Long-term potentiation (LTP) at hippocampal CA3-CA1 synapses is often associated with increases in quantal size, traditionally attributed to enhanced availability or efficacy of postsynaptic glutamate receptors. However, augmented quantal size might also reflect increases in neurotransmitter concentration within the synaptic cleft since AMPA-type glutamate receptors are not generally saturated during basal transmission. Here we report evidence that peak cleft glutamate concentration ([glu]cleft) increases during LTP, as indicated by a lessening of the blocking effects of rapidly unbinding antagonists of AMPA. The efficacy of slowly equilibrating antagonists remained unchanged. The elevated [glu]cleft helps support the increased quantal amplitude of AMPA-type EPSCs (excitatory postsynaptic currents) during LTP.
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ; Glutamic Acid* ; Long-Term Potentiation ; Neurotransmitter Agents ; Receptors, Glutamate ; Synapses

Conventional views of synaptic transmission generally overlook the possibility of "postfusional- control" the regulation of the speed or completeness of transmitter release upon vesicular fusion. However, such regulation often occurs in non-neuronal cells where the dynamics of fusion-pore opening is critical for the speed of transmitter release. In case of synapses, the slower the transmitter release, the smaller the size and rate-of-rise of postsynaptic responses would be expected if postsynaptic neurotransmitter receptors were not saturated. This prediction was tested at hippocampal synapses where postsynaptic AMPA-type glutamate receptors (AMPAR) were not generally saturated. Here, we found that the small miniature excitatory postsynaptic currents (mEPSCs) showed significantly slower rise times than the large mEPSCs when the sucrose-induced mEPSCs recorded in cyclothiazide (CTZ), a blocker for AMPAR desensitization, were sorted by size. The slow rise time of the small mEPSCs might result from slow release through a non-expanding fusion pore, consistent with postfusional control of neurotransmitter release at central synapses.
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid* ; Excitatory Postsynaptic Potentials ; Neurotransmitter Agents ; Receptors, AMPA* ; Receptors, Glutamate ; Receptors, Neurotransmitter ; Synapses* ; Synaptic Transmission

BACKGROUND: Recently, a new EIA method for pancreatic amylase was introduced that was assayed by inhibition of the salivary amylase using the synergistic action of two monoclonal antibodies. We evaluated the clinical usefulness of the pancreatic amylase by using the sensitivity, the specificity and diagnostic accuracy of the receiver-operator characteristics (ROC) curve. METHODS: We divided into 3 groups: acute pancreatitis (n=26) diagnosed by ultrasonography and computed tomography, control patients (n=105), and healthy controls (n=95). Serum total amylase, pancreatic amylase, and lipase were assayed by the Hitachi 7170. The upper limit of the reference range of the total amylase, pancreatic amylase, and lipase was respectively 216 U/L, 115 U/L and 200 U/L in this hospital. RESULTS: The sensitivity of total amylase, pancreatic amylase, and lipase for the diagnosis of acute pancreatitis was 73.1%, 88.5%, and 92.3%, respectively. The specificity of total amylase, pancreatic amylase, and lipase was 70.5%, 81.9%, and 82.9%, respectively. The diagnostic accuracy, determined as the area under the curve, was 0.795 for total amylase, 0.868 for pancreatic amylase, and 0.886 for lipase. There was a significant difference between the total amylase and pancreatic amylase (P=0.045), but not a significant difference between the pancreatic amylase and lipase (P=0.613) by ROC curve. CONCLUSIONS: Pancreatic amylase had a higher sensitivity, specificity, and diagnostic accuracy than the total amylase, and showed a similar diagnostic performance as lipase. Therefore, we concluded that the pancreatic amylase was a better diagnostic tool than the total amylase in the diagnosis of acute pancreatitis.
Amylases* ; Antibodies, Monoclonal ; Diagnosis ; Humans ; Lipase ; Pancreatitis* ; Reference Values ; ROC Curve ; Sensitivity and Specificity ; Ultrasonography

