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Biomedical subjects

A M Wong

Publications and source records attributed to A M Wong.

At least 19 recordsLinked to original sources

Anti-inflammatory mechanisms of dietary restriction in slowing aging processes.

Dietary restriction (DR) remains the most powerful and general environmental manipulation of aging processes in laboratory animals with strong beneficial effects on most age-related degenerative changes throughout the body. Underlying the beneficial effects of DR is the attenuation of system-wide inflammatory processes including those occurring within the central nervous system. During normal aging a progressive neuroinflammatory state builds in the brain involving astrocytes and microglia, the primary cellular components of neuroinflammation. DR attenuates the age-related activation of astrocytes and microglia with concomitant beneficial effects on neurodegeneration and cognition. Increasing evidence suggests that common pathways are emerging that link many normal aging inflammatory processes with age-related diseases such as Alzheimer, cancer, diabetes and cardiovascular disease.

Aging↗

Proprioceptive role for palisade endings in extraocular muscles: evidence from the Jendrassik Maneuver.

A proprioceptive hypothesis for the control of eye movements has been recently proposed based on neuroanatomical tracing studies. It has been suggested that the non-twitch motoneurons could be involved in modulating the gain of sensory feedback from the eye muscles analogous to the gamma (gamma) motoneurons which control the gain of proprioceptive feedback in skeletal muscles. We conducted behavioral and psychophysical experiments to test the above hypothesis using the Jendrassik Maneuver (JM) to alter the activity of gamma motoneurons. It was hypothesized that the JM would alter the proprioceptive feedback from the eye muscles which would result in misregistration of eye position and mislocalization of targets. In the first experiment, vergence eye movements and pointing responses were examined. Data showed that the JM affected the localization responses but not the actual eye position. Perceptual judgments were tested in the second experiment, and the results showed that targets were perceived as farther when the afferent feedback was altered by the JM. Overall, the results from the two experiments showed that eye position was perceived as more divergent with the JM, but the actual eye movements were not affected. We tested this further in Experiment 3 by examining the effect of JM on the amplitude and velocity of saccadic eye movements. As expected, there were no significant differences in saccadic parameters between the control and experimental conditions. Overall, the present study provides novel insight into the mechanism which may be involved in the use of sensory feedback from the eye muscles. Data from the first two experiments support the hypothesis that the JM alters the registered eye position, as evidenced by the localization errors. We propose that the altered eye position signal is due to the effect of the JM which changes the gain of the sensory feedback from the eye muscles, possibly via the activity of non-twitch motoneurons.

Adult↗

Eye-movement responses to disparity vergence stimuli with artificial monocular scotomas.

The effects of artificial monocular scotomas on eye-movement responses to horizontal disparity vergence stimuli were studied in six subjects with normal binocular vision. Subjects viewed stereoscopic 1.5 degrees horizontal step disparity vergence stimuli through liquid crystal shutter glasses. The central portion of the stimulus presented to the right eye was removed to simulate monocular artificial scotomas of variable diameters (2 degrees to 10 degrees ). Eye movements were recorded with a binocular head-mounted eye tracker. Responses included pure vergence, vergence followed by saccades, and pure saccadic eye movements. The rate of responses with saccadic eye movements increased with the diameter of the artificial scotoma (p < 0.0001); there was an increase in the rate of responses starting with saccades (p < 0.0001), as well as an increase in the rate of saccades after initial vergence responses (p < 0.01). The probability of saccades after initial vergence responses was affected by the open-loop gain of the vergence response (p < 0.001). The open-loop gain decreased with increased diameters of the artificial scotomas (p < 0.0001). As the diameter of the artificial scotomas increased, the amplitude of the initial vergence eye-movement responses decreased, and the prevalence of saccadic eye movements and asymmetric vergence increased. The effects of the diameter of artificial monocular scotomas on eye-movement responses in subjects with normal binocular vision are consistent with the effects of diameter of suppression scotomas on eye-movement responses to disparity vergence stimuli in patients with infantile esotropia.

