Biomedical subjects
Publications and source records attributed to M Dai.
We report limitation of gaze and slow saccadic eye movements by clinical examination and video-oculography in a patient with Becker muscular dystrophy. This rare association suggests that a dystrophinopathy should be considered in a patient with features characteristic of Becker muscular dystrophy even when mild impairment of eye movements is present.
1. We studied the contribution of the individual semicircular canals to the generation of horizontal and torsional eye movements in cynomolgus monkeys. Eye movements were elicited by sinusoidal rotation about a vertical (gravitational) axis at 0.2 Hz with the animals tilted in various attitudes of static forward or backward pitch. The gains of the horizontal and torsional components of the vestibuloocular reflex (VOR) were measured for each tilt position. The gains as a function of tilt position were fit with sinusoidal functions, and spatial gains and phases were determined. After control responses were recorded, the semicircular canals were plugged, animals were allowed to adapt, and the test procedure was repeated. Animals were prepared with only the anterior and posterior canals intact [vertical canal (VC) animals], with only the lateral canals intact [lateral canal (LC) animal], and with only one anterior and the contralateral posterior canals intact [right anterior and left posterior canal (RALP) animals; left anterior and right posterior canal (LARP) animals]. 2. In normal animals, the gain of the horizontal (yaw axis) velocity of the compensatory eye movements decreased as they were pitched forward or backward, and a torsional velocity appeared, reversing phase at the peak of the horizontal gain. After the anterior and posterior canals were plugged (LC animal), the horizontal component was reduced when the animal was tilted backward; the gain was zero with about -60 degrees of backward tilt. The spatial phase of the torsional component had the same characteristics. This is consistent with the fact that both responses were produced by the lateral canals, which from our results are tilted between 28 and 39 degrees above the horizontal stereotaxic plane. 3. After both lateral canals were plugged (VC animals), horizontal velocity was reduced in the upright position but increased as the animals were pitched backward relative to the axis of rotation. Torsional velocities, which were zero in the upright position in the normal animal, were now 180 degrees out of phase with the horizontal velocity. The peak values of the horizontal and torsional components were significantly shifted from the normal data and were closely aligned with each other, reaching peak values at approximately -56 degrees pitched back (-53 degrees horizontal, -58 degrees torsional). The same was true for the LARP and RALP animals; the peak values were at -59 degrees pitched back (-55 degrees horizontal, -62 degrees torsional). Likewise, in the LC animal the peak yaw and roll gains occurred at about the same angle of forward tilt, 35 degrees (30 degrees horizontal, 39 degrees torsional). Thus, in each case, the canal plugging had transformed the VOR from a compensatory to a direction-fixed response with regard to the head. Therefore there was no adaptation of the response planes of the individual canals after plugging. 4. The data were compared with eye velocity predictions of a model based on the geometric organization of the canals and their relation to a head coordinate frame. The model used the normal to the canal planes to form a nonorthogonal coordinate basis for representing eye velocity. An analysis of variance was used to define the goodness of fit of model predictions to the data. Model predictions and experimental data agreed closely for both normal animals and for the animals with canal lesions. Moreover, if horizontal and roll components from the LC and VC animals were combined, the summation overlay the response of the normal monkeys and the predictions of the model. In addition, a combination of the RALP and LARP animals predicted the response of the lateral-canal-plugged (VC) animals. 5. When operated animals were tested in light, the gains, peak values, and spatial phases of horizontal and roll eye velocity returned to the preoperative values, regardless of the type of surgery performed. This indicates that vision compensated for the lack o
In order to maintain the effective fixation effect of rigid bone plate in the early stage of fracture and to prevent osteoporosis induced by stress shielding effect of rigid plate in later stage of fixation, a washer made of viscoelastic material was placed between the screw and the screw hole of plate to form a stress-relaxation plate system. Both in vitro and in vivo experiments demonstrated that there was no statistical difference between the stress shielding effect of padded and unpadded plate groups. The washer showed significant deformation and damaged 8 weeks after implantation, and 10 weeks after implantation the stress shielding rate of the padded plate group was significantly lower than that of the unpadded group (P < 0.05). As a consequence, the degree of osteoporosis of the tibia in the padded group was significantly milder than the unpadded group, and 20 weeks after implantation, the diameter of the tibia medullary cavity of the padded group was significantly smaller than that of the unpadded group. The thickness of cortical bone and the bending strength of the tibia of padded group were significantly larger than those of the unpadded group (P < 0.05-0.01). These results showed that the stress-relaxation plate system can effectively maintain the stability of fracture fixation at the similar level of rigid plate during the early stage of fracture and can gradually lower down the stress shielding rate so as to prevent severe osteoporosis and reduction of bone mechanical property in the later stage of fixation.
