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Biomedical subjects

D Chun

Publications and source records attributed to D Chun.

At least 19 recordsLinked to original sources
PubMed2002

Local action of estrogen and thyroid hormone on vasoactive intestinal peptide (VIP) and galanin gene expression in the rat anterior pituitary.

Neuropeptides act within the pituitary as autocrine or paracrine factors, modulating the synthesis and release of primary pituitary hormones, and possibly regulating cell proliferation and/or plasticity. Manipulation of the endocrine status of rats produces dramatic long-term changes in the pituitary expression of several peptides, including the neuropeptides galanin and vasoactive intestinal peptide (VIP). Whether or not these changes are caused indirectly by hypothalamic factors, or by hormone actions directly in the pituitary, has been only partially addressed. To determine if estrogen or thyroid hormone can act directly within the pituitary to regulate VIP and galanin gene expression, cultured female rat pituitary cells were treated with 10 nM 1,17 beta-estradiol (E2) or triiodothyronine (T(3)). E2 treatment for three days resulted in an approximate 5-fold and 7-fold increase in VIP and galanin mRNA, respectively. In contrast, T(3) treatment reduced the mRNA levels of these neuropeptides to approximately 40% and 30% of control values. A time course study indicated that the actions of estrogen on VIP and galanin mRNA, and of thyroid hormone on VIP mRNA were readily apparent after 24h. The rat pituitary tumor cell line RC-4B/C was found to express easily detectable levels of galanin but not VIP mRNA. Galanin gene expression in these cells was moderately increased by E2 and decreased by T(3). Transfection of a series of luciferase plasmids containing 5 kb to 131 bp of the bovine galanin promoter fused to luciferase revealed cell-type specific enhancer sequences located between -452 and -131 bp of the galanin gene transcription start site. However, transfected plasmids were minimally responsive to E2 and T(3) treatment. Overall the results suggest that E2 and T(3) exert significant local actions in the pituitary on VIP and galanin gene expression. The bovine galanin gene fragment used in these studies contains a potential pituitary cell-type specific enhancer, but appears to lack strong E2-and T(3)-responsive sequences.

Animals↗
PubMed2001

VIP gene transcription is regulated by far upstream enhancer and repressor elements.

SK-N-SH human neuroblastoma subclones differ widely in basal and second messenger induction of the gene encoding the neuropeptide vasoactive intestinal peptide (VIP). These differences were recapitulated by a chimeric gene which consisted of 5.2 kb of the human VIP gene 5' flanking sequence fused to a reporter. Subsequent gene deletion experiments revealed several regulatory regions on the gene, including a 645-bp sequence located approximately 4.0 upstream from the transcription start site. Here we examined this upstream region in detail. Inhibitory sequences were found to be present on each end of the 645-bp fragment. When removed, basal transcription increased more than 50-fold. Subsequent deletion/mutation analysis showed that the 213-bp fragment contained at least two enhancer elements. One of these was localized to an AT-rich 42-bp sequence shown by others to bind Oct proteins in neuroblastoma cells, while the other corresponded to a composite AP-1/ets element. In addition to these enhancers, a 28-bp sequence on the 213-bp fragment with no apparent homology to known silencers inhibited transcription. The studies provide molecular details of a complex regulatory region on the VIP gene that is likely to be used to finely tune the level of gene transcription in vivo.

5' Untranslated Regions↗
PubMed2001

Evidence that integrins contribute to multiple stages in the consolidation of long term potentiation in rat hippocampus.

