN dendritic knobs, a subcellular site very close to the locus of olfactory signal transduction. Our results show that rat and mouse ORNs have similar intrinsic membrane properties. Most cells fired spontaneously at a low frequency (f) and about one half fired repetitively in response to current (I) injection with a linear f/I relation. About one third of rat and mouse ORNs responded to a mixture of four odors in a dose-dependent manner and about 60% of them responded to IBMX, a potent inhibitor of phosphodiesterase. The results suggest that this intact preparation offers the advantage of approximating in vivo physiological conditions, while furnishing an opportunity to map single neuron responses in the epithelium in a spatially-defined manner, using electrophysiological or cell imaging methods.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Long-term tumor resistance induced by laser photo-immunotherapy.

An ideal treatment modality for metastasizing tumors should eradicate the primary tumor and elicit a systemic, tumor-selective response leading to elimination of metastases and long-term tumor resistance. Also, it should be induced by local treatment at the primary site, to limit adverse systemic effects. A new method for treating metastatic tumors which utilizes a combination of a near-infrared laser, a photosensitizer and an immunoadjuvant has been developed. It involves intra-tumor injection of the sensitizer/adjuvant solution, followed by local non-invasive laser irradiation. It has produced regression and total eradication of treated primary tumors and untreated metastases at remote sites against mammary tumors in rats. Successfully treated tumor-bearing rats showed total tumor resistance to subsequent tumor rechallenge. Our histochemical results showed that sera from cured tumor-bearing rats contained antibodies that bound strongly to the plasma membrane of both living and preserved tumor cells. Western blot analysis of tumor cell proteins using sera from successfully treated rats as the source of primary antibodies also showed distinct bands, indicating induction of tumor-selective antibodies. Our findings indicate that a systemic, long-term effect on metastatic tumors can be induced by local application of laser photo-immunotherapy.

Adjuvants, Immunologic↗
PubMed1999

Measurement of x-ray attenuation coefficients of aqueous solutions of indocyanine green and glycated chitosan.

We report our experimental results of measurements of x-ray attenuation coefficients of aqueous solutions of a light absorbing dye, indocyanine green, and an immunoadjuvant, glycated chitosan. In the treatment of metastatic tumors in rats using a novel laser immunotherapy these solutions were administered in situ. The x-ray attenuation data of the solutions are essential to development of an x-ray digital imaging system for monitoring the administration of the solution, as well as for the distribution and the diffusion of the solution in tumors and in surrounding tissue. The composition of the solutions, the measurement system configuration, and the technique used to determine the attenuation coefficients are described. The experimental results show that glycated chitosan has a higher attenuation coefficient compared to indocyanine green and water. Our experimental data proved that, even at low concentrations, the x-ray attenuation through these aqueous solutions could be differentiated. Therefore, a digital x-ray imaging technique can be used effectively in monitoring and controlling the intratumor diffusion and distributions of these solutions.

Adjuvants, Immunologic↗
PubMed1999

Synaptic organization and neurotransmitters in the rat accessory olfactory bulb.

The accessory olfactory bulb (AOB) is the first relay station in the vomeronasal system and may play a critical role in processing pheromone signals. The AOB shows similar but less distinct lamination compared with the main olfactory bulb (MOB). In this study, synaptic organization of the AOB was analyzed in slice preparations from adult rats by using both field potential and patch-clamp recordings. Stimulation of the vomeronasal nerve (VN) evoked field potentials that showed characteristic patterns in different layers of the AOB. Current source density (CSD) analysis of the field potentials revealed spatiotemporally separated loci of inward current (sinks) that represented sequential activation of different neuronal components: VN activity (period I), synaptic excitation of mitral cell apical dendrites (period II), and activation of granule cells by mitral cell basal dendrites (period III). Stimulation of the lateral olfactory tract also evoked field potentials in the AOB, which indicated antidromic activation of the mitral cells (period I and II) followed by activation of granule cells (period III). Whole cell patch recordings from mitral and granule cells of the AOB supported that mitral cells are excited by VN terminals and subsequently activate granule cells through dendrodendritic synapses. Both CSD analysis and patch recordings provided evidence that glutamate is the neurotransmitter at the vomeronasal receptor neuron; mitral cell synapses and both NMDA and non-NMDA receptors are involved. We also demonstrated electrophysiologically that reciprocal interaction between mitral and granule cells in the AOB is through the dendrodendritic reciprocal synapses. The neurotransmitter at the mitral-to-granule synapses is glutamate and at the granule-to-mitral synapse is gamma-aminobutyric acid. The synaptic interactions among receptor cell terminals, mitral cells, and granule cells in the AOB are therefore similar to those in the MOB, suggesting that processing of chemosensory information in the AOB shares similarities with that in the MOB.

Animals↗
PubMed1999

Computational analysis of action potential initiation in mitral cell soma and dendrites based on dual patch recordings.

