[Molecular bases of color vision].
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Animals↗
Biomedical subjects
X L Yang
Publications and source records attributed to X L Yang.
[Modulation of visual information in the retina].
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Animals↗
Dark adaptation of horizontal cells in the teleost fish retina.
The dark adaptation behaviors of rod-driven and cone-driven horizontal cells were examined by analyzing their light responses recorded intracellularly in the intact, immobilized carp, and compared with that of the electroretinographic b-wave recorded simultaneously. Like the b-wave, the light responsiveness of rod horizontal cells increased gradually with time in the dark and attained a steady level at 60 min. On the other hand, cone horizontal cells initially increased in light responsiveness in the first 10 min, but thereafter decreased steadily so that the response amplitudes of these cells to bright light flashes were only 3-5 mV. The results suggest that cone horizontal cells are strongly suppressed in prolonged darkness.
Animals↗
Developmental expression of plasminogen activator inhibitor type 1 by human alveolar macrophages. Possible role in lung injury.
Urokinase activity is regulated by the specific endogenous plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2). One of these inhibitors, PAI-1, has been directly implicated in connective tissue metabolism by virtue of its ability to bind extracellular matrix proteins. Because the normal lung is relatively rich in urokinase and abnormalities in urokinase activity have been associated with fibrotic lung diseases, we have explored the possibility of local production of PAI-1 and PAI-2 in human lung. Reverse transcription and subsequent amplification by the polymerase chain reaction of total lung RNA revealed PAI-1 mRNA in each of three normal samples and in two specimens from patients with the adult respiratory distress syndrome (ARDS). In situ hybridizations of lung biopsy specimens from a patient with ARDS with cRNA probes to PAI-1 and PAI-2 indicated that alveolar macrophages express PAI-1 mRNA during the acute injury phase. Subsequent reverse transcription and PCR amplification of normal human monocyte and alveolar macrophage mRNA revealed that neither cell type expressed mRNA for urokinase inhibitors. However, after 24 h stimulation with endotoxin in vitro, monocytes were strongly positive for PAI-2 but negative for PAI-1 mRNA whereas, under the same conditions, alveolar macrophages exhibited mRNA for both PAI-1 and PAI-2. Metabolic labeling of endotoxin-stimulated alveolar macrophages with 35S-methionine followed by immunoprecipitation with PAI-1 and PAI-2 antibodies revealed that macrophages synthesized both PAI-1 and PAI-2. As judged by immunoprecipitation and functional studies, PAI-2 was found to be the major intracellular PA inhibitor whereas PAI-1 was found to predominate outside the cell. Thus, mononuclear phagocytes exhibit a developmental potential for PAI-1 expression. The release of PAI-1 by stimulated macrophages, as observed in the setting of ARDS, may be one mechanism by which these cells promote connective tissue accumulation.
Endotoxins↗
Electroretinographic b-wave merely reflects the activity of the rod system in the dark-adapted carp retina.
The electroretinogram and responses of intermediate horizontal cells (IHCs) were recorded simultaneously and studied under dark-adapted conditions in intact crucian carp, with the hope of providing an answer to the controversy whether the scotopic b-wave contains contribution from both rods and cones. Our observations indicate that the dark-adapted b-wave follows the univariance principle perfectly in that: (1) b-wave forms and shapes of response amplitude vs light intensity relationships did not depend on the stimulus wavelength; (2) response amplitudes to flashes of mixed wavelengths agreed exactly with the values predicted in accordance with the univariance principle. Furthermore, the spectral sensitivity of the b-wave matched well that of the IHC, receiving input exclusively from rods. In consequence, we conclude that the dark-adapted b-wave merely reflects the activity of the rod system, and the discrepancy between the spectral sensitivities of the b-wave and IHC response compared with the absorption spectrum of the rod photopigment may be due to the self-screening effect caused by the high optical density of porphyropsin in situ.