Three structurally distinct groups of antagonists were used to test the hypothesis that integrin adhesion receptors play an essential role in consolidating (stabilizing) long term potentiation of the Schaffer collaterals in rat hippocampus. Comparisons were made of percent potentiation at antagonist-treated versus control sites within CA1 stratum radiatum of the same hippocampal slice. Function blocking antibodies against the alpha5 subunit of the fibronectin receptor had no effect on baseline responses or initial potentiation but resulted in a >30% reduction, relative to within-slice control long term potentiation, 45 min later. Larger reductions were recorded in separate experiments continued for 4 h after the induction of potentiation. Alpha(v) and alpha2 subunit antibodies did not reliably affect the stabilization of potentiation. An antagonist peptide with preference for beta1 integrins produced a slowly developing decline of the type seen with alpha5 antibodies. A cyclic peptide antagonist reduced potentiation within 10 min of induction and caused an almost 40% decrease over 45 min. Two disintegrins (snake toxins that potently block integrins) were very effective in preventing the consolidation of long term potentiation: echistatin reduced potentiation by >70%, while triflavin caused approximately 50% decrease. The suppressing effects of echistatin were concentration-dependent, obtained with treatment after induction, and much more rapid than the effects of antibodies. Rapid declines in potentiation were particularly evident when the two disintegrins were applied together. These results indicate that hippocampal fibronectin receptors (alpha5/beta1 integrin) contribute importantly to a slowly developing phase of long term potentiation consolidation. They also suggest that other integrins are critical to aspects of consolidation occurring in the first few minutes after induction.

Animals↗
PubMed1999

GABAB receptor antagonism: facilitatory effects on memory parallel those on LTP induced by TBS but not HFS.

The present experiments used CGP 35348, a selective GABAB receptor antagonist with a significantly higher affinity for post- versus presynaptic receptors, to dissociate the role of antagonist concentration versus stimulation mode in determining whether GABAB receptor blockade facilitates or suppresses long-term potentiation (LTP). The antagonist was applied by pressure ejection to one of two recording sites in area CA1 of hippocampal slices before LTP was induced at both sites with either theta burst or high-frequency stimulation (TBS or HFS). TBS produced a dose-dependent facilitation of potentiation that turned into depression at the highest concentration tested, a result reflecting the dose-dependent balance between the drug's postsynaptic disinhibitory effect and its action on presynaptic autoreceptors regulating the release of GABA. In contrast, HFS-induced LTP increased monotonically with drug concentration, suggesting that blockade of postsynaptic GABAB receptors is the only factor contributing to HFS-induced LTP. To test the relevance of the two sets of LTP results, we performed behavioral studies examining the effect of different dosages of antagonist on spatial retention and found that memory was enhanced at intermediate dosages but not at very low and high concentrations, reminiscent of the bell-shaped dose-response curve obtained for TBS-induced LTP. These findings are consistent with the notion that LTP induced by electrical stimulation modeled after endogenous theta-modulated activity patterns bears more relevance to behavior than does potentiation induced by arbitrary tetanic trains.

Analysis of Variance↗
PubMed1998

Unilateral hippocampal ablation at birth causes a reduction in contralateral LTP.

Subcortical damage in neonates often has more severe consequences than in adults. Unilateral electrolytic hippocampal lesions in adult rats typically result in transient memory deficits, whereas neonatal lesions cause lasting memory impairments. We hypothesized that unilateral lesions made at birth may affect synaptic physiology in the contralateral hippocampus. Consequently, the ability to sustain long-term potentiation (LTP), a form of synaptic plasticity believed to underlie certain forms of memory, was compared between slices from the remaining hippocampus of rats lesioned as newborns and as adults. Initial studies showed that a train of 10 stimulation bursts patterned after the hippocampal theta rhythm produced robust and stable LTP both in slices from controls and rats lesioned at birth. However, a theta burst pattern of stimulation closer to intrinsic physiology (five burst pairs separated by 30 s each), induced significantly less LTP in slices from rats lesioned at birth compared to those from controls and rats lesioned as adults. To investigate possible mechanisms underlying the deficit, the degree of paired-pulse facilitation (PPF) as well as the amount of depolarization occurring between two successive theta bursts were analyzed. The lesion did not detectably change PPF characteristics, suggesting that presynaptic mechanisms are normal. However, the extent to which a burst response was increased by a prior burst was significantly diminished in slices from rats lesioned at birth compared to those from controls and rats lesioned as adults, indicating that postsynaptic factors involved in the initial triggering events of LTP are affected by the lesion. Reduced ability to sustain LTP in the remaining hippocampus may contribute to impaired memory function after unilateral neonatal hippocampal lesion.

