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Biomedical subjects

K L Chow

Publications and source records attributed to K L Chow.

At least 37 records · Page 2Linked to original sources

A combination of closely associated positive and negative cis-acting promoter elements regulates transcription of the skeletal alpha-actin gene.

The chicken skeletal alpha-actin gene promoter region provides at least a 75-fold-greater transcriptional activity in muscle cells than in fibroblasts. The cis-acting sequences required for cell type-restricted expression within this 200-base-pair (bp) region were elucidated by chloramphenicol acetyltransferase assays of site-directed Bg/II linker-scanning mutations transiently transfected into primary cultures. Four positive cis-acting elements were identified and are required for efficient transcriptional activity in myogenic cells. These elements, conserved across vertebrate evolution, include the ATAAAA box (-24 bp), paired CCAAT-box-associated repeats (CBARs; at -83 bp and -127 bp), and the upstream T+A-rich regulatory sequence (at -176 bp). Basal transcriptional activity in fibroblasts was not as dependent on the upstream CBAR or regions of the upstream T+A-rich regulatory sequence. Transfection experiments provided evidence that positive regulatory factors required for alpha-actin expression in fibroblasts are limiting. In addition, negative cis-acting elements were detected and found closely associated with the G+C-rich sequences that surround the paired CBARs. Negative elements may have a role in restricting developmentally timed expression in myoblasts and appear to inhibit promoter activity in nonmyogenic cells. Cell type-specific expression of the skeletal alpha-actin gene promoter is regulated by combinatorial and possibly competitive interactions between multiple positive and negative cis-acting elements.

Actins↗

Postnatal development of the ipsilaterally projecting retinal ganglion cells in normal rats and rats with neonatal lesions.

The postnatal development of normal and anomalous uncrossed retinofugal projections in albino rats was studied using horseradish peroxidase and lectin-conjugated horseradish peroxidase as retrograde neuronal tracers. In normal rats, the number of ipsilaterally projecting retinal ganglion cells (IPRGCs) decreased continuously from more than 3000 cells on the day of birth (day 0) to slightly more than 1000 on postnatal day 5. In contrast, the number of IPRGCs in rats which received either unilateral eye enucleation or thalamectomy at birth increased abruptly to more than 4000 after 24 h on postnatal day 1, thereafter the number decreased rapidly reaching an adult level of slightly more than 2000 on postnatal day 5. The overall pattern of changes of the number, density and distribution of the IPRGCs was similar in rats which received eye enucleation or thalamectomy, although minor differences regarding the number of cells labelled in the temporal and nasal parts of retinas in rats with different lesions were detected. These findings imply that a neonatal lesion such as monocular enucleation or unilateral thalamectomy may not only result in retention of normally transient IPRGCs but also cause an increased number of IPRGCs by misrouting, rerouting or collateral sprouting of optic axons at the optic chiasma that could significantly affect the developing optic pathway. Furthermore, the differential effects of the two types of neonatal lesions upon the IPRGCs provide further evidence to previous findings that different mechanisms might be involved in generating the anomalously enlarged uncrossed retinofugal projections in rodents.

Aging↗

The origin and terminal arbors of individual uncrossed retinogeniculate fibers in rabbits.

The distribution and morphology of individual uncrossed retinogeniculate fibers in both normal and monocularly enucleated adult Dutch-belted rabbits were studied using horseradish peroxidase and wheat germ agglutinin conjugated to horseradish peroxidase as neuronal markers. The results showed that the uncrossed retinogeniculate fibers were distributed almost entirely in the ipsilateral segment of the dorsal nucleus of the lateral geniculate body, and the extent of terminal distribution of the fibers observed in rabbits with one eye enucleated during the young adult stage was essentially the same as that in the normal rabbit. Most of the uncrossed retinogeniculate fibers appeared to arise as collateral branches of optic tract fibers which were apparently destined for the pretectum or the superior colliculus. The uncrossed retinogeniculate fibers labeled by the wheat germ agglutinin conjugated to horseradish peroxidase passed through the dorsal nucleus of the lateral geniculate body without any branching until they reached the ipsilateral segment. There they could be divided into several morphological types although the possibility that they may represent different classes of a continuum cannot be ruled out.

Animals↗

Occurrence of multiple antibiotic resistance and R-plasmids in gram-negative bacteria isolated from faecally contaminated fresh-water streams in Hong Kong.