The present study has shown that Guizhi Decoction can increase the normal myocardial blood flow in rabbits. The best result can be achieved in twenty minutes after the decoction is given (ig).
An ideal bone plate would provide rigid fixation to ensure stabilization of bone fragments at the early stage after fracture, while at the late stage osteoporosis induced by stress shielding effect of the plate should be prevented. However, there is no report of such a plate that could meet with all these requirements. Twenty-eight adult New Zealand rabbits were used in this experiment. Ordinary stainless-steel plate (no washer plate) and similar plate padded with ultrahigh molecular polyethylene washers in its screw holes (washer plate) were fixed respectively on mid-shelf of each side of tibiae. The animals were killed at 2, 4, 8, 12, 16, 20 and 24 weeks after operation, and the fixed bone segments of both tibiae were removed for light microscopy, polarized light microscopy and fluoroscopy. The results showed that the tibiae fixed with plate fixation both appeared bone resorption, but there was more severe resorption in bone with no washer plate fixation than that with washer plate fixation. Cancelization of cortical bone was seen in the former but not in the latter at 12 weeks postopertively. This demonstrated that the washer might creep and damage with fixation time, resulting in gradual decrease in the rigidity of the plate-screw system and thus reducing bone resorption as caused by stress shielding.
We recorded the horizontal (yaw), vertical (pitch), and torsional (roll) eye movements of two rhesus monkeys with scleral search coils before and after the COSMOS Biosatellite 2229 Flight. The aim was to determine effects of adaptation to microgravity on the vestibulo-ocular reflex (VOR). The animals flew for 11 days. The first postflight tests were 22 h and 55 h after landing, and testing extended for 11 days after reentry. There were four significant effects of spaceflight on functions related to spatial orientation: (1) Compensatory ocular counterrolling (OCR) was reduced by about 70% for static and dynamic head tilts with regard to gravity. The reduction in OCR persisted in the two animals throughout postflight testing. (2) The gain of the torsional component of the angular VOR (roll VOR) was decreased by 15% and 50% in the two animals over the same period. (3) An up-down asymmetry of nystagmus, present in the two monkeys before flight was reduced after exposure to microgravity. (4) The spatial orientation of velocity storage was shifted in the one monkey that could be tested soon after flight. Before flight, the yaw axis eigenvector of optokinetic afternystagmus was close to gravity when the animal was upright or tilted. After flight, the yaw orientation vector was shifted toward the body yaw axis. By 7 days after recovery, it had reverted to a gravitational orientation. We postulate that spaceflight causes changes in the vestibular system which reflect adaptation of spatial orientation from a gravitational to a body frame of reference. These changes are likely to play a role in the postural, locomotor, and gaze instability demonstrated on reentry after spaceflight.