BACKGROUND: The molecular events leading to the development of sporadic late-onset Alzheimer's disease (AD) have not been defined. A number of mechanism for the protective effects of non-steroidal anti-inflammatory drugs (NSAIDs) in AD have been proposed. We investigated the ibuprofen effect of global gene expression on the amyloid-beta25-35 (Abeta25-35)-stimulated human astrocytoma cell. METHODS: U373MG, a human astrocytoma cell line, was incubated with 25 microM of aggregated Abeta25-35 or aggregated Abeta25-35 plus 100 microM ibuprofen at 37degrees C for 24 hours. Cells treated with ibuprofen alone were used as the negative control. Differential gene expression analysis was carried out with the Illumina human whole genome microarray. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was also done to validate the gene expression changes. After Welch's t-test, the significant subset of outlier genes were identified by an expression change cut-off 1.5 fold, p<0.05. Kyoto Encyclopedia of Genes and Genomes database was used for cellular signaling pathway analysis. RESULTS: A total of 371 differentially expressed genes were identified from 16,692 detectable signals in Abeta25-35 peptide stimulated U373MG cells- 182 up-regulated genes with 21 biological pathways including biosynthesis of steroid, peroxisome proliferator-activated receptor signaling pathway and focal adhesion and 189 down-regulated genes with 14 biological pathways including transforming growth factor-beta signaling pathway, axon guidance and mitogen activated protein kinase signaling pathway. Ibuprofen suppressed the up-regulated expression of immunity/inflammation (especially, SERPINE1), signal pathway, metabolism and cancer-related genes. The expression of microarray data was confirmed by real-time RT-PCR. CONCLUSION: Aggregated Abeta25-35 induces expression of widespread transcriptional alterations, namely 21 functional groups 182 up-regulated genes and 14 functional groups 189 down-regulated genes in U373MG cells. Ibuprofen, a commonly used NSAID, suppressed Abeta25-35-induced increase of global changes in transcription of sets of genes especially immunity/inflammation, signal pathway, metabolism and cancer-related genes.
Alzheimer Disease ; Amyloid beta-Peptides ; Anti-Inflammatory Agents, Non-Steroidal ; Astrocytoma ; Axons ; Cell Line ; Focal Adhesions ; Gene Expression ; Genome ; Humans ; Ibuprofen ; Oligonucleotide Array Sequence Analysis ; Peptide Fragments ; Peroxisomes ; Protein Kinases ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction

Metabotropic glutamate receptors (mGluRs), classified into three groups (group I, II, III), play a critical role in modulation of synaptic transmission at central and peripheral synapses. In the present study, extracellular field potential recording techniques were used to investigate effects of mGluR agonists on excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala. The non-selective mGluR agonist t-ACPD (100 microM) produced reversible, short-term depression, but the group III mGluR agonist L-AP4 (50 microM) did not have any significant effects on amygdala synaptic transmission, suggesting that group I and/or II mGluRs are involved in the modulation by t-ACPD. The group I mGluR agonist DHPG (100 microM) produced reversible inhibition as did t-ACPD. Unexpectedly, the group II mGluR agonist LCCG-1 (10 microM) induced long-term as well as short-term depression. Thus, our data suggest that activation of group I or II mGluRs produces short-term, reversible depression of excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala. Considering the long-term effect upon activation of group II mGluRs, lack of long-term effects upon activation of group I and II mGluRs may indicate a possible cross-talk among different groups of mGluRs.
Amygdala* ; Depression ; Receptors, Metabotropic Glutamate* ; Synapses ; Synaptic Transmission*

BACKGROUND: Rotavirus is the most common cause of childhood diarrhea worldwide. Although rotavirus is also the leading cause of infant and childhood diarrhea in Korea, much remains unknown about the trends of rotavirus infection by month and geographic region in Korea. To monitor epidemiologic trends of rotavirus infection, a laboratory-based rotavirus surveillance network was established in 2002. This is the first nationwide, multicenter evaluation of rotavirus epidemiology in Korea. METHODS: The rotavirus test results were collected retrospectively from eight network laboratories, from July 1999 to June 2002. Four laboratories used latex agglutination, three used immunochromatography, and one used enzyme-linked fluorescent assay for the detection of rotavirus antigen. RESULTS: Of 10, 441 stool specimens, 2, 496 (23.9%) were positive for rotavirus. During the 3-year period, the rotavirus season began in December-January, and ended in April-May. The rotaviruspositive percentage of summer, autumn, winter, and spring was 11.5%, 10.0%, 32.8%, and 30.0%, respectively. A few hospitals revealed summer epidemics. The rotavirus positive rate in each hospital varied from 15.3% to 44.2%. A common feature of the three hospitals showing the lowest rotavirus-positive percentage (i.e. <20%) was their large size (>800 beds). The secondary care hospitals showed a higher positive proportion (27.5%) compared with tertiary care hospitals (21.1%). CONCLUSIONS: Overall, the rotavirus-positive percentage among all diarrheal specimens was similar to that of other developed countries. The results of this study showed that the autumn epidemic of the rotavirus has declined or disappeared and the peak season for rotavirus has shifted to late winter/early spring in Korea.
Agglutination ; Developed Countries ; Diarrhea ; Epidemiology ; Humans ; Immunochromatography ; Infant ; Korea ; Latex ; Republic of Korea* ; Retrospective Studies ; Rotavirus ; Rotavirus Infections* ; Seasons ; Secondary Care ; Tertiary Healthcare