Animals↗
[Enhancement of antitumor activity of bleomycin A5 in mouse sarcoma 180 cells in vitro and in vivo by verapamil].
Verapamil (Ver), a calcium influx blocker, enhanced the cytotoxicity of bleomycin A5 (BLM) in cultured S-180 cells. IC50 of BLM to the cells was about 2.6 micrograms/ml when the cells were treated with BLM alone, but when the cells were treated with BLM plus Ver 1, 5, 10 micrograms/ml, the IC50 were 1/1.2, 1/5.2, 1/7.4 of the cells treated with BLM alone, respectively. In colony test, the survival fractions of the cells treated with BLM 20, 60, 100 micrograms/ml plus Ver 60 micrograms/ml were 1/7, 1/8, 1/11 of the cells treated with BLM alone, respectively. Ver enhanced the growth inhibitory actions of BLM in mice bearing S-180 sarcoma by 60% or over. The mean survival the growth inhibitory actions of BLM in mice bearing S-180 sarcoma by 60% or over. The mean survival time of the mice bearing S-180 ascites sarcoma treated with BLM plus Ver was prolonged 21% from that of the mice treated with BLM alone. The results suggest that Ver may be used clinically as an antitumor enhancer of BLM.
Animals↗
Synaptic inputs from rods and cones to horizontal cells in the tiger salamander retina.
Synaptic inputs from rods and cones to horizontal cells (HCs) were studied in the flatmounted isolated retinas of the tiger salamander. Voltage-intensity relations, spectral sensitivities and response waveforms of the rod, the cone, and the HC under dark- and light-adapted conditions were examined. HCs receive mixed inputs from rods and cones in both dark- and light-adapted retinas. The relative rod/cone input in HCs depends on the intensity of stimulus and background illumination, and it varies from HC to HC.
Ambystoma↗
Modulation of rod-cone coupling by light.
Although electrical coupling between rods and cones in the retina has been assumed to be static, it has now been shown that rod-cone coupling can be strengthened by light. Increment threshold measurements reveal that cone input to rods increases progressively as background light becomes brighter. Current injection into cones produces larger responses in adjacent rods in the presence of background light than in darkness. Weak coupling under dark-adapted conditions facilitates synaptic transmission of small rod signals, and strong coupling under light-adapted conditions enhances transmission of large cone signals.
Ambystoma↗
Functional status of the pituitary-adrenal axis during treatment of RU486 for termination of early pregnancy in combination with PGs in Chinese women.
Six pregnant women (below 49 days of amenorrhea) desiring pregnancy termination received 600 mg RU486 orally in a single dosage and 1 mg PG-05 or ONO-802 as vaginal suppository 48 h afterward. Plasma cortisol, corticosterone, aldosterone and ACTH were monitored at -0.5, 1, 2, 4, 10, 24, 48, 72 h as well as during the first follow-up visit at the 8th day. Cortisol increased during the treatment and the values returned to the pretreatment level by the first follow-up visit. The changes of corticosterone were similar to those of cortisol. ACTH was also elevated within first 2 h and returned to the basal level at 48 h. There was no notable change in aldosterone during the treatment. The results suggest that a compensation of the pituitary-adrenal function occurred during the treatment, which is probably associated with a decreased negative feedback mechanism of cortisol due to the antiglucocorticosteroid activity of RU486 at the hypothalamus level.
Abortifacient Agents↗
Effects of CNQX, APB, PDA, and kynurenate on horizontal cells of the tiger salamander retina.
Effects of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 2-amino-4-phosphonobutyrate (APB), cis-2,3-piperidine dicarboxylic acid (PDA), and kynurenate (KYN) on the depolarizing actions of glutamate and kainate on horizontal cells (HCs) were studied in the larval tiger salamander retina. APB, PDA, and KYN hyperpolarized the HCs, but they failed to block either the actions of glutamate and kainate, or the HC light responses. APB and PDA did not cause membrane polarizations in either rods or cones, suggesting that the HC hyperpolarizations were not mediated by presynaptic actions of these compounds. CNQX, the newly synthesized non-NMDA (N-Methyl-D-Aspartate) receptor antagonist, blocked the HC light responses and the action of kainate, but not that of glutamate. These results suggest that the synaptic receptors in the tiger salamander HCs are probably non-NMDA although extra-synaptic NMDA receptors may exist in these cells.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Effects of prolonged light exposure, GABA, and glycine on horizontal cell responses in tiger salamander retina.