Adolescent↗

Acute necrotizing encephalopathy of childhood: correlation of MR findings and clinical outcome.

BACKGROUND AND PURPOSE: The clinical outcome of acute necrotizing encephalopathy of childhood (ANEC), an encephalopathy characterized by symmetrical involvement of the thalami, has historically been poor, but recent studies have reported better outcomes. By devising a MR imaging scoring system, we determined the relationship between characteristic MR findings and clinical outcome of patients with ANEC. METHODS: MR studies of 12 patients with ANEC were retrospectively reviewed. A MR imaging score was calculated for each patient according to the presence of hemorrhage, cavitation, and location of lesions. Clinical outcome of the patients was assessed, yielding outcome categories based on health state utility value. Spearman rank test was used to correlate the MR imaging score with clinical outcome of the patients. RESULTS: Statistically significant correlation (r = 0.76, P = .001) was found between the MR score and the outcome category. The thalami were involved in all 12 patients, brain stem in 10, cerebral white matter in 8, and cerebellar white matter in 4. Hemorrhage was present in 5 patients and cavitation in 4. Clinical outcome category was 1 in 2 patients, 2 in 8 patients, and 3 in 2 patients. No patients were in category 4. CONCLUSION: There is a significant and positive correlation between the clinical outcome and the MR imaging score in patients with ANEC. The relation between clinical outcome and each individual MR feature remains to be determined. Patients with ANEC may have a better clinical outcome than has been previously reported.

Brain↗

Magnetic resonance imaging of carotid artery abnormalities in patients with sphenoid sinusitis.

Sphenoid sinusitis is unusual in children, but when it occurs, it can lead to serious intracranial complications. We show the value of MRI in demonstrating intracranial abnormalities due to sphenoid sinus infection, particularly those involving the internal carotid arteries and cavernous sinuses. We reviewed our imaging experience of sphenoid sinusitis and found four patients with ICA narrowing who had undergone MR evaluation including conventional and diffusion imaging. MR angiography was also performed in three patients to determine the extent of ICA narrowing. Narrowing of ICA was found in the cavernous segment in all patients and in the supraclinoid segment in three. Cerebral infarction was found in two patients. In one patient the cavernous sinus showed hyperintensity on diffusion-weighted images and hypointensity on apparent diffusion coefficient map, suggesting reduced diffusion. Although infrequent in children, sphenoid sinus infection should be considered as a possible cause of intracranial infection, particularly in teenagers. Early recognition of cavernous sinus involvement and ICA narrowing may lead to prompt treatment and hence a more favorable outcome.

Adolescent↗

Mammary glands reconstituted with Neu/ErbB2 transformed HC11 cells provide a novel orthotopic tumor model for testing anti-cancer agents.

The ErbB2 receptor tyrosine kinase (RTK) has been intensely pursued as a cancer therapy target due to its association with breast cancer. In this study we used the HC11 mammary epithelial cell line to develop an orthotopic, ErbB2-driven tumor model for testing efficacy of anti-cancer compounds. HC11 cells were infected with a retrovirus encoding oncogenic NeuT, the rat homolog of ErbB2. Drug-selected populations were introduced into mammary fat pads of Balb/c syngeneic mice cleared of host tissue. The majority of glands injected with HC11-NeuT cells developed mammary tumors which appeared after a 3-4 week latency period and grew rapidly. HC11 cells infected with the control retrovirus showed no tumor growth after injection. Tumor-bearing mice were used to compare the in vivo efficacy of two anti-cancer agents: PKI166, a kinase inhibitor selective for EGF receptor and ErbB2, and Taxol, a microtubule assembly blocker. PKI166 inhibited NeuT-induced mammary tumor growth in a dose-dependent manner and at a dose below the maximum tolerated dose (MTD) was significantly more inhibitory than Taxol at its MTD (57% vs. 25% tumor regression). Importantly, there was a dose-dependent decrease in the phosphotyrosine content of NeuT isolated from PKI166-treated, tumor-bearing mice, providing a mechanistic link between kinase inhibition and its anti-tumor activity. Thus, implantation of genetically manipulated HC11 cells into mammary glands appears to be an excellent model for studying effects of anti-cancer agents in an orthotopic site.

