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Biomedical subjects

H S Choi

Publications and source records attributed to H S Choi.

At least 37 records · Page 2Linked to original sources

The orphan nuclear receptor small heterodimer partner as a novel coregulator of nuclear factor-kappa b in oxidized low density lipoprotein-treated macrophage cell line RAW 264.7.

Small heterodimer partner (SHP), specifically expressed in liver and a limited number of other tissues, is an unusual orphan nuclear receptor that lacks the conventional DNA binding domain. In this work, we found that SHP expression is abundant in murine macrophage cell line RAW 264.7 but was suppressed by oxidized low density lipoprotein (oxLDL) and its constituent 13-hydroxyoctadecadienoic acid, a ligand for peroxisome proliferator-activated receptor gamma. Furthermore, SHP acted as a transcription coactivator of nuclear factor-kappa B (NF kappa B) and was essential for the previously described NF kappa B transactivation by palmitoyl lysophosphatidylcholine, one of the oxLDL constituents. Accordingly NF kappa B, which was transcriptionally active in the beginning, became progressively inert in oxLDL-treated RAW 264.7 cells as oxLDL decreased the SHP expression. Thus, SHP appears to be an important modulatory component to regulate the transcriptional activities of NF kappa B in oxLDL-treated, resting macrophage cells.

Animals↗

Olefinic vs. aromatic pi-H interaction: a theoretical investigation of the nature of interaction of first-row hydrides with ethene and benzene.

The nature and origin of the pi-H interaction in both the ethene (olefinic) and benzene (aromatic) complexes of the first-row hydrides (BH(3), CH(4), NH(3), H(2)O, and HF) has been investigated by carrying out high level ab initio calculations. The results indicate that the strength of the pi-H interaction is enhanced as one progresses from CH(4) to HF. Unlike conventional H-bonds, this enhancement cannot be simply explained by the increase in electrostatic interactions or the electronegativity of the atom bound to the pi H-bonded proton. The contributions of each of the attractive (electrostatic, inductive, dispersive) and repulsive exchange components of the total binding energy are important. Thus, the inductive energy is highly correlated to the olefinic pi-H interaction as we progress from CH(3) to HF. On the other hand, both electrostatic and inductive energies are important in the description of the aromatic pi-H interaction. In either case, the contribution of dispersion energies is vital to obtain an accurate estimate of the binding energy. We also elaborate on the correlation of various interaction energy components with changes in geometries and vibrational frequencies. The red-shift of the nu(Y-H) mode is highly correlated to the inductive interaction. The dramatic increase in the exchange repulsion energies of these pi complexes as we progress from CH(4) to HF can be correlated to the blue-shift of the highly IR active out-of-plane bending mode of the pi system.

Journal Article↗

A functional retinoic acid response element (RARE) is present within the distal promoter of the rat gonadotropin-releasing hormone (GnRH) gene.

We previously demonstrated that all-trans-retinoic acid (all-trans-RA) regulates gonadotropin-releasing hormone (GnRH) release and gene expression in rat hypothalamic fragments and GT1-1 neuronal cells. Promoter analysis of rat GnRH gene revealed that the enhancing effect of all-trans-RA on GnRH transcription is mediated by cis-elements localized within --1640/--1438 of the rat GnRH promoter. In the present study, we attempted to localize functional retinoic acid response elements (RAREs) within the all-trans-RA-responsive region of the rat GnRH gene. Sequence analysis showed that there exist three putative repeats of AGGTCA-related sequences (--1637/--1617, --1579/--1562, and --1494/--1470) within this promoter sequence. Among them, only the --1494/--1470 sequence could compete the specific binding of GT1-1 nuclear extracts to the consensus RARE (direct repeat of AGGTCA with a 5-bp spacer, DR-5) and vice versa in electrophoretic mobility shift assays. In addition, like consensus RARE, the --1494/--1470 sequence could confer all-trans-RA responsiveness when inserted into the upstream region of SV40 promoter. Treatment of GT1-1 cells with all-trans- or 9-cis-RA increased the specific bindings of GT1-1 nuclear extracts to the consensus RARE and to the --1494/--1470 sequence while not affecting the specific binding to the cAMP response element (CRE). Both retinoids induced RARbeta gene expression in GT1-1 cells. The --1494/--1470 sequence (5'-TCTTAGGACTCTGTGTGACCTAAGA) is similar to the direct repeat of TGACCT (complementary sequence of AGGTCA) with a spacer of 5 bp (i.e. DR-5 in the reverse orientation). A mutation of the second core recognition motif of the --1494/--1470 sequence to a more divergent one from consensus RARE (from TGACCT to TTACAT) abolished the responsiveness to all-trans-RA, whereas a mutation of first core recognition motif to a more TGACCT-like sequence (from AGGACT to TGAACT) increased the responsiveness to all-trans-RA. These results indicate that the --1494/--1470 sequence is indeed a weak but functional RARE of the modified DR-5 type. Taken together, these data indicate that all-trans-RA enhances GnRH transcription via functional RARE present in the distal region of the GnRH promoter.

