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Biomedical subjects

H Cho

Publications and source records attributed to H Cho.

At least 73 records · Page 4Linked to original sources
PubMed1999

Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034, 7-carboxymethyloxy-3', 4', 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD: two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3 to approximately 3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 mg/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

Acetic Acid↗
PubMed1999

2- or 6-(1-azidoalkyl)-5,8-dimethoxy-1,4-naphthoquinone: synthesis, evaluation of cytotoxic activity, antitumor activity and inhibitory effect on DNA topoisomerase-I.

6-(1-azidoalkyl)-DMNQ derivatives compared to 2-(1-azidoalkyl)-DMNQ isomers, exhibited higher cytotoxic activity against L1210 mouse leukemia cells and stronger inhibition of DNA topoisomerase-I (TOPO-I), suggesting involvement of steric hindrance. However, similar antitumor activity against mice bearing S-180 cell was shown by 2- and 6-(1-azidoalkyl)-DMNQ derivatives.

Animals↗
PubMed1999

The general transcription factors IIA, IIB, IIF, and IIE are required for RNA polymerase II transcription from the human U1 small nuclear RNA promoter.

RNA polymerase II transcribes the mRNA-encoding genes and the majority of the small nuclear RNA (snRNA) genes. The formation of a minimal functional transcription initiation complex on a TATA-box-containing mRNA promoter has been well characterized and involves the ordered assembly of a number of general transcription factors (GTFs), all of which have been either cloned or purified to near homogeneity. In the human RNA polymerase II snRNA promoters, a single element, the proximal sequence element (PSE), is sufficient to direct basal levels of transcription in vitro. The PSE is recognized by the basal transcription complex SNAPc. SNAPc, which is not required for transcription from mRNA-type RNA polymerase II promoters such as the adenovirus type 2 major late (Ad2ML) promoter, is thought to recruit TATA binding protein (TBP) and nucleate the assembly of the snRNA transcription initiation complex, but little is known about which GTFs other than TBP are required. Here we show that the GTFs IIA, IIB, IIF, and IIE are required for efficient RNA polymerase II transcription from snRNA promoters. Thus, although the factors that recognize the core elements of RNA polymerase II mRNA and snRNA-type promoters differ, they mediate the recruitment of many common GTFs.

Animals↗
PubMed1999

Treatment of severe postpartum hemorrhage by rectally administered gemeprost pessaries.

OBJECTIVE: To assess the efficacy of rectally administered gemeprost pessaries in the treatment of severe postpartum hemorrhage. DESIGN: Retrospective analysis of a twelve month period in which all patients having postpartum hemorrhage treated with rectal gemeprost were analyzed. SETTING: Royal Darwin Hospital, Northern Territory, Australia. POPULATION: Fourteen women with established postpartum hemorrhage not responding to oxytocine and ergometrine regimens, or not responsive to oxytocine and having contraindications to ergometrine. MAIN OUTCOME MEASURES: Per vaginum bleeding with continued postpartum hemorrhage; adverse patient reactions to gemeprost; need for operative intervention. RESULTS: All patients who were treated with rectally administered gemeprost pessaries had cessation of bleeding per vaginum. There were no adverse side effects noted from the medication and no patient required surgical treatment. CONCLUSIONS: Rectally administered gemeprost administered pessaries appear to be safe and effective method of treating severe postpartum hemorrhage in those patients in whom the standard oxytocic regimens fail. This form of treatment may avoid the need for parenteral prostaglandins or surgical intervention.

Administration, Rectal↗
PubMed1999

Role of p53 gene mutation in tumor aggressiveness of intracranial meningiomas.

The mutations that occur in the p53 tumor suppressor gene have been studied in various human malignant tumors. However, little is known about this gene in meningiomas. To investigate the relationship and frequency of p53 gene mutations, the p53 polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) and immunohistochemical study were performed on the 41 intracranial meningiomas (21 benign, 11 atypical, and 9 malignant). The higher the p53 protein expression rate, the poorer the histologic grade (9.5%, 72.7%, and 88.9% in benign, atypical and malignant meningioma, respectively) (p=0.000). The p53 protein expression rate was higher in recurrent meningioma (71.4%) than in nonrecurrent meningioma (10.5%) (p=0.002). PCR-SSCP method was performed in positive p53 protein immunoreactivity cases. p53 gene mutation rate was higher in the atypical (62.5%) and malignant (25%) meningiomas than in the benign meningioma (0%) (p=0.232). Also, the rate was higher in recurrent menigioma (20%) than in nonrecurrent meningioma (0%) (o=0.495). Among five to eight exons of the p53 gene, the mutation was observed on exon 7 more frequently. In conclusion, p53 immunoreactivity and p53 gene mutation are closely correlated with histologic grade and histologic atypia of intracranial meningiomas. p53 gene mutation would be considered as a useful marker to detect the progression of intracranial meningiomas.