The bacterial populations of six freshwater streams in populated areas of the Hong Kong New Territories were studied. There is considerable faecal contamination of these streams, with coliform counts as high as 10(5) c.f.u./ml and the contaminating organisms show a high prevalence of antibiotic resistance and multiple resistance. With direct plating of water samples onto antibiotic-containing media, an average of 49% of the gram-negative bacteria were ampicillin-resistant, 3% chloramphenicol-resistant and 1% gentamicin-resistant. At individual sites resistance to these drugs was as high as 98%, 8% and 3% respectively. More than 70% of strains were resistant to two or more antibiotics, 29% to five or more and 2% to eight or more. A total of 98 patterns of antibiotic resistance were detected with no one pattern predominating. Twenty-eight gram-negative bacterial species were identified as stream contaminants. Escherichia coli was the commonest bacterial species isolated and other frequent isolates were Enterobacter sp., Klebsiella sp. and Citrobacter sp., but no enteric pathogens were detected. The greatest prevalence of resistance and multiple resistance was associated with the heaviest contamination by E. coli. Analysis of selected stream isolates revealed multiple plasmid bands arranged in many different patterns, but multiple antibiotic resistances were shown to be commonly mediated by single transferable plasmids. Faecally-contaminated freshwater streams in Hong Kong may be reservoirs of antibiotic resistance plasmids for clinically-important bacteria.

Animals↗

The ipsilateral retinocollicular projection in the rabbit: an autoradiographic study of postnatal development and effects of unilateral enucleation.

The postnatal development of the ipsilateral retinocollicular projection in the rabbit and the effects of unilateral enucleation (performed on the day of birth, day 0) on that development were studied by using the anterograde axonal transport of tritiated proline injected intraocularly. Material from 1-, 6-, and 10-day-old (i.e., at days 1, 6, and 10) and adult animals was examined. On day 1, autoradiographically labelled optic fibers from the ipsilateral eye formed distinct patches and bands within the superior colliculus (SC), which were restricted primarily to the lateral one-half and anterior one-third to one-half of the nucleus. At subsequent ages no major changes in the location of this projection were found for normal animals or animals enucleated on day 0 (0-DE animals). From dorsal-view reconstructions, the pattern of the ipsilateral projection appeared wedge-shaped with a broad base aligned with the lateral SC border for all normal and 0-DE animals at the various postnatal ages examined. In normal animals the surface area of this projection increased with age and maintained a constant proportion of the increasing surface area of the total SC. In 0-DE animals the surface area of the projection initially increased more rapidly than in normal animals. Thus, by day 6 the area was already within the normal adult range but did not exceed this range at later postnatal ages. The only obvious difference in the appearance of the ipsilateral retinocollicular projection between normal and 0-DE animals at corresponding ages was an enhanced radial distribution of the projection across laminae in the 0-DE animals. Taken together these findings suggest that, in the rabbit, once topographically appropriate connections are established between the SC and the ipsilateral retinal projection, they are maintained regardless of substantial postnatal growth of the SC and removal of the contralateral retinal projection to the SC.

Age Factors↗

Effects of bicuculline-induced epileptiform activity on development of receptive field properties in striate cortex and lateral geniculate nucleus of the rabbit.

Studies have shown that normal development of receptive field properties in striate cortex and lateral geniculate nucleus (LGN) of the rabbit is severely altered in the presence of penicillin-induced disruption of cortical neuronal activity. We wished to replicate these studies using a different convulsant drug in order to rule out possible effects due to the penicillin drug itself. Aqueous bicuculline was injected twice daily into a cannula implanted over the monocular region of one striate cortex. Drug administration was initiated on postnatal day 8-9 and was discontinued either on postnatal day 19-24 or on postnatal day 24-30 for studies of the LGN and striate cortex, respectively. Coincidental with the bicuculline injections, control solutions were similarly applied to the monocular region of the contralateral striate cortex. Single-unit recordings made from LGN ipsilateral to bicuculline-treated cortex revealed normal percentages of receptive field types. However, in single-unit recordings made from bicuculline-treated striate cortex, an abnormal percentage distribution of receptive field types was found. In such cortex there was an unusually high proportion of no-response type cells and a substantially reduced proportion of oriented type cells. These developmental abnormalities are virtually the same as those found in the striate cortex of similarly reared animals treated with penicillin. Our present results lend support to our previous conclusion that in the rabbit, disruption of orderly neuronal activity in the geniculostriate system has a detrimental effect on the development of receptive fields in this system.

Animals↗

Characterization of penicillin- and bicuculline-induced epileptiform discharges during development of striate cortex in rabbits.

A comparison was made between penicillin- and bicuculline-induced epileptiform activity. Aqueous solutions of either penicillin or bicuculline were applied to striate cortex of rabbit pups, and the electroencephalogram was monitored. Applications were made twice daily for 14 consecutive days beginning on postnatal day 8-9. During this time period, interictal spikes generated by bicuculline and penicillin displayed similar properties in most respects. However, the morphology of spikes induced by each convulsant was different.