Metastasizing cancer cells can invade the extracellular matrix using plasma membrane protrusions, termed invadopodia, that contact and dissolve the matrix. Various membrane associated proteases localized on the invadopodial membranes are responsible for the extracellular matrix degradation. Work from our laboratory shows that secreted proteases including Gelatinase A, and high molecular weight integral membrane proteases are associated with cell surface invadopodia. Three cell types, including chicken embryonic cells transformed by Rous sarcoma virus, human malignant melanoma cell line LOX, and human breast carcinoma cell line MDA-MB-231, retain the invasive phenotype in vitro, express invadopodia, degrade and enter into a fibronectin-rich collagenous matrix. We suggest that invadopodium-associated proteases are ideal targets for the diagnosis and treatment of cancer as their presence in association with primary tumors may signal increased metastatic potential. An approach toward the development of new prognostic markers for breast malignancy involved production of monoclonal antibodies directed against membrane proteases in a mixture of glycoproteins. Double immunofluorescent technique using a known invadopodium marker is designed to select specific monoclonal antibodies colocalizing at the invasion front, on invadopodia of cancer cells. Membrane protease accessibility at the cell surface can therefore be exploited for therapeutic advances by the development of specific antibodies and inhibitors that block their activities, and by the use of monoclonal antibodies to target cytotoxic molecules to micrometastases. Also, this same accessibility may potentially be used to detect surface proteases on micrometastases or to detect components shed by micrometastases in serum.
Corneal endothelial wound healing in living rabbit eyes after mechanical scrape (MS) and transcorneal freeze (TCF) injury was studied using tandem scanning confocal microscopy (TSCM). MS injury was created on the central corneal endothelium with an olive tip cannula; TCF injury was created using a 3-mm-diameter stainless steel probe cooled with liquid nitrogen. In vivo observation of wound healing using TSCM was correlated with scanning electron microscopy (SEM) for fixed tissues. At 6 h after MS, migrating endothelial cells at the leading edge showed lamellipodial processes on in vivo TSCM and SEM. After 24 h, the denuded area was almost fully resurfaced by migrating endothelial cells showing wide spaces between nuclei by TSCM. After 28 days, resurfaced endothelial cells showed normal hexagonal mosaic appearance with enlarged cells by TSCM and SEM. TCF injury produced fibroblastic changes in the endothelial cells with elongation and spreading by 24 h after injury. After 3 days, the wounded area was resurfaced with two cell types: (a) migrating endothelial cells at the peripheral area, which appeared polygonal in shape with wide intracellular spaces and (b) fibroblast-like cells at the center of the wound, which formed a retrocorneal fibrous membrane (RCFM). The RCFM was posteriorly covered with normal endothelium after 28-60 days. TSCM of the stroma demonstrated spindle-shaped, activated keratocytes migrating into the wounded stroma at 3-14 days. In conclusion, TSCM allows viewing of dynamic four-dimensional morphologic changes (x, y, z, and time) during in vivo cellular repair of corneal wound healing after either MS or TCF injury.
PURPOSE: To compare and contrast the in vivo mechanism of wound healing after mechanical scrape and transcorneal freeze (TCF) injury in a rabbit eye model by examining changes in the cytoskeletal organization of contractile, filamentous actin (f-actin) microfilaments as relates to differences in cell migration or translocation during endothelial repair. METHODS: Endothelial wound healing after mechanical scrape and transcorneal freeze injury was studied in rabbit eyes using laser scanning confocal microscopy (LSCM). Central corneal mechanical scrape injury was made using an olive tip cannula, and TCF injury was made using a 3-mm diameter stainless steel probe cooled with liquid nitrogen. Cytoskeletal changes in f-actin stained with phalloidin-FITC were observed during wound healing using LSCM. RESULTS: At 6 hours after mechanical scrape, the leading edge of the migrating sheet showed a decrease in the intensity of phalloidin-FITC staining, suggesting a decrease in cortical f-actin. Migrating endothelial cells in vivo did not appear to develop stress fibers after mechanical scrape, which is consistent with an in vitro cell spreading mechanism of endothelial wound healing. By 24 hours, the denuded area was almost fully resurfaced by migrating endothelial cells. On the other hand, TCF injury produced fibroblastic changes in the endothelial cells with extension and elongation of spindle-shaped endothelial cells at the leading edge by 24 hours after injury. Fibroblastic endothelial cells developed prominent actin stress-fibers, which is consistent with an in vitro cell migration mechanism of endothelial wound healing. Three days after TCF, the wounded area was resurfaced with two cell types: rough, fibroblast-like cells forming a retrocorneal fibrous membrane having prominent f-actin bundles or stress fibers with few cell-cell junctions, and smooth, polygonal-shaped endothelial cells having tight cell junctions with a cortical distribution of f-actin. After 28 days the retrocorneal fibrous membrane was posteriorly covered with normal endothelium. CONCLUSIONS: These data support the hypothesis that endothelial wound healing involves two separate, injury-dependent, mechanisms--cell spreading and cell migration.