1. The effects of prolonged light exposure, gamma-aminobutyric acid (GABA), and glycine on the horizontal cell (HC) light responses were studied in the superfused flat-mounted isolated retinas of the larval tiger salamander. 2. Under prolonged dark-adapted conditions, the time-to-peak of the HC light response was approximately 2-4 s, and after the termination of prolonged (6-8 min) light exposure, the time-to-peak became approximately 0.5-1 s. 3. This prolonged light-induced change in response rise time was not observed in either photoreceptors or bipolar cells, and thus the change in HC response rise time may occur postsynaptically in the HC membrane. 4. Application of 100 microM of GABA mimicked prolonged darkness and reversibly slowed down the HC response rise time, and application of 100 microM bicuculline mimicked prolonged light exposure and reversibly sped up the HC response rise time. 5. Glycine also slowed down the HC response rise course, but its effect was not observable until the concentration was raised to 1-3 mM. Strychnine did not exert any effect on HC responses when applied alone, but it could reverse the glycine actions. 6. The actions of glycine disappeared in the presence of bicuculline, indicating that the GABA and glycine pathways were probably not independent. Application of 5-10 mM glycine produced an increase of flow of preloaded 3H-GABA from the retina. 7. These results indicate that GABA may be the primary modulator that slows down the kinetics of the postsynaptic membrane proteins in the HCs. The extracellular concentration of GABA is probably high in prolonged darkness, and it is low after prolonged light exposure. Glycine, when applied at high dose, results in an increase of GABA release that slows down the HC response time course. 8. Prolonged darkness and light exposure appear to modulate the HC response in the time domain through GABA, and this change in HC response time course is probably responsible for shaping the bipolar cell responses and making the retinal signals more transient under light-adapted conditions.
Acclimatization↗
Effects of background illumination on the horizontal cell responses in the tiger salamander retina.
Synaptic transmission between photoreceptors and horizontal cells (HCs) was studied in the flat-mounted isolated retinas of the tiger salamander. Background illumination expedited the rise time of the HC light response, and the HC response rise time (HCRRT) reached steady state about 2 sec after the onset of the background illumination. The change in HCRRT is probably responsible for the background-induced enhancement of the HC responses to short light stimuli. The amplitude of the HC responses to 100 msec light steps in the presence of background illumination was 2-5 times larger than that measured under dark-adapted conditions. Background illumination exerted little effect on the response rise time in cones and bipolar cells, and thus it caused no significant response enhancement in those cells. The background-induced change in HCRRT correlated closely with the rod voltage but not with the HC voltage. These results suggest that the background-induced change in HCRRT is probably mediated by postsynaptic events in HCs because no significant time course change is observed in photoreceptors and bipolar cells (which share the same synapses with the HCs). A suppressive rod action on the cone inputs in HCs may be responsible for modulating the HCRRT. By shortening the HCRRT, background illumination regulates the frequency response of the photoreceptor-HC synapse and alters the capacity of spatial resolution of retinal bipolar cells.
Ambystoma↗
Melatonin enhances horizontal cell sensitivity in salamander retina.
