Search PubMed⌕ Search

Biomedical subjects

H S Shin

Publications and source records attributed to H S Shin.

At least 37 records · Page 2Linked to original sources

Development of the visual pathway is disrupted in mice with a targeted disruption of the calcium channel beta(3)-subunit gene.

Refinement of the retinal pathways to the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN) is mediated by nitric oxide (NO). Long-term depression (LTD) can also be induced in SC and LGN during the time at which these pathways are refined, and this LTD is partially dependent on NO and L-type Ca(2+) channel function. In an effort to determine whether NO-mediated pathway refinement is also mediated by Ca(2+) channel function, we have examined the refinement of the retinocollicular and retinogeniculate pathways in mice which lack the gene for the Ca(2+) channel beta(3) subunit (CCKO) and which have significantly reduced L-type Ca(2+) currents. Injections of the anterograde tracer cholera toxin subunit B/HRP were made into one eye of these knockout animals and in wild-type mice ages postnatal day (P) 13, P19, and P26. After 48 hours, mice were perfused and sections processed by using tetramethylbenzidine histochemistry. Labeling distribution in some animals was analyzed quantitatively. Obvious differences in the distribution of the ipsilateral retinocollicular pathway were observed at P15, with the pathway being more exuberant in CCKO mice. This difference was statistically significant. More subtle differences were seen at P21 and P28. Obvious differences were also seen in the contralateral retinogeniculate pathway which in CCKO mice filled most of the domain normally occupied by ipsilateral eye fibers. This difference was also statistically significant. We conclude that reduction in L-type Ca(2+) currents has an effect on axonal refinement similar to that which occurs in NO knockout mice, which supports the possibility that L-type Ca(2+) channel-dependent LTD mediates NO-dependent axonal refinement.

Aging↗

Immunohistochemical localization of eight phospholipase C isozymes in pancreatic islets of the mouse.

The possible involvement of phospholipase C (PLC) in the regulation of insulin secretion is not clearly understood and neither its isozymes expressed nor cellular localization in the pancreatic islets is known. By using specific monoclonal antibodies, we have investigated the expression and localization of eight different PLC isozymes, beta1, beta2, beta3, beta4, gamma1, gamma2, delta1, and delta2, in the pancreatic islets of adult mice. Immunohistochemical analysis carried out on paraffin embedded sections showed a distinct pattern of expression for each of the PLC isozymes. In the central part of the islets containing beta cells, a high level of beta4 and moderate levels of beta3 and gamma1 were expressed, whereas PLC-beta1 and -gamma1 were abundantly expressed in the exocrine pancreas. These results demonstrated the heterogeneity in expression of the phospholipase C isozymes in pancreatic islets. It is conceivable that these isozymes are coupled to different receptors and perform selective tasks in the regulation of insulin secretion for glucose homeostasis.

Animals↗

Effects of transdermal nicotine on attention and memory in healthy elderly non-smokers.

RATIONALE: Nicotine has been found to improve cognitive functions in patients with Alzheimer's disease, but little is known about its effects in the healthy non-smoking elderly. OBJECTIVES: This study aimed to investigate the effects of nicotine on cognitive function in healthy non-smoking or nicotine-naïve elderly subjects. METHODS: A transdermal patch containing either 5 mg nicotine or placebo was applied on the back of 63 healthy nicotine-naïve or non-smoking elderly Koreans. Cognitive functions were evaluated with the Short Blessed Test, Rey-Kim Memory Test, and digit span test of the Korean-WAIS, both before and 5.5 h after nicotine administration. The plasma level of nicotine after testing was measured using gas chromatography. RESULTS: The subjects' memory functions in trial 5 of the Rey-Kim Memory Tests improved significantly. Furthermore, the effect on memory slope was significantly correlated with the higher plasma level of nicotine. However, the other tests did not reveal any correlation to a significant degree. CONCLUSIONS: These results suggest that nicotine of lower plasma level can improve short-term verbal memory functions in non-smoking or nicotine-naïve healthy elderly people and that some effects are dependent on nicotine plasma levels.