Animals↗

Cloning and characterization of cDNAs encoding the GnRH1 and GnRH2 precursors from bullfrog (Rana catesbeiana).

We have isolated the cDNAs encoding the GnRH1 and GnRH2 precursors, respectively, from bullfrog (Rana catesbeiana) brain. The first cDNA consists of 648 bp and contains an open-reading frame of 270 nucleotides, encoding the bullfrog GnRH1 precursor. The second cDNA consists of 1053 bp and contains an open-reading frame of 255 nucleotides, encoding the bullfrog GnRH2 precursor. Both types of bullfrog GnRH precursor have a similar molecular architecture as observed in other GnRH precursors, consisting of a signal peptide, followed by the GnRH decapeptide, a conserved carboxy-terminal amidation and proteolytical processing site, and a GnRH-associated peptide (GAP). In addition, we have identified a third cDNA, containing 24 additional nucleotides in its GAP-coding region. Genomic PCR and sequence analysis confirmed that this cDNA represents an alternative splice variant of the bullfrog GnRH2-precursor pre-mRNA. The bullfrog GnRH1 precursor exhibits 60% and less than 40% amino acid identity to its Xenopus and mammalian counterparts, respectively, whereas the bullfrog GnRH2 precursor displays 50% to 60% amino acid identity to that of its nonmammalian counterparts, but shares only 25% amino acid identity with its mammalian counterparts. Northern blot analysis revealed a single GnRH1-precursor mRNA species of approximately 0.75 kilobases, expressed in bullfrog forebrain, and a single GnRH2-precursor mRNA species of approximately 1.1 kilobases, expressed in bullfrog midbrain/hindbrain. Furthermore, both bullfrog GnRH-precursor mRNAs exhibited a differential spatiotemporal expression pattern. Genomic Southern blot analysis indicated that both bullfrog GnRH genes are present as single copy genes. This is the first report on the molecular cloning of a GnRH2-precursor cDNA from an amphibian species. In addition, we present data showing that alternative splicing is utilized to generate different GnRH2-precursor mRNAs. J. Exp. Zool. 289:190-201, 2001.

Alternative Splicing↗

Three distinct types of GnRH receptor characterized in the bullfrog.

It has been proposed recently that two types of GnRH receptors (GnRHR) exist in a particular species. Here we present data demonstrating that at least three types of GnRHR are expressed in a single diploid species, the bullfrog. Three different cDNAs, encoding distinct types of bullfrog GnRHR (bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3), were isolated from pituitary and hindbrain of the bullfrog. BfGnRHR-1 mRNA was expressed predominantly in pituitary, whereas bfGnRHR-2 and -3 mRNAs were expressed in brain. The bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3 proteins have an amino acid identity of approximately 30% to approximately 35% with mammalian GnRHRs and approximately 40% to approximately 50% with nonmammalian GnRHRs. Interestingly, bfGnRHR-2 has an 85% amino acid homology with Xenopus GnRHR. Less than 53% amino acid identity was observed among the three bfGnRHRs. All isolated cDNAs encode functional receptors because their transient expression in COS-7 cells resulted in a ligand-dependent increase in inositol phosphate production. Notably, all three receptors exhibited a differential ligand selectivity. For all receptors, cGnRH-II has a higher potency than mGnRH. In addition, salmon GnRH also has a strikingly high potency to stimulate all three receptors. In conclusion, we demonstrated the presence of three GnRHRs in the bullfrog. Their expression in pituitary and brain suggests that bfGnRHRs play an important role in the regulation of reproductive functions in the bullfrog.

