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Biomedical subjects

Young K Cho

Publications and source records attributed to Young K Cho.

13 recordsLinked to original sources

Efferent projection from the bed nucleus of the stria terminalis suppresses activity of taste-responsive neurons in the hamster parabrachial nuclei.

Although the reciprocal projections between the bed nucleus of the stria terminalis (BNST) and the gustatory parabrachial nuclei (PbN) have been demonstrated neuroanatomically, there is no direct evidence showing that the projections from the PbN to the BNST carry taste information or that descending inputs from the BNST to the PbN modulate the activity of PbN gustatory neurons. A recent electrophysiological study has demonstrated that the BNST exerts modulatory influence on taste neurons in the nucleus of the solitary tract (NST), suggesting that the BNST may also modulate the activity of taste neurons in the PbN. In the present study, we recorded from 117 taste-responsive neurons in the PbN and examined their responsiveness to electrical stimulation of the BNST bilaterally. Thirteen neurons (11.1%) were antidromically invaded from the BNST, mostly from the ipsilateral side (12 cells), indicating that a subset of taste neurons in the PbN project their axons to the BNST. The BNST stimulation induced orthodromic responses on most of the PbN neurons: 115 out of 117 (98.3%), including all BNST projection units. This descending modulation on the PbN gustatory neurons was exclusively inhibitory. We also confirmed that activation of this efferent inhibitory projection from the BNST reduces taste responses of PbN neurons in all units tested. The BNST is part of the neural circuits that involve stress-associated feeding behavior. It is also known that brain stem gustatory nuclei, including the PbN, are associated with feeding behavior. Therefore, this neural substrate may be important in the stress-elicited alteration in ingestive behavior.

Action Potentials↗

High frequency of grossly deleted nef genes in HIV-1 infected long-term slow progressors treated with Korean red ginseng.

To investigate the association between Korean red ginseng (KRG) intake in HIV-1 infected patients and the occurrence of grossly deleted nef genes (gDeltanef), we characterized nef genes in 10 long-term slow progressors (LTSP) infected with HIV-1 subtype B and 34 control patients. LTSP was defined by the annual decrease in CD4 T cells being less than 20/microl over 10 years in the absence of antiretroviral therapy. They were treated with KRG for a prolonged period. Nef genes were amplified from peripheral blood mononuclear cells (PBMC) using nested PCR and the products were sequenced directly. It was observed that the patients CD4 T cell counts decreased from 444 +/- 207/microl to 294 +/- 177/microl over 136 +/- 23 months of KRG intake. This corresponds to an annual decrease in the level of CD4 T cells of 13.3/microl. A total of 479 nef genes were amplified from 137 PBMC samples. Nine out of the 10 patients, 47 (34.3%) out of the 137 samples, and 90 out of the 479 genes revealed gDeltanef. The deletion extended outside the nef gene in 25 gDeltanef obtained from 6 patients. The proportion of samples with gDeltanef (34.3%) was significantly higher than 4.8% in control patients (P < 0.001). In addition, it significantly increased as the duration of KRG intake prolongs (P < 0.01). These data suggest that the occurrence of gDeltanef might be associated with long-term intake of KRG.

Adult↗

Full sequence of HIV type 1 Korean subtype B in an AIDS case with atypical seroconversion: TAAAA at TATA box.

A patient who presented with late stage HIV-associated diseases could not be diagnosed by commercial ELISA tests and a Western blot. However, we could amplify proviral DNA of HIV-1. We found a novel GPGGMI motif in the V3 loop, a novel insertion of a proline in the C3 region, and persistent deletion of two amino acids in the vif gene. The patient had been treated with HAART after diagnosis. Forty months after the first amplification of HIV-1 DNA, anti-HIV-1 antibody was confirmed by ELISA and Western blot and, thus, we amplified and sequenced HIV-1 full sequences. Interestingly, the sequence at the TATAA box was TAAAA, although full sequences were not CRF01_AE. The major differences in the level of the HIV-1 gene between the seronegative and seropositive states were changes at the glycosylation site (NXT) next to the inserted proline and many resistance mutations including M184V to antiretroviral drugs occurred. This is the first report on HIV-1 full sequences isolated from seronegative AIDS patients infected with subtype B in Korea.

Acquired Immunodeficiency Syndrome↗

Modulation of parabrachial taste neurons by electrical and chemical stimulation of the lateral hypothalamus and amygdala.