Administration, Cutaneous↗

Group I metabotropic glutamate receptors elicit epileptiform discharges in the hippocampus through PLCbeta1 signaling.

Activation of metabotropic glutamate receptors (mGluRs) produces multiple effects in cortical neurons, resulting in the emergence of network activities including epileptiform discharges. The cellular mechanisms underlying such network responses are largely unknown. We examined the properties of group I mGluR-mediated cellular responses in CA3 neurons and attempted to determine their role in the generation of the network activities. Group I mGluR stimulation causes depolarization of hippocampal neurons. This depolarization is primarily mediated by two sets of conductance change: the opening of a voltage-dependent cationic conductance (mediating I(mGluR(V))) and the closing of a voltage-independent (background) K(+) conductance. I(mGluR(V)) was no longer elicited by group I mGluR agonists in the presence of U73122, a phospholipase C (PLC) blocker. Also, the current could not be activated in hippocampal CA3 neurons from PLCbeta1 knock-out mice. In contrast, suppression of PLC signaling did not affect the group I mGluR-mediated suppression of background K(+) conductance. Thus, the suppression of the background K(+) conductance occurred upstream to PLC activation, whereas the generation of I(mGluR(V)) occurred downstream to PLC activation. Group I mGluR agonists normally elicited rhythmic single cell and population burst responses in the CA3 neurons. In the absence of an I(mGluR(V)) response, CA3 neurons in slices prepared from PLCbeta1-/- mutant mice could no longer generate these responses. The results suggest that I(mGluR(V)) expression in CA3 hippocampal neuron is PLCbeta1-dependent and that I(mGluR(V)) plays a necessary role in the generation of rhythmic single cell bursts and synchronized epileptiform discharges in the CA3 region of the hippocampus.

Animals↗

Expression profile of nine novel genes differentially expressed in hepatitis B virus-associated hepatocellular carcinomas.

Chronic hepatitis B virus (HBV) infection is known to be one of the major causes in the development of hepatocellular carcinoma (HCC), although the biomolecular mechanism(s) involved remain unclear. To identify the cellular gene(s) involved in HBV-associated hepatocarcinogenesis, we used the mRNA differential display method and examined three paired tumor and nontumor tissues, all of which had chromosomally integrated HBV-DNA through chronic infection. Using 240 different combinations of three one-base anchored oligo-dT primers and 80 arbitrary 13-mers, genes decreased or increased in expression more than twofold between each tumor tissue and its paired nontumor tissue were identified. Twenty-nine known genes and four novel genes were differentially over-expressed in the HCC tumor tissues. In contrast, 27 known genes and five novel genes were under-expressed in those tumor tissues. The nucleotide sequences of the nine novel gene fragments were determined and their expression patterns were examined in 40 HCC samples. HA61T2, PT18, HG63T1, and HG57T1 were preferentially over-expressed in 32 cases (80%, P<0.001), 24 cases (60%), 23 cases (57.5%) and 22 cases (55%) of the 40 tumor tissues, respectively. There was an increased frequency of HG57T1 over-expression in HCC patients with HBV-positive serology and low serum alpha-feto protein (AFP) levels (P<0.05). DNT10, PT8, PT19, ENT25 and HA6T4 were under-expressed in 26 cases (65%), 23 cases (57.5%), 21 cases (53%), 20 cases (50%) and 18 cases (45%) of the 40 tumor samples, respectively. There was a strong correlation of DNT10 under-expression with high serum AFP level in HCC patients, irrespective of HBV serology (P<0.01). HA6T4 was preferentially under-expressed in HCC tumors in patients with HBV-positive serology and high serum AFP levels (P<0.05). Thus, the functional analyses of the known and novel genes identified in this study should prove valuable to further understand the mechanism(s) of hepatocarcinogenesis.