Animals↗
PubMed1998

Time-dependent reversal of long-term potentiation by an integrin antagonist.

The integrin antagonist Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) was applied by local ejection to one of two recording sites in hippocampal slices at various times before and after long-term potentiation (LTP) was induced at both sites with theta burst stimulation. Applications 10 min before, immediately after, and 10 min after induction caused LTP at the experimental site to decay steadily relative to that at the within-slice control site. However, application at 25 min or more after induction had no detectable effect on potentiation. Similar results were obtained when the integrin antagonist was perfused into the slice rather than applied locally. The time period after induction during which GRGDSP interfered with LTP consolidation corresponds to that during which LTP is susceptible to reversal by low-frequency afferent stimulation and newly formed memories are vulnerable to various disruptive treatments. Comparable experiments using a peptide that blocks an extracellular binding site of neural cell adhesion molecules (NCAMs) did not yield time-dependent reversal of LTP; i.e., an antagonist that interacts with the fourth immunoglobulin-like domain reduced LTP when applied before induction but not afterward. Moreover, LTP formation occurred normally in the presence of an antibody against the fibronectin repeat domain of NCAM. These results suggest that integrin activation and signaling occurring over several minutes after LTP induction are necessary for stabilizing synaptic potentiation and by inference may be required for the conversion of new memories into a not readily disrupted state.

Amino Acid Sequence↗
PubMed1997

Arg-Gly-Asp-Ser-selective adhesion and the stabilization of long-term potentiation: pharmacological studies and the characterization of a candidate matrix receptor.

Peptides known to block the extracellular interactions of adhesion receptors belonging to a subclass of the integrin family were tested for their effects on the stabilization of long-term potentiation (LTP) in hippocampal slices. Theta burst stimulation delivered after infusions of Gly-Ala-Val-Ser-Thr-Ala (GAVSTA) resulted in a potentiation effect that decayed steadily over a period of 40 min; LTP elicited in the presence of inactive control peptides remained stable over this time period. GAVSTA had no detectible influence on baseline responses, induction processes, or the initial degree of potentiation. Infusions of integrin antagonists after application of theta bursts also resulted in the occurrence of a decremental form of LTP. Affinity chromatography was then used in an effort to identify targets of the structurally dissimilar integrin blockers that disrupt LTP stabilization. Both integrin antagonists Gly-Arg-Gly-Asp-Ser-Pro and GAVSTA eluted a major species of 55 kDa (synaptegrin-1) from GRGDSP-affinity columns that had been loaded with solubilized synaptic membranes; lesser concentrations of three polypeptides of approximately 20, 27, and 30 kDa were also collected. Synaptegrin-1 was labeled by antibodies to the RGDS-binding integrin alpha5beta1. In addition, the synaptegrin, as well as the 27 kDa, protein was found to copurify with pre- and postsynaptic markers during the isolation of forebrain synaptosomes. These results indicate that a matrix recognition event occurring several minutes after induction of LTP is a necessary step in the stabilization of potentiated synapses; they also identify an integrin-like matrix receptor of 55 kDa that may contribute to this event.

Animals↗
PubMed1996

Factors regulating the reversibility of long-term potentiation.