The lateral hypothalamus (LH) and the central nucleus of the amygdala (CeA) exert an influence on ingestive behavior and are reciprocally connected to gustatory and viscerosensory areas, including the nucleus of the solitary tract (NST) and the parabrachial nuclei (PbN). We investigated the effects of LH and CeA stimulation on the activity of 101 taste-responsive neurons in the hamster PbN. Eighty three of these neurons were antidromically activated by stimulation of these sites; 57 were antidromically driven by both. Of these 83 neurons, 21 were also orthodromically activated--8 by the CeA and 3 by the LH. Additional neurons were excited (n = 5) or inhibited (n = 8) by these forebrain nuclei but not antidromically activated. Taste stimuli were: 0.032 M sucrose, 0.032 M sodium chloride (NaCl), 0.032 M quinine hydrochloride (QHCl), and 0.0032 M citric acid. Among the 34 orthodromically activated neurons, more sucrose-best neurons were excited than inhibited, whereas the opposite occurred for citric-acid- and QHCl-best cells. Neurons inhibited by the forebrain responded significantly more strongly to citric acid and QHCl than cells excited by these sites. The effects of electrical stimulation were mimicked by microinjection of DL-homocysteic acid, indicating that cells at these forebrain sites were responsible for these effects. These data demonstrate that many individual PbN gustatory neurons project to both the LH and CeA and that these areas modulate the gustatory activity of a subset of PbN neurons. This neural substrate is likely involved in the modulation of taste activity by physiological and experiential factors.

Action Potentials↗

Low-dose furosemide modulates taste responses in the nucleus of the solitary tract of the rat.

Taste-evoked neural responses in the nucleus of the solitary tract (NST) are subject to both excitatory and inhibitory modulation by physiological conditions that influence ingestion. Treatments that induce sodium appetite predominantly reduce NST gustatory responsiveness to sapid stimuli. When sodium appetite is aroused with 10 mg of the diuretic furosemide (Furo), however, NST gustatory neurons exhibit an enhanced responsiveness to NaCl. In addition to inducing a sodium appetite, 10 mg Furo supports a conditioned taste aversion (CTA). A lower, 2-mg dose of Furo induces an equivalent sodium appetite, but not a CTA. To determine whether the anomalous electrophysiological results reflected the adverse effects of the 10-mg dose, we replicated the original experiment but instead used 2 mg of Furo. In chronically prepared, lightly anesthetized rats, the responses of 49 single NST neurons to 12 taste stimuli were recorded after subcutaneous injections of either 2 mg Furo or saline. There was no effect of treatment on NST neural responses to the four standard taste stimuli. In the NaCl concentration series, however, 2 mg Furo evoked significantly higher responses to the two highest concentrations of NaCl. There was no effect of treatment in the sucrose concentration series. Thus, unlike other methods that induce a sodium appetite, Furo increases NST neural responsiveness to NaCl. At least as far as the first central relay, sodium appetite apparently does not depend on specific changes in the sensory neural code for taste.

Animals↗

Coexpression of carcinoembryonic antigen and E-cadherin in colorectal adenocarcinoma with liver metastasis.

Carcinoembryonic antigen (CEA) has been suggested as a metastatic activator in colorectal carcinoma, whereas the E-cadherin expression is downregulated in a variety of carcinomas. CEA and E-cadherin expressions were simultaneously assessed with regard to tumor progression in the various sites of colorectal carcinomas with liver metastasis. Twenty-six consecutive patients who had colorectal carcinoma with liver metastasis underwent curative surgery for primary tumor and liver metastasis. CEA and E-cadherin expression were identified on immunohistochemical staining using the labeled streptavidin-biotin method. Their mRNA expression was also detected by RT in situ PCR using one-step reverse transcription-polymerase chain reaction (RT-PCR). CEA and E-cadherin expression scores in the tumor center were greater than those in the tumor margin in both primary tumor and liver metastasis (P<0.001 to 0.006). CEA expression scores were closely associated with E-cadherin expression scores on the corresponding tumor site (P<0.001 to 0.017). CEA and E-cadherin mRNA expression was greatest in the hepatocytes adjacent to liver metastasis, next greatest in the primary tumor, and least in the liver metastasis (P<0.001 to 0.002). CEA mRNA expression was also closely correlated with E-cadherin mRNA expression in the primary tumor (P<0.001) and in the adjacent hepatocytes of the liver metastasis (P=0.018). Patients with a lesser CEA expression score in the liver metastasis margin appeared to have a longer disease-free survival period than did those with a greater CEA expression score. Expression of CEA and E-cadherin was closely correlated with the mRNA levels. Furthermore, these correlations may be implicated in the tumor progression of colorectal carcinoma considering their biological properties.

Adenocarcinoma↗

Monophyletic clade of HIV-1 subtype B in Korea: evolutionary pressure or single introduction?