Base Sequence↗

Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca(2+) channels.

T-type Ca(2+) currents have been proposed to be involved in the genesis of spike-and-wave discharges, a sign of absence seizures, but direct evidence in vivo to support this hypothesis has been lacking. To address this question, we generated a null mutation of the alpha(1G) subunit of T-type Ca(2+) channels. The thalamocortical relay neurons of the alpha(1G)-deficient mice lacked the burst mode firing of action potentials, whereas they showed the normal pattern of tonic mode firing. The alpha(1G)-deficient thalamus was specifically resistant to the generation of spike-and-wave discharges in response to GABA(B) receptor activation. Thus, the modulation of the intrinsic firing pattern mediated by alpha(1G) T-type Ca(2+) channels plays a critical role in the genesis of absence seizures in the thalamocortical pathway.

4-Butyrolactone↗

Sensitive determination of bisphenol A in environmental water by gas chromatography with nitrogen-phosphorus detection after cyanomethylation.

A new technique is proposed for the determination of bisphenol A in environmental water. The sample preparation consists of a single-step extraction of bisphenol A from a water sample with methylene chloride and the cyanomethyl derivatization of bisphenol A. 2,2'-Biphenol is used as an internal standard. Bisphenol A and biphenol can be quantitatively converted to their corresponding cyanomethyl ethers, which are then measured by gas chromatography with nitrogen-phosphorus detection. Peak shape and quantification of bisphenol A are excellent, with linear calibration curves over a range of 0.1-100 ng/ml. The detection limit is 0.1 ng/ml in water samples. The average recovery and RSD at a concentration of 5 ng/ml are 89.3 and 4.5%, respectively. The procedure is applicable to the quantification of bisphenol A in tap water, raw water and stream water.

Benzhydryl Compounds↗

Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel.

Calcium influx through N-type calcium channels mediates synaptic transmission at numerous central synapses and transduces nociceptive information in the spinal dorsal horn. However, the precise role of N-type calcium channels in pain perception is not fully elucidated. To address this issue, we generated and analyzed knockout mice for alpha(1B,) the pore-forming subunit of the N-type calcium channel. Homozygous mutants are viable, fertile, and show normal motor coordination. In small-diameter dorsal root ganglion neurons from mutants the density of calcium channel currents is significantly reduced, which can be accounted for by the abolition of N-type currents. We performed several pain-related behavioral tests using the mutant mice. alpha(1B)-Deficient mice show reduced response to mechanical stimuli in the von Frey test and increased tail flick latency in response to radiant heat, indicating altered spinal reflexes. However, pain response in the hot plate test is normal. In the formalin paw test, the mutant mice exhibit significantly attenuated response in Phase 2, but normal pain behaviors in Phase 1. The response to visceral inflammatory pain caused by acetic acid is also reduced in alpha(1B) knockout mice. These results suggest that the alpha(1B) subunit of N-type calcium channel plays a major role in pain perception by acting at the spinal level, but not at the supraspinal level.

Animals↗

Evaluation of an electrochemical bioreactor system in the biotransformation of 6-bromo-2-tetralone to 6-bromo-2-tetralol.

Biotransformation of 6-bromo-2-tetralone (Br-beta-tetralone) to 6-bromo-2-tetralol (Br-beta-tetralol) by yeast cells of Trichosporon capitatum (ATCC 74312) and its partially purified Br-beta-tetralone reductase was evaluated in an electrochemical bioreactor. The biotransformation rates and final product formation were significantly affected by substrate concentration, biomass and electric potential. At 2 g/l of substrate, the initial reaction rate and final product were increased by 35% and 15%, respectively, with -1.5 V of electric potential compared to without electric potential. Additional substrate (2 g/l) provided by pulse feeding to the reaction mixture at different intervals resulted in 2.1 g/l Br-beta-tetralol compared to a total of 1.2 g/l without feeding. However, the increased production was not proportionate to the amount of additionally fed substrate. Increased substrate availability by the addition of 5% (v/v) ethanol resulted in the highest reaction rate and product formation, but addition of ethanol at a concentration higher than 5% decreased the reaction rate. At low biomass, the initial reaction rates were enhanced significantly when electric potential was high, but a higher biomass was necessary to obtain a similar reaction rate when electric potential was reduced. The highest initial reaction rate (59.2 mg/l per min) was achieved with a two-fold biomass concentration of 15.6 g of dry cell weight/l, substrate at 4 g/l and electric potential at -6 V. The conversion of Br-beta-tetralone to Br-beta-tetralol with partially purified Br-beta-tetralone reductase was slow in the presence of electric potential.

