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Biomedical subjects

Y J Lo

Publications and source records attributed to Y J Lo.

8 recordsLinked to original sources

Interleukin 1beta-secreting cells in inflamed gingival tissue of adult periodontitis patients.

Interleukin 1beta (IL-1beta) is a cytokine with a wide range of biological activities. It is produced by various cell types including macrophages, fibroblasts, and neutrophils. The inflammatory responses mediated by IL-1beta play an important role in periodontal tissue destruction. The purposes of this study were: (1) to determine the location of IL-1beta in inflamed human gingival tissues by the immunofluorescence method; and (2) to correlate this location to the concomitant presence of macrophage or neutrophils by immunohistochemistry. Five patients with moderate to advanced adult periodontitis receiving periodontal phase I therapy were included in this study. One month after phase I therapy, 15 sites with a probing pocket depth >/=5 mm and gingivitis index >/=1 were arranged for modified Widman flap operation. Another three sites with a probing pocket depth </=3 mm and gingivitis index=0 from two gingival healthy subjects who received crown-lengthening operation were also chosen as a control group. After clinical parameter recording, a biopsy of gingival tissues from all sites was obtained during the operation. The gingival specimens were frozen immediately for further immunofluorescent examination of IL-1beta and immunocytochemical localization of macrophages and neutrophils. The macrophages were found to be widely distributed in inflamed gingival connective tissue and near-by pocket wall tissue. The neutrophils were aggregated in pocket wall and were sparsely seen in connective tissue. IL-1beta immunofluorescent reaction was detected with high intensity in gingival connective tissue especially at the subepithelial region. IL-1beta immunofluorescence with low intensity was only occasionally seen in pocket wall tissue. There was a strong association between the presence of macrophages and IL-1beta expression. Similarly, there was a positive association between neutrophils and IL-1beta immunofluorecence. These results suggested that large amounts of IL-1beta are present in inflamed gingival tissues, and that both macrophages and neutrophils are predominate in IL-1beta production in inflamed gingival tissues.

Adult↗

Modulation of calcium by inhibitory systems in the developing auditory midbrain.

Inhibitory synaptic transmission is of fundamental importance during the maturation of central auditory circuits, and their subsequent ability to process acoustic information. The present study investigated the manner in which inhibitory transmission regulates intracellular free calcium levels in the gerbil inferior colliculus using a brain slice preparation. Inhibitory and excitatory postsynaptic potentials were evoked by electrical stimulation of the ascending afferents at the level of the dorsal nucleus of the lateral lemniscus. Pharmacologically isolated inhibitory synaptic potentials were able to attenuate a calcium rise in collicular neurons that was generated by depolarizing current injection. In addition, GABA(A) and glycine receptor antagonists typically led to an increase of calcium in collicular neurons during electrical stimulation of the ascending afferent pathway at the level of the dorsal nucleus of the lateral lemniscus. Bath application of GABA or muscimol, a GABA(A) receptor agonist, evoked a brief hyperpolarization followed by a long-lasting depolarization in inferior colliculus neurons. This treatment also induced a transient calcium increase that correlated with the membrane depolarization phase. Baclofen, a GABA(B) receptor agonist, had no effect on either membrane potential or calcium levels. Ratiometric measures indicated that the muscimol-evoked rise in calcium was approximately 150 nM above basal levels. The muscimol-evoked responses were completely antagonized by bicuculline and attenuated by picrotoxin. Together, these results suggest that inhibitory synaptic transmission participates in the regulation of postsynaptic calcium during the developmental period. Inhibitory transmission may attenuate a calcium influx that is evoked by excitatory synapses, but it can also produce a modest influx of calcium when activated alone. These mechanisms may help to explain the influence of inhibitory transmission on the development of postsynaptic properties.

2-Amino-5-phosphonovalerate↗

Xanthine oxidase inhibitors from the leaves of Alsophila spinulosa (Hook) Tryon.

Diploptene(1), beta-sitosterol(2), a mixture of 6'-O-(E-P-coumaroyl)-alpha-glucopyranose and 6'-O-(E-P-coumaroyl)-beta-glucopyranose(3), a mixture of 6'-O-(E-P-caffeoyl)-alpha-glucopyranose and 6'-O-(E-P-caffeoyl)-beta-glucopyranose(4), caffeic acid(5) and astragalin(6) were isolated from an ethanolic extract of the leaves of Alsophila spinulosa Hook Tryon (Cyatheaceae). The plant has been used in folk medicine for hepatitis, gout, rheumatism, and tumor and these compounds were tested for their inhibitory effect on xanthine oxidase. Caffeic acid was the most potent constituent (IC50 = 39.21 microM; Ki = 28.2 microM) and was an uncompetitive inhibitor of the enzyme with respect to the substrate xanthine.