Animals↗

Opsoclonus in three dimensions: oculographic, neuropathologic and modelling correlates.

Opsoclonus is a dyskinesia consisting of involuntary, arrhythmic, chaotic, multidirectional saccades, without intersaccadic intervals. We used a magnetic scleral search coil technique to study opsoclonus in two patients with paraneoplastic complications of lung carcinoma. Eye movement recordings provided evidence that opsoclonus is a three-dimensional oscillation, consisting of torsional, horizontal, and vertical components. Torsional nystagmus was also present in one patient. Antineuronal antibody study revealed the presence of anti-Ta (Ma2 onco-neuronal antigen) antibodies in one patient, which had previously been associated only with paraneoplastic limbic encephalitis and brainstem dysfunction, but not opsoclonus, and only in patients with testicular or breast cancer. Neuropathologic examination revealed mild paraneoplastic encephalitis. Normal neurons identified in the nucleus raphe interpositus (rip) do not support postulated dysfunction of omnipause cells in the pathogenesis of opsoclonus. Computer simulation of a model of the saccadic system indicated that disinhibition of the oculomotor region of the fastigial nucleus (FOR) in the cerebellum can generate opsoclonus. Histopathological examination revealed inflammation and gliosis in the fastigial nucleus. This morphological finding is consistent with, but not necessary to confirm, damage to afferent projections to the FOR, as determined by the model. Malfunction of Purkinje cells in the dorsal vermis, which inhibit the FOR, may cause opsoclonus by disinhibiting it.

Afferent Pathways↗

Pulmonary function and spinal characteristics: their relationships in persons with idiopathic and postpoliomyelitic scoliosis.

OBJECTIVE: To identify what influence the various features of spinal deformity have on pulmonary function in persons with idiopathic and the postpoliomyelitic scoliosis. DESIGN: Prospective, cohort, observational study with clinical and radiologic evaluations. SETTING: Hospital-based rehabilitation units. PATIENTS: Forty-four patients with idiopathic scoliotis and 16 with postpoliomyelitic scoliotis. Each group was divided into subgroups: normal and abnormal pulmonary function. INTERVENTION: Clinical and radiologic evaluation of spinal deformity, full pulmonary functional test and respiratory muscle strength were performed. Presence of dyspnea on exertion and low back pain (LBP) was recorded. MAIN OUTCOME MEASURES: Pulmonary function: spirometry, lung volume test, and diffusing capacity. Respiratory muscle strength: maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). Presence of dyspnea on exertion (DOE), and LBP were also recorded. Characteristics of spinal deformity: direction of convexity, uppermost vertebra, number of involved vertebrae, Cobb angle, the apical vertebra, degree of rotation at the apical vertebra, type of scoliotic curve, and presence of balanced spine and pelvic obliquity. Chi-square analyses and Mann-Whitney U test for between-groups comparisons. Spearman's rho correlation coefficient to determine the existence and magnitude of a relationship. RESULTS: We found significant differences between the idiopathic and postpoliomyelitis groups in the degree of rotation at the apical vertebra, MIP, average percentage of predicted vital capacity, residual volume/total lung capacity, presence of double or triple curves, pelvic obliquity, and DOE. Between the idiopathic scoliotis subgroups we found significant differences in the uppermost vertebra and number of vertebrae in the scoliotic curve. Between the subgroups of the postpoliomyelitis group were significant differences in the location of the apical vertebra and the uppermost vertebral body of scoliotic curve. In the idiopathic group, pulmonary function was mostly related to scoliotic angle, number of vertebrae in the scoliotic curve, location of the uppermost vertebra, and the patients' age; MIP and MEP were negatively related to the scoliotic angle and degree of rotation of apical vertebra. In the postpoliomyelitis group, pulmonary function was mostly related to scoliotic angle, kyphotic angle, location of the uppermost vertebra of the scoliotic curve, and age. CONCLUSION: No single factor can predict the severity of impairment in scoliotic patients' pulmonary function. In both groups, severity of pulmonary impairment was related to the combined features of the spinal deformity. However, uppermost vertebra, scoliotic angle, and patient's age may play important roles influencing pulmonary function in both groups.