Biomass↗

Performance of UASB reactor treating leachate from acidogenic fermenter in the two-phase anaerobic digestion of food waste.

This study was conducted to investigate the performance of the upflow anaerobic sludge blanket (UASB) reactor treating leachate from acidogenic fermenter in the two-phase anaerobic digestion of food waste. The chemical oxygen demand (COD) removal efficiency was consistently over 96% up to the loading rates of 15.8 g COD/l d. The methane production rate increased to 5.51/l d. Of all the COD removed, 92% was converted to methane and the remaining presumably to biomass. At loading rates over 18.7 g COD/l d, the COD removal efficiency decreased due to sludge flotation and washout in the reactor, which resulted from short HRT of less than 10.6 h. The residual propionate concentration was the highest among the volatile fatty acids (VFA) in the effluent. The specific methanogenic activity (SMA) analysis showed that the VFA-degrading activity of granule was the highest for butyrate, and the lowest for propionate. Typical granules were found to be mainly composed of microcolonies of Methanosaeta. The size distribution of sludge particles indicated that partially granulated sludge could maintain the original structure of granular sludge and continue to gain size in the UASB reactor treating leachate from acidogenic fermenter.

Acids↗

Concentrations and activity ratios of uranium isotopes in the groundwater of the Okchun Belt in Korea.

Groundwater samples obtained from the Okchun Belt in Korea were separated into particulate and filtered fraction using a 0.45 microm membrane filter and concentrations and activity ratios of uranium isotopes in the fractions were determined by chemical separation and alpha-spectrometric measurements. Most of the uranium isotopes in the groundwater were found in the filtered water. Only less than 1% of the total uranium was detected in the particulate fraction. The concentrations and activity ratios of uranium isotopes in the groundwater measured in this study were variable, depending upon sampling site. Owing to a rapid material exchange between the subterranean hot waters and the rock strata, the concentrations of 238U in the groundwater in the hot spring area were found to be about four times higher than those elsewhere. Because of the alpha-particle recoil effect, the activity ratios of 234U/238U in the groundwater taken at "cold" spring sites were variable within the range 1.20 to 3.58, depending on the residence time of the groundwater. In the hot spring area, the activity ratios of 234U/238U were close to the equilibrium value (1.10 +/- 0.07) due to rapid erosion of the rock strata by the hot spring water.

Environmental Monitoring↗

The biological significance of phospholipase C beta 1 gene mutation in mouse sperm in the acrosome reaction, fertilization, and embryo development.

PURPOSE: We carried out this study to evaluate the biological significance of phospholipase C beta 1 gene mutation in mouse sperm in the acrosome reaction, fertilization, and embryo development. METHODS: Study subjects were divided into two groups according to the sperm [intact phospholipase C (PLC) beta 1 and PLC beta 1-/- C57BL/6J x CBA F1 mouse sperm] used. The positive acrosome reaction rate labeled with fluorescein isothiocyanate-Pisum sativum agglutinin, the fertilization rate, and the rate of embryos developed to the stage of morula or blastocyst in the two groups were compared. RESULTS: The mouse sperm null for the PLC beta 1 gene showed a lower acrosome reaction rate than control sperm (69.2 vs 50.9%, P < 0.05). And the fertilization rate and the rate of embryos developed to the stage of morula or blastocyst were also lower in the group using PLC beta 1-/- mouse sperm compared to the intact group (P < 0.05; 73.5 vs 51.8% and 15.7 vs 4.3%, respectively). CONCLUSIONS: Mutation of the PLC beta 1 gene in the mouse sperm reduces the acrosome reaction rate, fertilization rate, and embryo development rate, which may be the etiologic factors responsible for the low reproductive rate of PLC beta 1-/- mouse.