Amino Acid Sequence↗

Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects.

Mutations in several genes encoding transcription factors of the hepatocyte nuclear factor (HNF) cascade are associated with maturity-onset diabetes of the young (MODY), a monogenic form of early-onset diabetes mellitus. The ability of the orphan nuclear receptor small heterodimer partner (SHP, NR0B2) to modulate the transcriptional activity of MODY1 protein, the nuclear receptor HNF-4alpha, suggested SHP as a candidate MODY gene. We screened 173 unrelated Japanese subjects with early-onset diabetes for mutations in this gene and found five different mutations (H53fsdel10, L98fsdel9insAC, R34X, A195S, and R213C) in 6 subjects as well as one apparent polymorphism (R216H), all present in the heterozygous state. Interestingly, all of the subjects with the mutations were mildly or moderately obese at onset of diabetes, and analysis of the lineages of these individuals indicated that the SHP mutations were associated with obesity rather than with diabetes. Therefore, an additional group of 101 unrelated nondiabetic subjects with early-onset obesity was screened for mutations in the SHP gene. Two of the previously observed mutations (R34X and A195S) and two additional mutations (R57W and G189E) were identified in 6 subjects, whereas no mutations were identified in 116 young nondiabetic lean controls (P = 0.0094). Functional studies of the mutant proteins show that the mutations result in the loss of SHP activity. These results suggest that genetic variation in the SHP gene contributes to increased body weight and reveal a pathway leading to this common metabolic disorder in Japanese.

Adolescent↗

Association between Helicobacter pylori infection and the risk of gastric cancer in the Korean population: prospective case-controlled study.

BACKGROUND: Gastric cancer is still the most common malignant tumor in Koreans. Although many reports have supported the association of Helicobacter pylori infection and the development of gastric cancer, few studies have been adjusted by variable factors such as age. sex, education, and economic status. Furthermore, most results from areas with a high incidence of gastric cancer, such as China and Korea, have failed to document any relationship between H. pylori infection and gastric cancer. We conducted a prospective case-controlled study, with controls matched for and adjusted by age, sex, education, and economic status, to evaluate the causal relationship between H. pylori infection and gastric cancer in Korean people. METHODS: From March 1997 to October 1998, 136 consecutive patients with gastric cancer, diagnosed by endoscopic histology, and 136 age- and sex-matched control subjects, confirmed to be free of gastric cancer by endoscopy during the same period, were enrolled in the study. The presence of H. pylori infection was determined by enzyme immunoassay (EIA) serology test. RESULTS: Seventy-two of the 136 gastric cancer patients (53%) were positive for H. pylori infection and 54 of the 136 control subjects (40%) were positive for H. pylori infection. The odds ratio (OR), adjusted by variable risk factors, such as age, sex, education, and economic status, for gastric cancer in H. pylori-infected patients was 1.82 (95% confidence internal [CI], 1.10-3.00; P = 0.019). The age- and sex-matched OR by conditional logistic regression was 1.6 (95% CI., 1.01-2.53; P = 0.043). CONCLUSIONS: H. pylori infection may be one of the important risk factors for the development of gastric cancer in Korea, an area of high prevalence of H. pylori infection and a high incidence of gastric cancer.

Adult↗

Devising an objective nasal vibration test for nasal resonatory disorders.