Adult↗

Coordination exercise and postural stability in elderly people: Effect of Tai Chi Chuan.

OBJECTIVE: To evaluate the effects of coordination exercise on postural stability in older individuals by Chinese shadow boxing, Tai Chi Chuan (TCC). DESIGN: Cross-sectional study. SETTING: Research project in a hospital-based biomechanical laboratory. PARTICIPANTS: The TCC group (n = 25) had been practicing TCC regularly for 2 to 35 years. The control group (n = 14) included healthy and active older subjects. INTERVENTION: Static postural stability test: progressively harder sequential tests with 6 combinations of vision (eyes open, eyes closed, sway-referenced) and support (fixed, sway-referenced); and dynamic balance test: 3 tests of weight shifting (left to right, forward-backward, multidirectional) at 3 speeds. MAIN OUTCOME MEASURES: Static and dynamic balance of Sensory Organization Testing (SOT) of the Smart Balance Master System. RESULTS: In static postural control, the results showed no differences between the TCC or control group in the more simple conditions, but in the more complicated SOT (eyes closed with sway surface, sway vision with sway surface), the TCC group had significantly better results than the control group. The TCC group also had significantly better results in the rhythmic forward-backward weight-shifting test. Duration of practice did not seem to affect the stability of elder people. CONCLUSION: The elderly people who regularly practiced TCC showed better postural stability in the more challenged conditions than those who do not (eg, the condition with simultaneous disturbance of vision and proprioception). TCC as a coordination exercise may reduce the risk of a fall through maintaining the ability of posture control.

Adolescent↗

Symmetrical body-weight distribution training in stroke patients and its effect on fall prevention.

OBJECTIVE: To determine the role of symmetrical body-weight distribution training in preventing falls among patients with hemiplegic stroke. DESIGN: A prospective study using a standing biofeedback trainer. SETTING: Hospital-based rehabilitation units. PATIENTS: Fifty-four patients with hemiplegic stroke (30 in the training group, 24 in the control group). INTERVENTIONS: Conventional stroke rehabilitation program, plus symmetrical standing training and repetitive sit-to-stand training, with a standing biofeedback trainer. Training effect was evaluated by assessing the sit-to-stand performance and comparing the occurrence of falls in the 2 groups at a 6-month follow-up. MAIN OUTCOME MEASURES: Occurrence of falls, sit-to-stand performance, including body-weight distribution, rate of rise in force, and sway in center of pressure (COP). RESULTS: Significant improvement in sit-to-stand performance was found in patients in the training group. Body weight was distributed more symmetrically in both legs, with less mediolateral sway in the COP when rising and sitting down. The mean difference in body-weight distribution between the left and right legs while subjects were rising from a chair significantly decreased, from 49.5% +/- 18.9% to 38.6% +/- 15.8% of body weight (BW) (p < .005). The rate of rise in force while rising from a chair significantly increased, from 28.3% +/- 13.5%BW/s to 53.6% +/- 20.5%BW/s (p < .001). At the 6-month follow-up, 10 of 24 patients (41.7%) in the control group had fallen, compared with only 5 of 30 patients (16.7%) in the training group (p < .05). CONCLUSIONS: Symmetrical body-weight distribution training may improve sit-to-stand performance and, consequently, decrease the number of falls by stroke patients.

Accidental Falls↗

Corneal temperature reversal after storage in Chen medium compared with Optisol GS.