Acrosome Reaction↗

PLC-beta1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex.

During development of the cerebral cortex, the invasion of thalamic axons and subsequent differentiation of cortical neurons are tightly coordinated. Here we provide evidence that glutamate neurotransmission triggers a critical signaling mechanism involving the activation of phospholipase C-beta1 (PLC-beta1) by metabotropic glutamate receptors (mGluRs). Homozygous null mutation of either PLC-beta1 or mGluR5 dramatically disrupts the cytoarchitectural differentiation of 'barrels' in the mouse somatosensory cortex, despite segregation in the pattern of thalamic innervation. Furthermore, group 1 mGluR-stimulated phosphoinositide hydrolysis is dramatically reduced in PLC-beta1-/- mice during barrel development. Our data indicate that PLC-beta1 activation via mGluR5 is critical for the coordinated development of the neocortex, and that presynaptic and postsynaptic components of cortical differentiation can be genetically dissociated.

Animals↗

Deficient long-term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C beta4 mutant mice.

Long-term depression (LTD) at parallel fibre-Purkinje cell synapse of the cerebellum is thought to be a cellular substrate for motor learning. LTD requires activation of metabotropic glutamate receptor subtype 1 (mGluR1) and its downstream signalling pathways, which invariably involves phospholipase Cbetas (PLCbetas). PLCbetas consist of four isoforms (PLCbeta1-4) among which PLCbeta4 is the major isoform in most Purkinje cells in the rostral cerebellum (lobule 1 to the rostral half of lobule 6). We studied mutant mice deficient in PLCbeta4, and found that LTD was deficient in the rostral but not in the caudal cerebellum of the mutant. Basic properties of parallel fibre-Purkinje cell synapses and voltage-gated Ca2+ channel currents appeared normal. The mGluR1-mediated Ca2+ release induced by repetitive parallel fibre stimulation was absent in the rostral cerebellum of the mutant, suggesting that their LTD lesion was due to the defect in the mGluR1-mediated signalling in Purkinje cells. Importantly, the eyeblink conditioning, a simple form of discrete motor learning, was severely impaired in PLCbeta4 mutant mice. Wild-type mice developed the conditioned eyeblink response, when pairs of the conditioned stimulus (tone) and the unconditioned stimulus (periorbital shock) were repeatedly applied. In contrast, PLCbeta4 mutant mice could not learn the association between the conditioned and unconditioned stimuli, although their behavioural responses to the tone or to the periorbital shock appeared normal. These results strongly suggest that PLCbeta4 is essential for LTD in the rostral cerebellum, which may be required for the acuisition of the conditioned eyeblink response.

Animals↗

Nutrient removal processes for low strength wastewater.

For nutrient removal from low strength wastewater, biological nutrient removal (BNR) processes available at present are not efficient due to the shortage of organic carbon. By using the carbon source obtained from the degradation of return sludge, it was attempted to enhance the efficiency of denitrification and phosphorus release. Based on its degradation mechanism, the ENR (Endogenous Nitrate Respiration) process was developed and compared with the conventional A2/O (Anaerobic/Anoxic/Aerobic), MUCT (Modified University of Cape Town) processes. In the experiment, the specific phosphorus release rates of A2/O, MUCT, and ENR processes were 0.8, 2.3, and 2.6 mg PO1-P g1 MLVSS-h. As the nitrate concentration decreased below 3.0 mg NO1-N l1 due to the endogenous nitrate respiration, the effluent nitrate of the ENR process was lower than the A2/O process and the MUCT process by 25% and 10% while the phosphorus removal efficiencies increased by 15% and 6%, respectively. It was found that the ENR process was an effective and economical alternative for removing nutrient from low strength wastewater

Biodegradation, Environmental↗

Multi-step sequential batch two-phase anaerobic composting of food waste.