Theta burst stimulation (TBS) produces an extremely stable form of long-term potentiation (LTP). In contrast, a brief episode of single-pulse stimulation at theta frequency [theta pulse stimulation (TPS)] has been demonstrated to reverse LTP in area CA1 of slices and freely moving animals without causing depression when administered to nonpotentiated pathways. The present in vitro studies confirm these results and establish that the susceptibility of LTP to reversal and the degree of depotentiation are time-dependent. Specifically, a 1 min train of TPS delivered 30 sec after LTP induction produced an almost complete and lasting depotentiation but had increasingly less impact at longer delays and virtually no effect at 30 min. Increasing the duration of TPS did not cause more depotentiation. However, pharmacological facilitation of AMPA receptor-mediated currents significantly enhanced the strength of the reversal process and allowed TPS to produce robust depotentiation up to 30 min after LTP induction. The reversal effect was selective to potentiated synapses receiving TPS, was reversible, and was not blocked by NMDA receptor antagonism. Additional experiments indicated that AMPA receptor facilitation promotes depotentiation by enhancing an active process triggered by TPS that reverses expression without extending the time course of consolidation. These results suggest that the mechanisms responsible for LTP reversal are linked to the amplitude and/or duration of fast excitatory currents mediated by synaptic AMPA receptors and are effective up to the completion of LTP stabilization.

Animals↗
PubMed1996

The influence of size or number of biopsies on rapid urease test results: a prospective evaluation.

BACKGROUND: The optimal number or size of endoscopic biopsies for use in rapid urease testing has not been established. Postulating that increasing the amount of tissue sampled would improve diagnostic yield and hasten development of a positive test, we compared urease testing with one regular biopsy, two regular biopsies, and one "jumbo" forceps biopsy. METHODS: One hundred fifty patients undergoing endoscopy had three sets of prepyloric biopsies placed in a CLOtest: one regular forceps biopsy, two regular forceps biopsy, and one large-channel jumbo forceps biopsy. Biopsies were then taken for two independent histologic examinations. Disagreements were resolved by another examiner. RESULTS: Eighty-nine patients (59%) had Helicobacter pylori infection by histology; interobserver agreement was 90% with kappa = 0.78. The mean time to a positive test was 5.3 +/- 0.9 hours for one regular biopsy, 3.2 +/- 0.7 hours for two regular biopsies, and 3.8 +/- 0.8 hours for one jumbo biopsy (p < 0.01 for two regular, one jumbo vs. one regular biopsy). Compared to one regular biopsy, the urease test was positive at least 30 minutes earlier in 56% of the patients with two regular biopsies and 54% with one jumbo biopsy. Sensitivities for one regular versus two regular biopsies were 1 hour, 19% versus 33% (p = 0.059); 2 hours, 38% versus 49% (p = 0.17); 3 hours, 48% versus 60% (p = 0.18); and 24 hours, 75% versus 79% (p > 0.20). CONCLUSIONS: Doubling the amount of tissue in the CLOtest hastens the development of a positive test by approximately 1 1/2 to 2 hours; tests become positive at least 30 minutes earlier in over 50% of the patients. Low cost, ease, and excellent specificity make the rapid urease test a valuable diagnostic tool. Nevertheless, if used as a "rapid" diagnostic test (read within 3 hours of biopsy), it is associated with a false negative rate of approximately 40%.

Adult↗
PubMed1994

Fulminant amebic colitis. A morphologic study of four cases.

PURPOSE: The morphologic features of fulminant amebic colitis are poorly documented. In this report, we describe the clinical and pathologic findings in four of these cases. METHODS: The surgical pathology reports and accompanying histologic slides were examined from four patients who underwent surgical resections for fulminant amebic colitis. Clinical information was obtained from the patients' medical records. RESULTS: Large, geographic mucosal ulcers were typically present and were accompanied by yellow-green pseudomembranes. The muscularis externa was usually attenuated and necrotic, imparting a "wet blotting paper" consistency. Large numbers of amebic trophozoites were present within the inflammatory exudates. The mucosa adjacent to and undermined by the ulcers was often hemorrhagic or inflamed, resembling ischemic colitis or idiopathic inflammatory bowel disease, respectively. Two patients died within four weeks of their surgery. A third patient died one year later as a result of AIDS-related complications. The remaining patient has been lost to follow-up. CONCLUSION: An uncommon but life-threatening manifestation of intestinal amebiasis is a fulminant colitis. Early surgical intervention and intensive antiamebic chemotherapy are essential for efficacious management.

