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Biomedical subjects

M L Ko

Publications and source records attributed to M L Ko.

9 recordsLinked to original sources

Patterns of retinal ganglion cell survival after brain-derived neurotrophic factor administration in hypertensive eyes of rats.

We investigated the effect of brain-derived neurotrophic factor (BDNF) on retinal ganglion cell (RGC) survival after intraocular pressure (IOP) elevation at various time intervals. In adult Wistar rats, RGCs were labeled with 5% Fluorogold. Animals with 1.8-2.5-fold increase in IOP after cauterization of three episcleral vessels, were divided into three BDNF groups and three vehicle control groups, each receiving one, two or three injections. The RGC survival percentage on RGCs of the first, second and third injections were 93.9% (n = 7), 91.3% (n = 7), 82.7% (n = 5), respectively in BDNF groups; 91.6% (n = 6), 84.1% (n = 6) and 73.5% (n = 5), respectively in vehicle controls. The second and third injections of BDNF showed statistically significant survival effects. These findings demonstrated that BDNF has partial neuroprotection on RGCs in whole retina and enhances RGC survival in moderately chronic hypertensive eyes.

Animals↗

Developmental expression of retinal cone cGMP-gated channels: evidence for rapid turnover and trophic regulation.

The cyclic GMP-gated cationic channels of vertebrate photoreceptors are essential for visual phototransduction. We have examined the developmental regulation of cGMP-gated channels in morphologically identified cones in the chick retina. Expression of cone-type cGMP-gated channel mRNA can be detected at embryonic day 6 (E6), but expression of functional channels, as accessed by patch-clamp recordings, cannot be detected until E8. Plasma membrane channels in embryonic cones have a high turnover rate because inhibition of protein synthesis or disruption of the Golgi apparatus causes an almost complete loss of functional cGMP-gated channels within 12 hr. Different subpopulations of cones begin to express functional channels at different developmental stages, but all cones express channels by E10. Expression of cGMP-gated channels in at least one cone subpopulation appears to require one or more soluble differentiation factors, which are presumably present in the normal microenvironment of the developing retina. Application of chick embryo extract (CEE), a rich source of trophic factors, causes marked stimulation of cGMP-gated channel expression in chick cones at E8, but not at E6. Inhibition of MAP kinase (Erk) signaling using PD98059, or inhibition of PI3 kinase signaling by LY294002, blocked the stimulatory effects of CEE on E8 cones. Several recombinant trophic factors were also tested, but none could mimic the stimulatory effects of CEE on channel expression. In summary, the developmental expression of cGMP-gated cationic channels in embryonic cones appears to be regulated by epigenetic factors. The ability of cones to respond to these epigenetic factors is also developmentally regulated.

Animals↗

Circadian regulation of cGMP-gated cationic channels of chick retinal cones. Erk MAP Kinase and Ca2+/calmodulin-dependent protein kinase II.

cGMP-gated channels are essential for phototransduction in the vertebrate retina. Here we show that the affinity of these channels for cGMP in chick cones is substantially higher during the subjective night than during the subjective day. This effect persists in constant environmental conditions after entrainment to 12:12 hr light-dark cycles in vitro or in ovo. Circadian modulation of ligand affinity is a posttranslational effect and is driven by rhythms in the activities of two protein kinases: Erk and Ca2+/calmodulin-dependent protein kinase II (CaMKII). Erk is maximally active during the subjective night, whereas CaMKII is maximally active during the subjective day. Acute inhibition of these signaling pathways causes phase-dependent changes in the affinity of the channels for cGMP.

Animals↗

The combined effect of brain-derived neurotrophic factor and a free radical scavenger in experimental glaucoma.