This study was conducted to evaluate the newly devised process, called MUlti-step Sequential batch Two-phase Anaerobic Composting (MUSTAC). The MUSTAC process consisted of several leaching beds for hydrolysis, acidification and post-treatment, and a UASB reactor for methane recovery. This process to treat food waste was developed with a high-rate anaerobic composting technique based on the rate-limiting step approach. Rumen microorganisms were inoculated to improve the low efficiency of acidogenic fermentation. Both two-phase anaerobic digestion and sequential batch operation were used to control environmental constraints in anaerobic degradation. The MUSTAC process demonstrated excellent performance as it resulted in a large reduction in volatile solids (VS) (84.7%) and high methane conversion efficiency (84.4%) at high organic loading rates (10.8 kg VS m(-3) d(-1)) in a short SRT (10 days). Methane yield was 0.27 m3 kg(-1) VS, while methane gas production rate was 2.27 m3 m(-3) d(-1). The output from the post-treatment could be used as a soil amendment, which was produced at the same acidogenic fermenter without troublesome moving. The main advantages of the MUSTAC process were simple operation and high efficiency. The MUSTAC process proved stable, reliable and effective in resource recovery as well as waste stabilization.

Animals↗

Pretreatment of whole blood for use in immunochromatographic assays for hepatitis B virus surface antigen.

Immunochromatographic assays (ICAs) are also referred to as rapid tests, since they are simple and the results can be obtained within minutes after manually loading a few drops of a sample into each sample well of the test device. However, whole blood cannot be tested with ICA kits due to the visual hindrance caused by the color of red blood cells (RBCs), unless a cell-removing device such as a filter is mounted on the kits. Thus, when testing with blood, the advantage of the ICA kit is lost because of the additional time and machines required to coagulate and separate whole blood before preparing the serum. To overcome this limitation, whole-blood samples were added to a pretreatment solution to decolor the RBCs; the resulting mixtures were then loaded into the sample wells of the test device. The pretreating solution was composed of hydrogen peroxide (H(2)O(2)) to decolor the RBCs, Sag 471 (Osi Specialties) to restrain the mixture from vigorous foaming, sodium azide (NaN(3)) to inhibit the enzyme, which generates excessive foam at the beginning of decolorization, and EDTA as a chelating agent. As a result of this pretreatment, whole blood could be used with the ICA kit without reducing its simplicity and rapidity.

Anticoagulants↗

Requirement for the L-type Ca(2+) channel alpha(1D) subunit in postnatal pancreatic beta cell generation.

Pancreatic beta cells are the source of insulin, which directly lowers blood glucose levels in the body. Our analyses of alpha(1D) gene-knockout (alpha(1D)(-/-)) mice show that the L-type calcium channel, alpha(1D), is required for proper beta cell generation in the postnatal pancreas. Knockout mice were characteristically slightly smaller than their littermates and exhibited hypoinsulinemia and glucose intolerance. However, isolated alpha(1D)(-/-) islets persisted in glucose sensing and insulin secretion, with compensatory overexpression of another L-type channel gene, alpha(1C). Histologically, newborn alpha(1D)(-/-) mice had an equivalent number of islets to wild-type mice. In contrast, adult alpha(1D)(-/-) mice showed a decrease in the number and size of islets, compared with littermate wild-type mice due to a decrease in beta cell generation. TUNEL staining showed that there was no increase in cell death in alpha(1D)(-/-) islets, and a 5-bromo-2' deoxyuridine-labeling (BrdU-labeling) assay illustrated significant reduction in the proliferation rate of beta cells in alpha(1D)(-/-) islets.

Animals↗