Animals↗

Movement discrimination in the rabbit.

In a two-choice discrimination box, rabbits were trained to discriminate vertical vs horizontal striations. After criterion was reached, the same striations were presented again, but now the patterns moved sinusoidally. All animals immediately transferred to moving patterns. After that, it was attempted to train the animals to discriminate between moving vs non-moving vertical striations. Even after prolonged training, none of the animals learned this discrimination task.

Animals↗

Functional influences of the visuocortical projection on superior colliculus neurons in the rabbit.

The effects of electrical stimulation of the visual cortex on superior colliculus neurons were investigated in adult Dutch-belted rabbits. Single units were recorded in the superior colliculus and classified as to receptive field type. Stimulation of the ipsilateral visual cortex activated 29% of the recorded superior colliculus units. No units were driven by stimulation of the contralateral visual cortex. Comparison of the relative proportional distributions of cortically driven and not driven cells having various receptive field types revealed an over-representation of driven motion type cells. The excitatory influence of the visuocortical projection to the superior colliculus in the rabbit shows a preference for neurons responsive to moving visual stimuli.

Animals↗

Velocity-tuning of motion-sensitive and direction-selective cells in the rabbit striate cortex.

The receptive field characteristics of 268 striate cortical cells were classified in 10 Dutch-belted rabbits. From the 66 motion-sensitive and direction-selective units encountered, quantitative data describing the responses of 41 motion-sensitive, and 10 direction-selective cells to moving gratings were obtained. The results showed that all cells responded with increased spike discharges to increased velocities of the moving gratings up to a maximum, then they became less responsive to further increase of the velocities. The patterns of the response curves varied from cell to cell. When the 51 cells were taken as a whole, there were more cells responding to the velocities of 10-30 deg/sec than to higher or lower velocities. The total range over which these cells responded was 0.1-300 deg/sec. The preferred velocities for individual cells ranged from 1.5 to 150 deg/sec, showing a moderate concentration at the 6-40 deg/sec region. The extent of the effective velocities for individual cells formed a continuous distribution. No segregation into groups was seen in either of the two cell types studied or in all cells taken as a group. These data were compared with those reported for the rabbit retinal ganglion cells and the cells in the nucleus of the optic tract, as well as the cells in the cat visual system.

Animals↗

Visuocortical epileptiform discharges in rabbits: differential effects on neuronal development in the lateral geniculate nucleus and superior colliculus.

We have studied the effects of interictal epileptiform discharges originating from the striate cortex on the development of the receptive field characteristics of neurons in the lateral geniculate nucleus (LGNd) and superior colliculus (SC) in neonatal rabbits. The paroxysmal discharges were generated by twice-daily injections of penicillin into an implanted cannula. Control injections of penicillin + penicillinase were given to the other striate cortex of the same animal. Similar experimental procedures were used to study the effect of such projected discharges on the LGNd neurons in adult rabbit. The results of the first experiment show that cortical epileptiform discharges, initiated in neonatal rabbits 7--9 days of age and continuing to 20--25 days of age, retard the normal development of LGNd cells. There was an abnormal increase of indefinite cells, cells failing to respond to any light stimulation, and a concurrent decrease of cells with concentric cells was still present in adult rabbits which had interictal discharges in the striate cortex limited to the period of 7--9 days to 21--25 days of age. The fourth experiment shows that the interictal discharges in neonatal rabbits do not affect the normal receptive field development of neurons in the SC. The present results demonstrate that asymptomatic interictal epileptiform discharges, produced without focal structural damages in immature brain, can affect the development of neuronal connectivity. These results may have some clinical implications in relation to our understanding about the learning and developmental disabilities exhibited in children who had episodic seizure discharges.

Aging↗

Anomalous uncrossed retinal projections fail to activate superior colliculus neurons in rabbits unilaterally enucleated by fetal surgery.

Previous studies have shown that unilateral enucleation of rabbit pups produces an aberrant uncrossed retinotectal projection. These fibers failed to drive collicular units when stimulated with either light or electric shock. The present study attempts to assess the possibility that enucleation at earlier stages of development would lead to a greater degree of morphological and physiological reorganization in the uncrossed retinotectal projection. Rabbit fetuses were unilaterally enucleated at day 20 or 25 of gestation. Birth is at day 31. After 3 months, the degree of reorganization of the uncrossed retinotectal projection was assessed using the following techniques: (1) autoradiographic demonstration of the projection from the remaining eye, (2) electrophysiological recording of collicular unit activity, and (3) a combination of these methods. Autoradiographic data indicated a much greater expansion of the anomalous uncrossed projection in fetally enucleated animals than in those enucleated at birth. Labelled terminals were found to occupy more than the anterior third of the ipsilateral colliculus and were distributed to the entire depth of the stratum griseum superficiale and stratum opticum. Electrode penetrations within the boundaries of the expanded projection failed to locate collicular units which could be driven by either light stimulation of the eye or electric shock of the optic nerve. Only a few cells encountered in the lateral border area, receiving the normal uncrossed retinal projection, could be driven by light stimulation. These negative findings are in contrast to the data reported for the rat and hamster where anomalous retinal projections are capable of forming functional connections. Further comparative studies of reorganization are needed.