We have previously shown that many of the nef sequences from Korean HIV-1 subtype B carriers were grouped together in phylogenetic tree analyses. To determine whether this pattern was originated from either a single HIV-1-infected person or some biological pressure which directs the HIV-1 genomic mutation by the Korean specific immunological characters, we analyzed nef sequences from HIV-1-infected individuals with different time intervals. Thirty-two out of 46 analyzed patients formed a Korean monophyletic (KM) clade with 93% bootstrapping value. Eighteen patients' nef sequences were analyzed 1-9 years after first analysis. None of the patients shifted their clade from the first clustered clade (KM or non-KM), and all of the re-analyzed isolates were clustered close to the first analyzed clade. Isolates of the KM dade and non-KM clade in nef analysis showed the same pattern as in env analysis. Phylogenetic clustering evidences from both nef and C2/V3 trees strongly support the idea that introduction of the KM clade in subtype B strains originated from a common source. Thus, treatment and development of an AIDS vaccine may be somewhat easier than in other countries with multiple strains of HIV-1.

Biological Evolution↗

Natural polymorphisms of protease in protease inhibitor-naive HIV-1 infected patients in Korea: a novel L63M in subtype B.

To establish a baseline for monitoring resistance mutation to protease inhibitors (PI), we determined protease(PR) sequences in peripheral blood mononuclear cells obtained from 43 PI-naive Korean HIV-1 infected patients. Interestingly, phylogenetic analysis revealed that 41 of the sequences belonged to subtype B, one belonged to subtype A, and one was unique, not clustering with any subtype. Thirty-one (76%) of the 41 sub-type B sequences formed a subclade within subtype B, a so-called "Korean B cluster." Polymorphisms were observed at 34 (34.3%) of the PR codons. One patient (2.3%) harbored a primary resistance-conferring mutation, L90M along with L63P and A71V, and all 43 strains showed some secondary associated with drug resistance. The percentage of patients with 7, 5, 4, 3, 2, and 1, resistance mutations were 2%, 2%, 14%, 23%,37%, and 9%, respectively. A novel polymorphism in subtype B, L63M was detected in two patients. Another patient showed a gross deletion (257 bp) after codon 91. The average genetic distance of the 41 subtype B sequences to the HXB2 sequence was 3.0% (range, 1.0-5.1%). Six hemophiliacs were infected with a domestic strain of HIV-1 subtype B, while the other two hemophiliacs were infected with nondomestic subtype B and had lived outside Korea. Although this is the first report on the molecular nature of PR in Korea, there is also a need to establish baselines for nonsubtype B HIV-1.

Adolescent↗

Descending influences from the lateral hypothalamus and amygdala converge onto medullary taste neurons.

The lateral hypothalamus (LH) and the central nucleus of the amygdala (CeA) exert an influence on many aspects of ingestive behavior. These nuclei receive projections from several areas carrying gustatory and viscerosensory information, and send axons to these nuclei as well, including the nucleus of the solitary tract (NST). Gustatory responses of NST neurons are modulated by stimulation of the LH and the CeA, and by several physiological factors related to ingestive behavior. We investigated the effect of both LH and CeA stimulation on the activity of 215 taste-responsive neurons in the hamster NST. More than half of these neurons (113/215) were modulated by electrical stimulation of the LH and/or CeA; of these, 52 cells were influenced by both areas, often bilaterally. The LH influenced more neurons than the CeA (101 versus 64 cells). Contralateral stimulation of these forebrain areas was more often effective (144 responses) than ipsilateral (74). Modulatory effects were mostly excitatory (102 cells); 11 cells were inhibited, mostly by ipsilateral LH stimulation. A subset of these cells (n = 25) was examined for the effects of microinjection of DL-homocysteic acid (DLH), a glutamate receptor agonist, into the LH and/or CeA. The effects of electrical stimulation were completely mimicked by DLH, indicating that cell somata in and around the stimulating sites were responsible for these effects. Other cells (n = 25) were tested for the effects of electrical stimulation of the LH and/or CeA on the responses to taste stimulation of the tongue (32 mM sucrose, NaCl and quinine hydrochloride, and 3.2 mM citric acid). Responses to taste stimuli were enhanced by the excitatory influence of the LH and/or CeA. These data demonstrate that descending influences from the LH and CeA reach many of the same cells in the gustatory NST and can modulate their responses to taste stimulation.

Action Potentials↗

Gustatory projections from the nucleus of the solitary tract to the parabrachial nuclei in the hamster.