PURPOSE: To compare corneal endothelial cell function by measuring corneal thickness during temperature reversal between corneas stored in two different storage media, Optisol GS and Chen Medium (CM). METHODS: Twenty paired corneas from 10 human donors were randomly assigned for storage at 4 degrees C in Optisol GS (10 corneas) or CM (10 corneas). The storage media were masked, and measurements were done in a masked fashion. After storage for 48 hours, corneal thickness was measured by ultrasonic pachymetry at 2-hour intervals for 12 hours, during which time the corneas were perfused with BSS (balanced salt solution) Plus at 37 degrees C. Scanning electron microscopy of two pairs of corneas from two donors was performed to assess ultrastructural change after 12 hours of warming. RESULTS: Corneal thickness decreased during the first 4 hours of the warming period and then increased during the 6-to 12-hour warming period. These changes in corneal thickness over time were similar for the two storage media (p = 0.212). Scanning electron microscopy showed greater amounts of endothelial cell disruption in Optisol GS-stored corneas than those stored in CM after 12 hours of warming and perfusion. CONCLUSIONS: The endothelial pump of corneas stored in CM appear to be as well-preserved as those stored in Optisol GS, although greater endothelial disruption may be present with Optisol GS by scanning electron microscopy. Further studies are required to compare the clinical effectiveness of these two media.

Aged↗

Characterization of the caspase inhibitor IDN-1965 in a model of apoptosis-associated liver injury.

Previous studies have shown that caspase inhibitors are effective at protecting against anti-Fas antibody (alpha-Fas)-mediated liver injury/lethality. The purpose of these experiments was to characterize more fully the efficacy of a broad-spectrum, irreversible caspase inhibitor, IDN-1965 (N-[(1,3-dimethylindole-2-carbonyl)valinyl]-3-amino-4-oxo-5-fluoropentanoic acid), in this model and the role of caspase inhibition in long-term protection. The ED(50) for IDN-1965 by i.p. administration, based on alanine aminotransferase activities, was 0.14 mg/kg. The caspase inhibitor was also efficacious when administered intravenously and orally (ED(50) values of 0.04 and 1.2 mg/kg, respectively). Histologically, marked reduction in Fas-induced apoptosis with IDN-1965 (1 mg/kg, i.p.) was apparent at 6 h. Also, caspase 3-like activities were decreased in a dose-dependent manner, but the inhibition of caspase activity was transient. Immunohistochemical studies demonstrated that IDN-1965 greatly reduced the activation of caspase 3. In survival studies, a single i.p. treatment of 1 mg/kg IDN-1965 or continuous i.p. infusion via osmotic pumps completely blocked lethality measured up to 7 days after alpha-Fas administration. IDN-1965 was also effective in inhibiting liver injury when administered as long as 3 h after or 1 h before alpha-Fas administration. Lastly, Western blot analysis demonstrated that processing of caspases 3, 6, and 8, as well as Bid (a protein responsible for the release of mitochondrial cytochrome C and amplification of the apoptotic cascade) was inhibited by IDN-1965. In conclusion, the broad-spectrum caspase inhibitor IDN-1965 is markedly effective at inhibiting Fas-mediated apoptosis by multiple routes of administration. The therapeutic potential of caspase inhibitors appears promising for the treatment of apoptosis-mediated liver injury based on potency and postinsult efficacy.

Alanine Transaminase↗

Heavy membrane-associated caspase 3: identification, isolation, and characterization.

Heavy membrane preparations from 697 lymphoblastoid cells contain a tightly bound caspase zymogen. This heavy membrane-bound procaspase can be efficiently liberated from membrane preparations using detergents. Alternatively, the procaspase can be rapidly processed and activated from membrane preparations by caspase-1 without detergents. The activated caspase-3 was purified using affinity chromatography and characterized by amino acid sequencing and inhibitor specificity analysis. The sequence indicates that this heavy membrane bound caspase is caspase-3. The kinetic properties and inhibitor binding specificity also show that this purified caspase is enzymologically indistinguishable from cytoplasmic or recombinant caspase-3. However, the N-termini of activated heavy membrane-bound and cytoplasmic caspase-3 are slightly different; peptide sequencing data indicate that the heavy membrane caspase-3 begins at Lys 14, whereas the cytoplasmic enzyme begins at Ser 10. Implications of this structural difference are discussed.