Animals↗

Callosal projections of the striate cortex in the neonatal rabbit.

Callosal fiber projections of the striate cortex were studied in newborn rabbits using the methods of 1) retrograde transport of horseradish peroxidase (HRP) and 2) orthograde transport of tritiated leucine. Data collected from 6-8 day old animals revealed not only the existence of adult-like commissural fibers in the lateral striate cortex bordering the occipital area, but also an aberrant callosal projection from the medial striate cortex, an area not known to have any commissural fibers in the adult brain of those mammalian species studied.

Afferent Pathways↗

Development of receptive field properties in the visual cortex of rabbits subjected to early epileptiform cortical discharges.

We examined the effects of early epileptiform activity on development of visuocortical receptive fields in the rabbit. Aqueous penicillin was injected twice a day into a cannula implanted over the monocular area of one visual cortex. Drug administration was begun on postnatal day 8-9 and continued until postnatal day 24-30. Concomitant with the penicillin injections a mixture of penicillin and penicillinase was similarly applied to the monocular area of the contralateral control cortex. Interictal discharges were routinely observed only from the penicillin-treated or epileptic cortex. Single-unit recordings made on postnatal day 25-31 revealed that in the neuronal population adjacent to the cortical penicillin focus percentages of receptive field types were severely altered relative to control cortex percentages. Epileptic cortex showed an abnormally high percentage of no response type cells together with an abnormally low percentage of complex and oriented-directional type cells. These abnormalities were greater closer to the penicillin focus than further from it. Epileptic visual cortex receptive field percentages are compared with those for the neonatal rabbit and the rabbit subjected to early monocular deprivation. One interpretation of our results is that development of complex and oriented-directional type cells is impeded by epileptogenic disruption of organized geniculostriate activity.

Aging↗

Effects of progressively longer durations of monocular deprivation on development of visuocortical receptive fields in the rabbit.

Three groups of rabbits were reared with monocular eyelid suture. Percentages of cells with various receptive field types were determined by recording in the deprived visual cortex of animals 30-35 days, 46-55 days, and 20-36 months old. These results, together with previously published data from two other groups of monocularly deprived rabbits, are described relative to normative data for 9-10-day-old and adult rabbits. During the first postnatal year cells in the deprived visual cortex acquire normal adult proportions of receptive field types, but do so over a longer course than that which is characteristic of cells in non-deprived visual cortex. With continued deprivation for 2-3 years there is a subsequent loss of oriented type cells and a corresponding increase in non-responsive cells.

Animals↗

Receptive field development in the dorsal lateral geniculate nucleus in rabbits subjected to monocular eyelid suture.

Receptive field properties of cells in the dorsal lateral geniculate nucleus (LGNd) were examined in 3 groups of rabbits, each subjected to monocular visual deprivation by lid suture at differing age periods. Monocular deprivation occurring from 6--8 to 20--25 days of age affected the normal development of LGNd receptive fields. A significant proportion of the cells in the deprived LGNd were either unresponsive to visual stimulation or had vague, indefinite receptive fields. Significantly fewer cells with uniform fields were found in the deprived LGNd than in the control. Percentages of concentric, motion and directional cells did not differ between the deprived and control LGNd. The diameters of receptive fields for concentric cells with sustained response properties, however, were smaller in the deprived than in the control LGNd. When deprivation was continued to 87--121 days of age, the percentage of uniform, indefinite and non-responsive cells found in the deprived LGNd approached more normal levels. Percentages of concentric, motion and directional cells were also normal. Monocular deprivation commencing at 21--22 days of age also had disruptive effects on LGNd receptive field organization, as reflected in the lower percentage of uniform and increased percentages of indefinite and non-responsive cells. These deficits, however, were not as severe as those seen in the animals deprived at an early age. A fourth group of adult rabbits subjected to monocular lid suture showed no such detrimental deficits in receptive field organization. These results demonstrated that visual deprivation affects the predominantly monocular LGNd of the rabbit, and that a critical period exists for such effects.

Age Factors↗