Taste-responsive cells in the nucleus of the solitary tract (NST) either project to the parabrachial nuclei (PbN) of the pons, through which taste information is transmitted to forebrain gustatory nuclei, or give rise to axons terminating locally within the medulla. Numerous anatomical studies clearly demonstrate a substantial projection from the rostral NST, where most taste-responsive cells are found, to the PbN. In contrast, previous electrophysiological studies in the rat have shown that only a small proportion (21-45%) of taste-responsive NST cells are antidromically activated from the PbN, suggesting that less than half the cells recorded from the NST are actually involved in forebrain processing of gustatory information. In the present experiment we investigated the projections from the NST to the PbN electrophysiologically in urethane anesthetized hamsters. Responses of 101 single neurons in the rostral NST were recorded extracellularly following lingual stimulation with 32 mM NaCl, sucrose and quinine hydrochloride (QHCl) and 3.2 mM citric acid. The taste-responsive region of the PbN was identified electrophysiologically and stimulated with a concentric bipolar electrode to antidromically activate each NST cell. Of the 101 taste-responsive NST cells, 81 (80.2%) were antidromically activated from the ipsilateral PbN. The mean firing rates to taste stimulation and the spontaneous activity of these projection neurons were significantly greater than those of non-projecting cells. Every sucrose-best neuron in the sample projected to the PbN. The mean conduction velocity of the 23 QHCl-best neurons was significantly lower than that of the other 58 PbN projection neurons, suggesting that the most QHCl-responsive cells are a subset of smaller neurons. These data show that a large majority of NST cells responsive to taste stimulation of the anterior tongue project to the gustatory subdivisions of the PbN and that these cells have the most robust responses to gustatory stimulation.

Action Potentials↗

Taste responses of neurons in the hamster solitary nucleus are modulated by the central nucleus of the amygdala.

Previous studies have shown a modulatory influence of forebrain gustatory areas, such as the gustatory cortex and lateral hypothalamus, on the activity of taste-responsive cells in the nucleus of the solitary tract (NST). The central nucleus of the amygdala (CeA), which receives gustatory afferent information, also exerts descending control over taste neurons in the parabrachial nuclei (PbN) of the pons. The present studies were designed to investigate the role of descending amgydaloid projections to the NST in the modulation of gustatory activity. Extracellular action potentials were recorded from 109 taste-responsive cells in the NST of urethan-anesthetized hamsters and analyzed for a change in excitability following electrical and chemical stimulation of the CeA. Electrical stimulation of the CeA orthodromically modulated 36 of 109 (33.0%) taste-responsive NST cells. An excitatory response was observed in 33 (30.28%) cells. An initial decrease in excitability to electrical stimulation of the CeA, suggestive of postsynaptic inhibition, was observed in three (2.75%) NST taste cells. NST cells modulated by the CeA were significantly less responsive to taste stimuli than cells that were not. Many of these cells were under the modulatory influence of the contralateral CeA (28/36 = 77.8%) as well as the ipsilateral (22/36 = 61.1%); 14 (38.9%) were excited bilaterally. Latencies for excitation were longer after ipsilateral than after contralateral CeA stimulation. Microinjection of DL-homocysteic acid (DLH) into the CeA mimicked the effect of electrical stimulation on each of the nine cells tested: DLH excited eight and inhibited one of these electrically activated NST cells. Application of subthreshold electrical stimulation to the CeA during taste trials increased the taste responses of every CeA-responsive NST cell (n = 7) tested with this protocol. These effects would enhance taste discriminability by increasing the signal-to-noise ratio of taste-evoked activity.

Amygdala↗

Taste responses of neurons of the hamster solitary nucleus are enhanced by lateral hypothalamic stimulation.

Gustatory responses in the brain stem are modifiable by several physiological factors, including blood insulin and glucose, intraduodenal lipids, gastric distension, and learning, although the neural substrates for these modulatory effects are not known. Stimulation of the lateral hypothalamus (LH) produces increases in food intake and alterations in taste preference behavior, whereas damage to this area has opposite effects. In the present study, we investigated the effects of LH stimulation on the neural activity of taste-responsive cells in the nucleus of the solitary tract (NST) of the hamster. Bipolar stimulating electrodes were bilaterally implanted in the LH, and the responses of 99 neurons in the NST, which were first characterized for their taste sensitivities, were tested for their response to both ipsilateral and contralateral LH stimulation. Half of the taste-responsive cells in the NST (49/99) were modulated by LH stimulation. Contralateral stimulation was more often effective (41 cells) than ipsilateral (13 cells) and always excitatory; 10 cells were excited bilaterally. Six cells were inhibited by ipsilateral stimulation. A subset of these cells (n = 13) was examined for the effects of microinjection of DL-homocysteic acid (DLH), a glutamate receptor agonist, into the LH. The effects of electrical stimulation were completely mimicked by DLH, indicating that cell somata in and around the LH are responsible for these effects. Other cells (n = 14) were tested for the effects of electrical stimulation of the LH on the responses to stimulation of the tongue with 0.032 M sucrose, NaCl, and quinine hydrochloride, and 0.0032 M citric acid. Responses to taste stimuli were more than doubled by the excitatory influence of the LH. These data show that the LH, in addition to its role in feeding and metabolism, exerts descending control over the processing of gustatory information through the brain stem.

Animals↗