AIDS-Related Opportunistic Infections↗
PubMed1990

Patterns of mandibular movements in subjects with craniomandibular disorders.

Mandibular movements were evaluated for border and functional movements in 24 adult normal subjects and 26 adult patients with muscle pain associated with a craniomandibular disorder. The mandibular incisor position was tracked with an electromagnetic system in three planes by use of either a Myotronic Kinesiograph or a Siemens Sirognathograph instrument while the subject sat in an upright position. In the normal subjects, the maximum movements of the mandible in lateral, protrusive, and vertical directions were compared with the envelope of movement during speech and mastication. The range of the rest position was 1 to 5 mm in relation to the intercuspal position; the range of maximum excursion during speech was 30% to 36% of maximum opening; the vertical extent of excursion during mastication was 18% to 90% of the maximum vertical opening dependent on the bolus. Protrusive movements were straight forward, dividing the angle evenly between left and right laterotrusion. Laterotrusive movements were of equal length and similar to the length of protrusion. Twenty-six patients with muscle pain, in many instances, demonstrated asymmetry in the length of laterotrusive movements. Different pathways for moving the mandible away from the intercuspal position and returning to this position could be seen during laterotrusion. Unequal laterotrusive excursions and asymmetrical, nonparallel movement patterns for mandibular protrusion and retrusion were often observed. In contrast, the extent of the speech envelope and the envelope of mastication were similar to that of the controls.

Adolescent↗
PubMed1986

Supine change in arterial oxygenation in patients with chronic obstructive pulmonary disease.

In normal subjects, recumbent PaO2 differs from upright PaO2 as a function of the relationship between FRC and closing volume. However, in patients with lung disease, the factors controlling PaO2 change. Furthermore, the distribution of airway closure does not strictly reflect gravitational gradients in pleural pressure. Hence, we evaluated the effects of recumbency on PaO2 in patients with advanced COPD. We conducted pulmonary function tests and measured PaO2, AaPO2, change from upright to supine FRC, VE, cardiac output (QT), and mixed venous oxygen saturation (SvO2). Eight patients with COPD in whom PaO2 decreased in the supine position (Group I) were compared with 8 patients with COPD in whom PaO2 improved in the recumbent position (Group II); the only anthropometric difference between the groups was greater body weight in Group II (p less than 0.05). Pulmonary function was comparable in the 2 groups. In both groups, FRC decreased with recumbency, but supine FRC and delta FRC did not differ between groups nor correlate significantly with PaO2, AaPO2, or venous admixture (QVA/QT). Supine SVO2 increased in both groups, but supine QT increased significantly only in Group I. In Group II, recumbent QVA/QT did not change significantly, whereas recumbent QVA/QT increased (p less than 0.02) in Group I. The cause for increased QVA/QT in Group I was reduced VE plus increased QT while supine; in contrast, by maintaining a higher supine VE and by not increasing QT significantly, an increase in QVA/QT was prevented in Group II subjects, an increase that would otherwise have overwhelmed the benefits of increased recumbent SVO2 on PaO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1984

R plasmids conferring multiple drug resistance from shigella isolated in Korea.

The majority (85%) of shigella isolated in 1980 and 1981 in Korea were Shigella flexneri, the others were Sh. sonnei (14%) with only a small number of Sh. dysenteriae. Only 14 of the 459 strains of shigella isolated were susceptible to all 12 drugs tested, and 445 were resistant to three or more drugs. Strains multiply resistant to the six drugs, chloramphenicol (Cm), tetracycline (Tc), streptomycin (Sm), sulfisomidine (Su), ampicillin (Ap) and trimethoprim (Tp) were most frequently encountered, followed by those resistant to Cm, Tc, Sm, Su and Tp. The complete patterns of resistance to drugs except nalidixic acid and rifampin in approximately 73% of drug-resistant strains were co-transferred to Escherichia coli by conjugation, indicating that the resistance was R plasmid-mediated. Randomly selected R plasmids conferring various patterns of resistance markers were tested for the incompatibility groups, and almost all of them were classified into Inc FII. Two of three R plasmids conferring resistance to Cm, Tc, Sm and Su were classified into Inc B and one to Inc FII. Two R types with resistance markers of Cm, Tc, Sm and Ap were not classified with our standard plasmids used.