Intracellular electrophysiological recording techniques were utilized to investigate the possible function of retinal melatonin in the larval tiger salamander. Endogenous retinal melatonin was present and appeared to bind a membrane-enriched fraction of the salamander retina, as determined by radioimmunoassay and receptor binding studies. Melatonin added through the perfusion bath to flat-mounted retinas resulted in a horizontal cell (HC) hyperpolarization of 10-20 mV. Additionally, the amplitude of HC responses to short test flashes increased in the presence of melatonin. Voltage-intensity plots revealed that application of 500 microM of melatonin caused an increase of the HC light sensitivity and this effect was reversible. These results suggest that melatonin synthesized and released during the dark period of the diurnal cycle may alter the sensitivity of second-order neurons at a time of day when photopic input is at its lowest level.
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The dynamic changes of several reproductive hormones during termination of early pregnancy by RU486 in combination with PG-05 in Chinese women.
8 pregnant women (below 49 days of amenorrhea) were administered 600 mg RU486 orally in a single dosage, and 1 mg PG-05 as a vaginal suppository 48 h afterwards. The plasma beta-hCG, progesterone, 17 beta-estradiol and PGFM (13,14-dihydro-15-keto-PGF2 alpha) were determined by RIAs throughout the treatment. In all 8 cases, beta-hCG and progesterone levels fell following the onset of bleeding, which happened in a mean time of 39 h after RU486 administration. In 7 women who experienced complete abortion, E2 dropped after 72 h and PGFM increased two-fold within 48 h. In comparison with these results of complete abortion, the concentrations of E2 in the woman experiencing incomplete abortion were much higher, while those of PGFM were much lower. The results suggest that the primary action site of RU486 is probably in the decidual tissue, because of the progesterone-antagonistic property of RU486, which in turn leads to the drop in beta-hCG, progesterone and E2. It also indicates that RU486 may facilitate the production of endogenous prostaglandins, which can be explained by the changes of decidual tissue induced by RU486.
Abortifacient Agents↗
Suppression of cone-driven responses by rods in the isolated frog retina.
The sensitivity of rod- and cone-driven responses was studied in the isolated frog retina during the period of rapid dark adaptation following a conditioning flash which bleached a negligible amount of visual pigment. Following a conditioning flash, cone-driven b-wave responses were first enhanced and then depressed. The time courses of the enhancement and subsequent depression of cone-drive responses varies greatly with the intensity and wavelength of the conditioning flash, but were identical when the conditioning flashes were matched for equal excitation of 502 nm rods. These changes in cone-driven response sensitivity were correlated with the desensitization and recovery of rods following the conditioning flash. When signal transmission from rods to second-order cells was interrupted by the addition of L-glutamate, the conditioning flash did not produce the above-described enhancement and subsequent depression of long-wavelength receptor potential responses. The suppression of cone-driven response therefore appears to be due to a synaptically mediated influence from 502 nm rods which is maximal when the rods are in the dark-adapted state, with little or no contribution from 433 nm rods, and no involvement of the pigment epithelium.
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Electrical coupling between rods and cones in the tiger salamander retina.
Electrical coupling between rods and cones was studied in the salamander (Ambystoma tigrinum) retina by measuring the light responses and spectral sensitivities of rods and cones and by measuring the voltage responses from a rod to current pulses injected into a cone. A population of 10-20% of the photoreceptors exhibited a mixed-response waveform of the rod and the cone under dark-adapted conditions, and a response waveform closely resembled that of a cone in the presence of background illumination. Lucifer yellow injection revealed that these cells are morphologically identical to rods, and thus they are named rodcs. Dark-adapted rodcs exhibited a rod-like spectral sensitivity with a peak at approximately 520 nm that shifted to a cone-like spectral sensitivity with a peak at approximately 620 nm in response to background light (Purkinje shift). The voltage response of a rodc to a -1-nA current step injected into an adjacent cone is approximately 3.6 times larger than that of a rod to the same current step. These results indicate that there is a population of rods (rodcs) in the tiger salamander retina that is strongly coupled to the cones and that these cells allow significant mixture of rod and cone signals at the photoreceptor level.
Ambystoma↗
Modulation of cone horizontal cell activity in the teleost fish retina. II. Role of interplexiform cells and dopamine in regulating light responsiveness.