In olfactory mitral cells, dual patch recordings show that the site of action potential initiation can shift between soma and distal primary dendrite and that the shift is dependent on the location and strength of electrode current injection. We have analyzed the mechanisms underlying this shift, using a model of the mitral cell that takes advantage of the constraints available from the two recording sites. Starting with homogeneous Hodgkin-Huxley-like Na(+)-K(+) channel distribution in the soma-dendritic region and much higher sodium channel density in the axonal region, the model's channel kinetics and density were adjusted by a fitting algorithm so that the model response was virtually identical to the experimental data. The combination of loading effects and much higher sodium channel density in the axon relative to the soma-dendritic region results in significantly lower "voltage threshold" for action potential initiation in the axon; the axon therefore fires first unless the voltage gradient in the primary dendrite is steep enough for it to reach its higher threshold. The results thus provide a quantitative explanation for the stimulus strength and position dependence of the site of action potential initiation in the mitral cell.

Action Potentials↗
PubMed1997

Forward and backward propagation of dendritic impulses and their synaptic control in mitral cells.

The site of impulse initiation is crucial for the integrative actions of mammalian central neurons, but this question is currently controversial. Some recent studies support classical evidence that the impulse always arises in the soma-axon hillock region, with back-propagation through excitable dendrites, whereas others indicate that the dendrites are sufficiently excitable to initiate impulses that propagate forward along the dendrite to the soma-axon hillock. This issue has been addressed in the olfactory mitral cell, in which excitatory synaptic input is restricted to the distal tuft of a single primary dendrite. In rat olfactory bulb slices, dual whole cell recordings were made at or near the soma and from distal sites on the primary dendrite. The results show that the impulse can be initiated in either the soma-axon hillock or in the distal primary dendrite, and that the initiation site is controlled physiologically by the excitatory synaptic inputs to the distal tuft and inhibitory synaptic inputs near the soma.

Action Potentials↗
PubMed1997

Laser-photosensitizer assisted immunotherapy: a novel modality for cancer treatment.

Photosensitizer-enhanced laser treatment, where dyes are activated in situ by lasers of appropriate wavelengths, provides highly selective tissue destruction, both spatially and temporally, through photophysical reactions. Although laser-sensitizer treatment for cancer can achieve a controlled local tumor cell destruction on a large scale, total tumor eradication may not be accomplished because of the incomplete local tumor killing or the presence of tumor metastases, or both. The long-term control of cancer depends on the host immune surveillance and defense systems in which both cell-mediated and humoral responses are critical. In this study we report a novel minimally invasive cancer treatment combining the laser photophysical effects with the photobiological effects. Irradiation of a rat mammary tumor by an 805 nm diode laser, after an intratumor administration of a specific photosensitizer, indocyanine green in a glycated chitosan gel, caused immediate photothermal destruction of neoplastic cells. Concomitantly this treatment stimulated the immunological defense system against residual and metastatic tumor cells. Increases in survival rate and in the eradication of tumor burden, both primary and metastatic, were observed after this treatment. Furthermore, the resistance of successfully treated rats to tumor rechallenge demonstrated a long-lasting systemic effect of the treatment. These findings indicate that our treatment has triggered a specific humoral immune response in the tumor-bearing rats.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Membrane and synaptic properties of mitral cells in slices of rat olfactory bulb.

We have investigated the membrane properties and excitatory synaptic transmission of mitral cells in a slice preparation of rat olfactory bulb. In response to intracellular injection of depolarizing current, most mitral cells showed several distinct membrane properties: (1) delayed onset of firing (suggesting the presence of a type of potassium A current); (2) subthreshold oscillation of the membrane potential; and (3) repetitive firing of clustered action potentials during prolonged threshold stimulation. Olfactory nerve (ON) stimulation evoked a long-lasting EPSP in most of the mitral cells. This long EPSP was completely blocked by combined application of NMDA and non-NMDA receptor antagonists (20 microM CNQX and 100 microM APV), confirming that glutamate is the neurotransmitter at the synapses from ON to mitral cells. The ON-evoked EPSP was preceded by a prespike, which was resistant to membrane potential hyperpolarization at the soma. This fast prepotential may be indicative of an active response in the primary dendritic tufts of the mitral cells. Stimulation of the lateral olfactory tract evoked an antidromic pulse followed by a short EPSP, which could also be elicited independently of an antidromic spike in the recorded cell. Since the asymmetrical synapses so far observed on the mitral cells are all form the ON, this antidromically evoked EPSP may reflect self-excitation of a mitral cell by glutamate released from its own dendrites by antidromic impulse invasion, or/and lateral excitation by neighboring invaded dendrites.

2-Amino-5-phosphonovalerate↗
PubMed1996

Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex.

The primate temporal cortex has been demonstrated to play an important role in visual memory and pattern recognition. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here we address this issue by examining the induction of synaptic plasticity in surgically resected human inferior and middle temporal cortex. The results show that synaptic strength in the human temporal cortex could undergo bidirectional modifications, depending on the pattern of conditioning stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long-term potentiation (LTP) of both intracellular excitatory postsynaptic potentials and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that N-methyl-D-aspartate receptors were responsible for its induction. Long-term depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15 min). It was reduced, but not completely blocked, by DL-2-amino-5-phosphonovaleric acid, implying that some other mechanisms in addition to N-methyl-DL-aspartate receptors were involved in LTD induction. LTD was input-specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic transmission in that pathway only. Finally, the LTP and LTD could reverse each other, suggesting that they can act cooperatively to modify the functional state of cortical network. These results suggest that LTP and LTD are possible mechanisms for the visual memory and pattern recognition functions performed in the human temporal cortex.

2-Amino-5-phosphonovalerate↗