Anti-Bacterial Agents↗
PubMed1981

Mixed venous oxygenation, exercise, body posture, and v/q ratio in chronic obstructive pulmonary disease.

Mixed venous oxygenation (partial pressure, PVO2; saturation, SVO2) and its impact on pulmonary function at rest in the supine position (SUP), at rest in the standing position (STAND), and during maximal treadmill exercise (Emax), were studied in 41 stable patients with chronic obstructive pulmonary disease, using arterial and right heart (Swan-Ganz) catheterization. The patients represented a broad spectrum of disease severity (VC, 3.1 +/- 0.9 L; FEF 25-75, 1.0 +/- 0.7 L). It was found that: (a) venous oxygenation was uniform among different patients in the supine position at rest (PVO2, 33.8 +/- 2.4 mmHg' SVO2, 76.2 +/- 3.6%), regardless of the heterogeneity in airway obstruction, as previously reported by others; (b) venous oxygenation was also uniform in STAND (PVO2, 29.5 +/- 2.5 mmHg; SVO2, 58 +/- 3.9%) and treadmill Emax (PVO2, 22.4 +/- 3.3 mmHg; SVO2, 34.4 +/- 6%), an observation not previously reported; (c) the orthostatic mixed venous desaturation at rest was pronounced, and was nearly as great as that from STAND to Emax; (d) the potential effect of mixed venous desaturation on alveolar O2 partial pressure (PAO2) and end-capillary O2 saturation (SCO2) was not obvious from SUP to STAND, and from STAND to Emax conditions, being masked by an appropriate increase in overall V/Q ratio; (e) because of constant SCO2 and low interindividual variations of SVO2, there was a high correlation of arterial saturation (SaO2) to venous admixture (Qva/Qt, sum of true shunt and shuntlike components) for each of the conditions studied. Hence, because of high correlation of the equations relating SaO2 to Qva/Qt (r greater than 0.9), these relationships might be used for noninvasive prediction of Qva/Qt from SaO2 in patients with COPD.

Carbon Dioxide↗
PubMed1977

Drug resistance and R plasmids in Salmonella typhi isolated in Korea.

A total of 949 strains of Salmonella typhi isolated in Korea from 1968 to 1975 were tested for drug resistance and distribution of R plasmids. Resistance was mostly restricted to streptomycin (SM) and sulfisomidine (SA), singly or in combination, at a low degree. A small number of strains (1.5%) were resistant to four or more drugs: chloramphenicol (CM), tetracycline (TC), SM, SA, ampicillin (AP), and kanamycin (KM). No strain was resistant to nalidixic acid or to a 1:20 mixture of trimethoprim and sulfamethoxazole. Nor was there any strain singly resistant to CM, TC, AP, or KM. Transfer experiments of multiple-drug resistance to Escherichia coli ML1410 showed that all the strains resistant to four or more drugs carried R plasmids, whereas those weakly resistant to three or less drugs did not. The quadruply resistant strains carried one R plasmid determining CM, TC, SM, and SA resistance, and sextuply resistant ones carried two plasmids, one determining CM, TC, SM, and SA resistance and the other determining AP and KM resistance. One strain carrying a plasmid determining AP and KM resistance was also found. The transfer frequency of CM, TC, SM, and SA resistance was much higher than that of AP and KM resistance. The resistance of S. typhi was more efficiently transferred to E. coli at 25 degrees C than at 37 degrees C.

Conjugation, Genetic↗