Amino Acid Sequence↗

An olfactory sensory map in the fly brain.

We have isolated the "complete" repertoire of genes encoding the odorant receptors in Drosophila and employ these genes to provide a molecular description of the organization of the peripheral olfactory system. The repertoire of Drosophila odorant receptors is encoded by 57 genes. Individual sensory neurons are likely to express only a single receptor gene. Neurons expressing a given gene project axons to one or two spatially invariant glomeruli in the antennal lobe. The insect brain therefore retains a two-dimensional map of receptor activation such that the quality of an odor may be encoded by different spatial patterns of activity in the antennal lobe.

Amino Acid Sequence↗

A comparison of tangent screen, goldmann, and humphrey perimetry in the detection and localization of occipital lesions.

OBJECTIVE: To compare manual kinetic perimetry with tangent screen and Goldmann techniques and automated static perimetry with the Humphrey Field Analyzer in the detection and localization of occipital lobe lesions. DESIGN: Prospective consecutive comparative case series. PARTICIPANTS: Twelve patients with well-defined occipital lobe infarcts on magnetic resonance (MR) imaging were studied. MAIN OUTCOME MEASURES: The patients were tested by tangent screen, Goldmann, and Humphrey perimetry (central 30-2 threshold program). The three visual fields were compared and correlated with MR images. RESULTS: All three perimetric techniques detected the presence of postchiasmal lesions. However, localization of lesions differed with perimetric technique. Visual fields obtained from tangent screen and Goldmann perimetry were similar and corresponded well with the location of lesions on MR images in all 12 patients. Humphrey perimetry inaccurately localized the lesion to the proximal part of the postchiasmal pathway by revealing incongruous fields in two patients, failed to detect sparing of the posterior occipital cortex or occipital pole in four patients, and estimated a larger extent of damage in one patient when compared with MR images and manual perimetry. CONCLUSIONS: All three perimetric techniques are satisfactory screening tests to detect occipital lesions. However, tangent screen and Goldmann perimetry provide information about the location and extent of lesions that is more consistent with prevailing knowledge of the effects of the lesion in the postgeniculate visual pathway.

Adult↗

Healing of autogenous intramembranous bone in the presence and absence of homologous demineralized intramembranous bone.

This study was designed to examine the osteogenecity of demineralized bone matrix (DBM) prepared from intramembranous (IM) bone and to quantitatively assess the amount of new bone formed by IM autogenous bone grafts with or without DBM(IM). Forty-two defects were created in 42 New Zealand White rabbits. Twenty-one defects were grafted with IM bone alone, and the other 21 defects were grafted with composite IM-DBM(IM). Eleven rabbits, 22 defects were used as controls, where 11 defects were left empty (passive control) and the other 11 defects were filled with rabbit skin collagen (active control). Tissues were retrieved on days 1, 2, 3, 4, 5, 6, 7, and 14 for qualitative and quantitative analysis. Cells involved in the healing of composite IM and IM-DBM(IM) bone grafts were identified. No cartilage cells were detected during the healing of either grafts. Appearance of small blood vessels into the newly formed matrix was seen on day 5 in IM bone grafts and on day 4 in composite IM-DBM(IM) bone graft. Quantitative analysis was performed by means of image analysis on 100 sections of tissues retrieved after 14 days. Approximately 204% more new bone was formed in defects grafted with composite IM-DBM(IM) than in those grafted with IM bone alone (P <.0001). No bone was formed across the defects in either active or passive controls. In conclusion, DBM(IM) significantly increases the osteogenicity of IM bone grafts.

Analysis of Variance↗