The present study investigates the clinical applicability of a new device, which objectively measured nasal resonating vibration via piezoelectric vibratory sensor in 10 normal volunteers, 10 patients with definite hypernasality, and 10 nasal polyposis patients. For the assessment of the hypernasality, the ratio of /ng/ to /a/ as well as the ratio of /mama/ to /papa/ passages were used. For the evaluation of hyponasality, the ratio of nasal vibration postinduced to preinduced cul-de-sac resonation was calculated. The control group showed the ratio of /ng/ to /a/ and /mama/ to /papa/ passages to be larger than 8, whereas the ratio was markedly lower in the hypernasality group. The vibratory signals of /a/ and /ng/ increased markedly in the control and the hypernasality groups after inducing cul-de-sac resonation, but the change was minimal in the hyponasality group. This new device could detect nasal resonatory disorders and readily differentiate between hypernasality and hyponasality.

Humans↗

Functional characteristics of a new electrolarynx "Evada" having a force sensing resistor sensor.

Electrolarynxes have been used as one of the rehabilitation methods for laryngectomees. Earlier electrolarynxes could not alter frequency and intensity simultaneously during conversation. Recently, we developed an electrolarynx named "Evada" (prototype so far) using a force sensing resistor (FSR) sensor that can control both frequency and intensity simultaneously during conversation. Employing three types of electrolarynxes (Evada, Servox-inton, Nu-vois), this study was undertaken to examine the functional characteristics of Evada for the normal control group and for laryngectomess. Five laryngectomees and five normal adults were asked to express three sentences (declarative sentence, "You stay here.", interrogative sentence, "You stay here?", and imperative sentence, "You! Stay here.") using three types of electrolarynxes. Frequency and intensity changes between the first and last vowels in the three sentences were calculated and analyzed statistically by paired t test. The frequency changes in the interrogative and imperative sentences were more prominent in Evada than in Servox-inton and Nu-vois. The intensity changes in the interrogative and imperative sentences were also more prominent in Evada than in Servox-inton and Nu-vois. Evada controls frequency and/or intensity by having the subject press the control button(s). Therefore, Evada appears to be better at producing intonation and contrastive stress than Nu-vois and Servox-inton.

Equipment Design↗

Localization and characterization of acharan sulfate in the body of the giant African snail Achatina fulica.

Acharan sulfate is a glycosaminoglycan (GAG), having the structure -->4)-2-acetamido-2-deoxy-alpha-D-glucopyranose(1-->4)-2-sulfo-alpha-L-idopyranosyluronic acid (1-->, isolated from the body of the giant African snail Achatina fulica. This GAG represents 3-5% of the dry weight of this snail's soft body tissues. Frozen sections and polyester wax sections of the snail's body were stained by Alcian blue-periodic acid-Schiff's reagent (PAS) to localize acharan sulfate. Alcian blue staining indicated that GAG was mainly secreted into the outer surface of the body from internal granules. A highly mucous material was collected and treated and the acharan sulfate was recovered by ethanol and cetyl pyridinium chloride precipitation. Crude acharan sulfate was purified by DEAE-Sephacel ion-exchange chromatography. Depolymerization of intact mucus and purified acharan sulfate fractions by heparin lyase II (heparitinase I) from Flavobacterium heparinum produced an unsaturated disaccharide as a major product, establishing the repeating unit of acharan sulfate. These results demonstrate that mucus in the granule and secreted to the outside of the body is composed entirely of acharan sulfate.

Alcian Blue↗

Characterization of the odor-active volatiles in citrus Hyuganatsu (Citrus tamurana Hort. ex Tanaka).