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1. A simplified three-dimensional state space model of visual vestibular interaction was formulated. Matrix and dynamical system operators representing coupling from the semicircular canals and the visual system to the velocity storage integrator were incorporated into the model. 2. It was postulated that the system matrix for a tilted position was a composition of two linear transformations of the system matrix for the upright position. One transformation modifies the eigenvalues of the system matrix while another rotates the pitch and roll eigenvectors with the head, while maintaining the yaw axis eigenvector approximately spatially invariant. Using this representation, the response characteristics of the pitch, roll, and yaw eye velocity were obtained in terms of the eigenvalues and associated eigenvectors. 3. Using OKAN data obtained from monkeys and comparing to the model predictions, the eigenvalues and eigenvectors of the system matrix were identified as a function of tilt to the side or of tilt to the prone positions, using a modification of the Marquardt algorithm. The yaw eigenvector for right-side-down tilt and for downward pitch cross-coupling was approximately 30 degrees from the spatial vertical. For the prone position, the eigenvector was computed to be approximately 20 degrees relative to the spatial vertical. For both side-down and prone positions, oblique OKN induced along eigenvector directions generated OKAN which decayed to zero along a straight line with approximately a single time constant. This was verified by a spectral analysis of the residual sequence about the straight line fit to the decaying data. The residual sequence was associated with a narrow autocorrelation function and a wide power spectrum. 4. Parameters found using the Marquardt algorithm were incorporated into the model. Diagonal matrices in a head coordinate frame were introduced to represent the direct pathway and the coupling of the visual system to the integrator. Model simulations predicted the behavior of yaw and pitch OKN and OKAN when the animal was upright, as well as the cross-coupling in the tilted position. The trajectories in velocity space were also accurately simulated. 5. There were similarities between the monkey eigenvectors and human perception of the spatial vertical. For side-down tilts and downward eye velocity cross-coupling, there was only an Aubert (A) effect. For upward eye velocity cross-coupling there were both Müller (E) and Aubert (A) effects. The mean of the eigenvectors for upward and downward eye velocities overlay human 1 x g perceptual data.(ABSTRACT TRUNCATED AT 400 WORDS)
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The authors studied 30 patients undergoing general anesthesia in order to evaluate whether oral clonidine premedication could attenuate the hemodynamic changes associated with laryngoscopy and tracheal intubation. Patients were randomly assigned to one of two groups; clonidine group (n = 15) who received oral clonidine of approximately 5 micrograms.kg-1, or control group (n = 15) who received no clonidine. The magnitude of increases in mean blood pressure from baseline values following laryngoscopy and tracheal intubation in the clonidine group was significantly smaller as compared with that in the control group (20 +/- 12 vs. 31 +/- 14 mmHg, mean +/- SD, P less than 0.05). There was also a significant difference between the two groups in the incidence of systolic blood pressure increases above 180 mmHg following laryngoscopy and tracheal intubation (0% vs. 26%, P less than 0.05). However, no significant difference was noted between the two groups in the heart rate responses to laryngoscopy and tracheal intubation. It is concluded that oral clonidine of 5 micrograms.kg-1 as a preanesthetic medication could attenuate the pressor responses associated with laryngoscopy and tracheal intubation.