UNLABELLED: PURPOSE. Brain-derived neurotrophic factor (BDNF) had a limited effect on the survival of retinal ganglion cells (RGCs) in rats' eyes with elevated intraocular pressure (IOP). The combined treatment of BDNF and a nonspecific free radical scavenger N-tert-butyl-(2-sulfophenyal)-nitrone (S-PBN) was investigated on the RGCs in hypertensive eyes of rats. METHODS: Adult Wistar rats were separated into five groups: BDNF (0.5 microg) + S-PBN; BDNF (1. 0 microg) + S-PBN; BDNF (1.0 microg); S-PBN; and phosphate-buffered saline. Right eyes served as normal controls (n = 10). RGCs were labeled with 5% Fluoro Gold; injected into the superior colliculus. Three days after intratectal injection, the episcleral veins of the left eyes were cauterized. Intravitreal injection of BDNF was performed on days 5, 13, 21, and 29 after IOP elevation. S-PBN was injected intraperitoneally (100 mg/kg body wt) every 12 hours starting 30 minutes after cauterization. RESULTS: The survival of RGCs using BDNF treatment alone in moderately hypertensive eyes and systemic administration of S-PBN alone did not significantly rescue the RGCs. However, the combination of BDNF and S-PBN increased the survival of RGCs to 90.1%. CONCLUSIONS: Trophic factors and antioxidants have synergistic effects on rescuing RGCs from death in eyes with elevated IOP. Further studies of different combined treatment therapies may provide avenues to save RGCs from death in eyes with elevated IOP.

Animals↗

Outcome of recommendations for augmentative communication in children.

Some children with severe motor disorders have unintelligible speech, and may be recommended augmentative communication systems, such as a symbol chart or a voice output aid. The paper reports the outcome after 15-18 months for 35 children of recommendations for augmentative communication. Using structured questionnaires, parents were asked whether equipment was provided as recommended. Their perception of success in children's use of augmentative aids was recorded and related to potentially influential factors. Twenty-five symbol systems, 10 speech output devices and 11 switches were received; 18 symbol systems were used for communication and 10 were used frequently. Seven speech output devices were used for communication but only two were reported to be used frequently. Factors leading to more successful outcomes include early receipt of the aid, perceived adequate local training in the use of the aid, and children aged 6 years or more at initial assessment. The findings also suggest that referring professionals will need to be better informed about the nature and limitations of augmentative communication aids, and that improved local professional input and careful interagency planning and co-ordination are required to achieve optimal outcome.

Adolescent↗

The effects of aging on spinal neurochemistry in the rat.

The purpose of this study was to investigate how the aging process alters the basal levels of serotonin, norepinephrine, dopamine, and their respective metabolites in the spinal cord using high-performance liquid chromatography and electrochemical detection. Young, mature and aged male Fischer 344 rats (5-6, 15-16, and 25-26 months old, respectively) were used in all experiments. Dorsal and ventral halves of the cervical, thoracic, lumbar and sacral vertebral sections of the rat spinal cord were analyzed. The results indicate that as chronological age increases, local spinal levels of serotonin and norepinephrine decrease. These findings are discussed in terms of how age-related changes in the endogenous levels of the biogenic amines may alter the perception of pain in the elderly.

Aging↗

Outcome of referrals to a district immunisation advisory clinic.

We have studied referrals to and outcomes of consultation at a district immunisation advisory clinic, aiming to examine and confirm the rarity of true contraindications, the safety of immunising children with possible contraindications, and the influence on parents of counselling by well informed professionals. We examined medical records and postal questionnaires to parents, representing 30 months' work. Three hundred and fifty-eight children were referred to the clinic, 248 of whom were seen and 110 (31%) did not attend. Fourteen children who attended (6%) had a true contraindication to the vaccine(s) in question and 202 of the remaining 234 (86%) proceeded to vaccination with no adverse effect. Forty of the 110 (36%) who were referred but did not attend were vaccinated, and no adverse effects were reported, but the immunisation rate of this group was significantly lower than that seen in the clinic (chi 2 test, p < 0.001). True contraindications to childhood immunisation were rare, and children with difficult problems were safely vaccinated. The immunisation advisory clinic is effective in counselling parents who are uncertain about childhood immunisation.

Adolescent↗

What do parents know about vitamins?

Parents of 120 children attending child health clinics answered a questionnaire on their understanding of vitamins. Fifty four children (45%) were taking vitamins; 12 (22%) were given the wrong dose. Only 19 parents (35%) knew when to stop supplements and 25 (46%) did not realise overdosage was potentially harmful. Only six children (11%) were receiving professional supervision. This indicates a need to improve parental understanding and professional supervision.

Awareness↗