The volatile components of Hyuganatsu (Citrus tamurana Hort. ex Tanaka) peel oil, isolated by cold-pressing, were investigated by chemical and sensory analyses. According to chemical analysis by GC and GC-MS, limonene (84.0%) was the most abundant compound, followed by gamma-terpinene (6.9%), myrcene (2.2%), alpha-pinene (1.2%), and linalool (1.0%). Monoterpene hydrocarbons were predominant in Hyuganatsu peel oil. The odor-active volatiles in Hyuganatsu flavor were studied by GC-olfactometry and omission tests. The characteristic flavor was present in the oxygenated fraction. Flavor dilution (FD) factors of the volatile flavor components of the Hyuganatsu cold-pressed oil were determined by aroma extraction dilution analysis (AEDA). Furthermore, relative flavor activity was investigated by means of FD factor and weight percent. Ten kinds of odor compounds having Hyuganatsu-like aroma were detected by AEDA: limonene, linalool, octanol, neral, neryl acetate, tridecanal, trans-carveol, cis-nerolidol, trans,trans-farnesyl acetate, and trans,trans-farnesol. Linalool and octanol were regarded as the most odor-active or key compounds of Hyuganatsu aroma. Diluted solutions of linalool and octanol of approximately 2 ppm gave a fresh and fruity aroma note similar to Hyuganatsu flavor.

Chromatography, Gas↗

Modulation of the levels of NMDA receptor subunit mRNA and the bindings of [3H]MK-801 in rat brain by chronic infusion of subtoxic dose of MK-801.

The effects of continuous infusion of NMDA receptor antagonist MK-801 on the modulation of NMDA receptor subunits NR1, NR2A, NR2B, and NR2C were investigated by using in situ hybridization study. Differential assembly of NMDA receptor subunits determines their functional characteristics. Continuous intracerebroventricular (i.c.v.) infusion with MK-801 (1 pmol/10 microl/h) for 7 days resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels without producing stereotypic motor syndromes. The levels of NR1 mRNA were significantly increased (9-20%) in the cerebral cortex, striatum, septum, and CA1 of hippocampus in MK-801-infused rats. The levels of NR2A mRNA were significantly decreased (11-16%) in the CA3 and dentate gyrus of hippocampus in MK-801-infused rats. In contrast to NR2A, NR2B subunit mRNA levels were increased (10-14%) in the cerebral cortex, caudate putamen, and thalamus. However, no changes of NR2C subunits in cerebellar granule layer were observed. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased (12-25%) significantly in almost all brain regions except in the thalamus and cerebellum after 7 days infusion with MK-801. These results suggest that region-specific changes of NMDA receptor subunit mRNA and [3H]MK-801 binding are involved in the MK-801-infused adult rats.

Animals↗

A case of testicular tunica albuginea cyst with psammoma body.

Cystic testicular masses have been considered rare but due to advances in ultrasonographic technologies their incidence has risen. Many testicular cystic masses are benign but there is a chance of malignancy. Psammoma bodies are found in various malignancies that occur in the genital tract of women but rarely in men. We report a case of testicular tunica albuginea cyst with psammoma bodies.

Adult↗

Pelvic aspergillosis with tubo-ovarian abscess in a renal transplant recipient.

Common clinical manifestations of aspergillosis in renal transplant recipients are fever and pulmonary infiltrates, but involvement of the reproductive system is rare. We report a case of pelvic aspergillosis with tubo-ovarian abscess in a renal transplant patient. The patient received a cadaveric renal transplantation, and two episodes of acute rejection were treated with methylprednisolone pulse therapy. Surgical biopsy specimens of pelvic abscess detected by ultrasonogram and CT revealed Aspergillus. With amphotericin B treatment, the patient is well with normalization of erythrocyte sedimentation rate and C-reactive protein.

Abdominal Abscess↗

Cnidicin, a coumarin, from the root of Angelica koreana, inhibits the degranulation of mast cell and the NO generation in RAW 264.7 cells.

Cnidicin (1) and five related coumarins were isolated from the root extract of Angelica koreana (Umbelliferae) as active principles responsible for the inhibitory effect on the degranulation process of cultured mast cells. Cnidicin (1) demonstrated a significant inhibition upon the release of beta-hexosaminidase from the cultured RBL-2H3 cells in a dose dependent manner (IC50 value, 25 microM) and upon the nitric oxide production from the activated RAW264.7 cells (IC50 value, 7.5 microM). In agreement with this, cnidicin inhibited the expression of nitric oxide synthase in RAW264.7 cells.