Magnetic Resonance Spectroscopy↗

Heterosynaptic suppression of developing neuromuscular synapses in culture.

Activity-dependent competition between two spinal neurons coinnervating an embryonic myocyte was studied in Xenopus cell culture. We have characterized in detail the phenomenon of heterosynaptic suppression by which tetanic stimulation of one neuron results in functional suppression of the synapse made by the untetanized neuron (Lo and Poo, 1991). Fluorescence labeling of the neurons using two different fluorophores revealed that the coinnervating nerve terminals on the spherical myocyte were in close proximity. Heterosynaptic suppression could be induced when the postsynaptic cell was held under either current-clamp or voltage-clamp conditions during the tetanic stimulation. This finding, together with the observation that repetitive postsynaptic depolarization of the myocyte by direct current injection was much less effective in inducing synaptic depression, suggests that postsynaptic ACh receptor activation plays a dominant role in the induction of heterosynaptic suppression. The heterosynaptic suppression appears to be mediated by a rise of Ca2+ levels in the postsynaptic cell, since it was not observed when the cytosolic Ca2+ concentration of the myocyte was buffered at a low level with intracellular loading of a Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA). The dependence of heterosynaptic suppression on the pattern of tetanic stimulation was also studied. At a stimulation frequency of 2 Hz, detectable heterosynaptic suppression could be induced after 20 repetitive stimuli were applied to one of the presynaptic neurons and the suppression was more effective with increasing number of stimuli. Over the range of 0.5-5 Hz, the extent of suppression was independent of the frequency of tetanic stimulation and, in some cells, detectable suppression could be induced at a frequency as low as 0.05 Hz. Except for a few cases, heterosynaptic suppression was found to last for as long as the recording was made after tetanus (up to 1 hr). The fact that the mean amplitude of spontaneous synaptic currents remained the same before and after the suppression while the evoked synaptic currents exhibited higher fluctuation after suppression suggests that the observed synaptic suppression involves a reduction of evoked ACh release from the nerve terminal, although postsynaptic changes have not been excluded. Finally we found that spontaneous synaptic activity may also contribute in part to the synaptic competition between coinnervating nerve terminals. Taken together, these findings provide a quantitative basis for further understanding of activity-dependent competition between developing neuromuscular synapses.

Action Potentials↗

Depression of developing neuromuscular synapses induced by repetitive postsynaptic depolarizations.

Effect of postsynaptic activity on the synaptic efficacy was studied in Xenopus nerve-muscle cultures. Repetitive postsynaptic depolarizations induced by injection of current pulses into singly innervated myocytes resulted in significant reduction in the frequency of spontaneous synaptic currents and the amplitude of nerve-evoked synaptic currents at the majority of synapses that showed immature synaptic properties. Repetitive hyperpolarizations and steady depolarizations of similar duration were without effect. The depolarization-induced synaptic depression appeared to result predominantly from a reduced ACh secretion from the presynaptic nerve terminal. Buffering the myocyte cytosolic Ca2+ at a low level with intracellular loading of a Ca2+ buffer, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA), significantly reduced the effect of the depolarizations. Thus postsynaptic electrical activity can regulate the synaptic efficacy of the developing neuromuscular synapases and the regulation may be mediated by retrograde transsynaptic interactions.

Action Potentials↗

Activity-dependent synaptic competition in vitro: heterosynaptic suppression of developing synapses.

The development and stability of synaptic connections in the nervous system are influenced by the pattern of electrical activity and the competitive interaction between the adjacent nerve terminals. To investigate this influence, a culture system of nerve and muscle cells has been developed in which a single embryonic muscle cell is coinnervated by two spinal neurons. The effect of electrical activity on the synaptic efficacy was examined after repetitive electrical stimulation was applied to one or both neurons. Brief tetanic stimulation of one neuron resulted in immediate functional suppression of the synapse made by the unstimulated neuron innervating the same muscle cell. This heterosynaptic suppression was largely absent when the tetanic stimulation was applied concurrently to both neurons. This result demonstrates that activity-dependent synaptic competition can be studied in vitro at a cellular level.

Animals↗

Repetitive impulse activity potentiates spontaneous acetylcholine secretion at developing neuromuscular synapses.

The effects of presynaptic impulse activity on the transmitter secretion at developing neuromuscular junctions were examined in Xenopus nerve-muscle cultures. Repetitive suprathreshold stimulation of the presynaptic neuron results in marked potentiation of spontaneous synaptic activity, as shown by whole-cell voltage-clamp recording of synaptic currents in the postsynaptic muscle cell. Our results are consistent with the notion that synaptic efficacy of the developing synapse is potentiated by the presence of electrical activity. Such activity-dependent synaptic modulation enables the early neuronal activity to play a regulatory role during the maturation of synaptic connections.

Acetylcholine↗