Following the destruction of the terminals of the dopaminergic interplexiform cells by intraocular injections of 6-hydroxydopamine (6-OHDA), cone horizontal cells exhibited high light responsiveness in prolonged darkness and their responses to moderate and bright full-field flashes were as large as 60 mV. Furthermore, the light responsiveness of these cells in the 6-OHDA-treated retinas was not enhanced by background illumination. The application of dopamine (50 microM) by superfusion to 6-OHDA-treated retinas resulted in a decrease in light responsiveness and changes in response waveform of the cone horizontal cells. Twenty minutes following dopamine application the responses of the cone horizontal cells closely resembled the response of cells recorded in prolonged dark-adapted retinas. Dopamine caused similar changes in cone horizontal cells recorded in light-exposed retinas, but had no obvious effects on rod horizontal cells. The selective dopamine D1 receptor antagonist, Sch 23390, enhanced cone horizontal cell responsiveness when applied to prolonged dark-adapted retinas, mimicking background illumination. The light responsiveness of cone horizontal cells recorded after application of Sch 23390 was less than that for cells in retinas that had been exposed to background lights, but light responsiveness could not be further enhanced by background illumination. Another dopamine antagonist, (+)-butaclamol, was found to have effects similar to Sch 23390 on cone horizontal cells, but (-)-butaclamol, the inactive enantiomer, did not enhance the light responsiveness of these cells. The results suggest that the dopaminergic interplexiform cells play a crucial role in the regulation of cone horizontal cell responsiveness by prolonged darkness and background illumination. These cells may release dopamine tonically in the dark, which suppresses cone horizontal cell responsiveness. Background illumination may decrease dopamine release and liberate cone horizontal cells from the suppression.
Animals↗
Modulation of cone horizontal cell activity in the teleost fish retina. I. Effects of prolonged darkness and background illumination on light responsiveness.
The effects of prolonged (greater than 2 hr) darkness and background illumination on the light responsiveness of cone horizontal cells were examined in isolated, superfused white perch retinas. In retinas from fish maintained in complete darkness for more than 2 hr, cone horizontal cells had a resting membrane potential of about -18 mV, and they generated only slow, low-amplitude (3-4 mV) responses even when stimulated with bright flashes. Following the presentation of dim background light, the cone horizontal cells slowly hyperpolarized and thereafter remained at a more hyperpolarized level (about -25 mV). Concurrently, their light responses were dramatically enhanced in size, and response amplitudes to bright flashes eventually increased to about 50 mV. This was accompanied by noticeable changes in response waveforms; following light exposure, the responses became faster and showed initial on-transients. The increase in cone horizontal cell responsiveness was graded with intensity of the background light. A similar enhancement in response amplitudes of cone horizontal cells occurred after presenting bright flashes repetitively at intervals of 9 sec. This background sensitization phenomenon was observed in both L- and C-type cone horizontal cells. When light-sensitized isolated retinas were maintained in darkness for long periods (greater than 30 min), the light responsiveness of cone horizontal cells gradually decreased. The changes in membrane potential and response waveform were opposite to those that occurred when prolonged dark-adapted retinas were exposed to background lights; the cells depolarized by 5-7 mV and light-evoked responses became slower. Effects of background illumination on rod-driven horizontal cells were examined as well. Rod horizontal cells were about 2 log units more sensitive to white light than were cone horizontal cells. When recorded in prolonged dark-adapted retinas, rod horizontal cells showed large responses (approximately 50 mV), which could not be further enhanced by background illumination. Cone horizontal cell responsiveness in the carp retina was also depressed by prolonged darkness and increased by illumination in a fashion similar to that observed in the white perch retina. The change in response amplitude was only about 2-fold in carp compared with 5- to 10-fold changes observed in white perch. These results indicate that the light responsiveness of cone horizontal cells in the teleost retina is suppressed in prolonged darkness and that background lights release the cells from suppression.(ABSTRACT TRUNCATED AT 400 WORDS)
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