Animals↗

Effects of bergenin, the major constituent of Mallotus japonicus against D-galactosamine-induced hepatotoxicity in rats.

The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against D-galactosamine (GalN)-induced liver damage in rats. Bergenin (50, 100 and 200 mg/kg) was given orally once daily for 7 successive days and then GalN 400 mg/kg was injected intraperitoneally to rats at 24 and 96 h after the final administration of bergenin. Pretreatment with bergenin reduced the increased enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase, gamma-glutamyltransferase and the elevated level of malondialdehyde induced by GalN. Bergenin restored the decreased hepatic contents of glutathione as well as the decreased activities of glutathione S-transferase and glutathione reductase by GalN towards normalization, suggesting that the hepatoprotective effects of bergenin may consist in maintaining adequate levels of hepatic glutathione for the removal of xenobiotics. The present results indicate that bergenin has hepatoprotective effects against GalN-induced hepatotoxicity in rats.

Animals↗

LH induces orphan nuclear receptor Nur77 gene expression in testicular Leydig cells.

The orphan nuclear receptor Nur77 (NR4A1) is a member of the nuclear receptor superfamily and plays an important role in the regulation of genes involved in steroidogenesis and cell death. Northern blot analysis revealed that the expression of Nur77 mRNA was increased after puberty in mouse testis, and hCG treatment of peripubertal animals induced this gene expression in the testis. Moreover, LH treatment induced a transient increase in Nur77 mRNA, and this induction was LH dose dependent in mouse Leydig tumor cell line, K28. Western blot analysis showed that LH transiently induced Nur77 protein. The protein kinase inhibitor H-89, bisindolymaleimide I, and wortmannin strongly inhibited this inductive effect of LH on Nur77 gene expression. Transient transfection assay demonstrated that LH significantly increased the Nur77 promoter-driven luciferase reporter activity in a dose-dependent manner, and LH also increased the activity of a luciferase reporter gene driven by a promoter containing multi copies of a Nur77-responsive element. Moreover, EMSA showed that Nur77 DNA-binding activity was increased in response to LH. Finally, overexpression of dominant negative Nur77 reduced LH-mediated progesterone biosynthesis. Taken together, these results demonstrate that LH induces Nur77 gene expression, and Nur77 may play an important role in the LH-mediated steroidogenesis in Leydig cells.

Animals↗

Gonadotropin regulation of NGFI-B messenger ribonucleic acid expression during ovarian follicle development in the rat.

NGFI-B is an immediate-early gene that encodes an orphan nuclear receptor. The present study was designed to examine the localization and gonadotropin regulation of NGFI-B expression in the rat ovary. Northern blot analysis of ovaries obtained from prepubertal rats revealed the increased expression of NGFI-B during prepubertal development. Treatment of immature rats with PMSG, however, decreased ovarian NGFI-B expression. The major cell types expressing NGFI-B messenger RNA were thecal cells of follicles in different sizes. In contrast, treatment of PMSG-primed rats with human (h) CG resulted in the rapid and transient stimulation of ovarian NGFI-B messenger RNA, reaching a peak within 1 h. In situ hybridization analysis revealed that hCG treatment induced the expression of NGFI-B in granulosa cells of preovulatory follicles. Treatment of cultured preovulatory follicles in vitro with LH further confirmed the time- and dose-dependent stimulation of NGFI-B messenger RNA and protein. LH-stimulated NGFI-B expression in preovulatory follicles was abolished by alpha-amanitin, but was superinduced by cycloheximide. Furthermore, treatment of adult cycling rats with pentobarbital abolished NGFI-B expression on proestrus, and exogenous administration of hCG restored it, indicating the role of the preovulatory surge of LH in the stimulation of NGFI-B expression. These results demonstrate the cell type-specific expression and gonadotropin induction of NGFI-B in granulosa cells of preovulatory follicles and suggest a role for NGFI-B in the ovulatory process.

Animals↗