Brain Neoplasms↗
PubMed1999

Comparison of rocuronium and vecuronium pretreatment for prevention of fasciculations, myalgia and biochemical changes following succinylcholine administration.

BACKGROUND: The purpose of this study was to assess the effect of rocuronium pretreatment on the succinylcholine-induced fasciculations, myalgia and biochemical changes, and to compare it with vecuronium pretreatment. METHODS: We have studied 60 female patients undergoing minor elective surgery, in a prospective double blinded method. Three groups of 20 patients each was pretreated with either saline (control group), rocuronium 0.05 mg/kg (rocuronium group) or vecuronium 0.007 mg/kg (vecuronium group). Three min after the pretreatment, 1.5 mg/kg succinylcholine was injected. Single twitch responses to electrical stimulation were measured. Serum potassium and creatine kinase were respectively measured 5 min after succinylcholine and 24 h after operation. Fasciculations and myalgia on postoperative day 1 and day 2 were evaluated. RESULTS: The incidence of fasciculations was lowest in the rocuronium group, followed by the vecuronium group, and was highest in the control group. The incidence of myalgia on postoperative day 1 was lower in the rocuronium and vecuronium groups than the control group. The increase of serum creatine kinase was similar among the three groups, but there was no increase in serum potassium concentration in any group. No differences of the single twitch responses to electrical stimulation were found between the rocuronium and vecuronium groups. CONCLUSIONS: Rocuronium pretreatment was more effective in reducing fasciculations than was vecuronium pretreatment, but both were equally effective in preventing myalgia on postoperative day 1. This difference may reflect the differential activities of rocuronium and vecuronium at the neuromuscular junction. The increase of creatine kinase was not attenuated by any regimen.

Adult↗
PubMed1998

Evidence for the location of bicyclomycin binding to the Escherichia coli transcription termination factor Rho.

The commercial antibiotic bicyclomycin (Bcm) has been shown to target the essential transcription termination factor Rho in Escherichia coli. Little is known about the Bcm binding domain in Rho. A recent structure-activity relationship study led us to evaluate the reductive amination probe, 5a-(3-formylanilino)dihydrobicyclomycin (FD-Bcm). Biochemical studies showed that FD-Bcm possessed inhibitory activities comparable to Bcm in Rho-dependent ATPase and transcription termination assays. Incubation of Rho with FD-Bcm, ATP, and poly(C) followed by NaBH4 reduction and dialysis led to an appreciable loss of ATPase activity. Inclusion of Bcm with FD-Bcm in the reductive amination reaction protected Rho, indicating that Bcm and FD-Bcm competed for the same binding site in Rho. Incubation of Rho with FD-Bcm and poly(C) followed by NaBH4 reduction provided a sample with residual ATPase activity (12%). Mass spectrometric analysis indicated the presence of two proteins in an approximate 1.2:1 ratio, whose masses corresponded to wild-type Rho (47,010 Da) and lysine-modified Rho (47,417 Da), respectively. Trypsin digestion of the Rho sample followed by high performance liquid chromatography separation and tandem mass spectrometry analysis identified the site of modification as Lys181 within the combined tryptic fragment, Gly-Leu-Ile-Val-Ala-Pro-Pro-Lys-Ala-Gly-Lys (residues 174-184). Similar analysis of a lesser modified sample (following incubation with inclusion of ATP) showed that addition had again occurred at Lys181. These findings provide the first structural information concerning the site of Bcm binding in Rho.

Adenosine Triphosphatases↗
PubMed1998

Elucidation of conditions allowing conversion of penicillin G and other penicillins to deacetoxycephalosporins by resting cells and extracts of Streptomyces clavuligerus NP1.

Using resting cells and extracts of Streptomyces clavuligerus NP1, we have been able to convert penicillin G (benzylpenicillin) to deacetoxycephalosporin G. Conversion was achieved by increasing by 45x the concentration of FeSO4 (1.8 mM) and doubling the concentration of alpha-ketoglutarate (1.28 mM) as compared with standard conditions used for the normal cell-free conversion of penicillin N to deacetoxycephalosporin C. ATP, MgSO4, KCl, and DTT, important in cell-free expansion of penicillin N, did not play a significant role in the ring expansion of penicillin G by resting cells or cell-free extracts. When these conditions were used with 14 other penicillins, ring expansion was achieved in all cases.

Adenosine Triphosphate↗
PubMed1998

Auditory pathway and auditory brainstem response in mice lacking NMDA receptor epsilon 1 and epsilon 4 subunits.

There is considerable evidence that the N-methyl-D-aspartate receptor (NMDAR) is a component of excitatory amino acid synapses in the ascending auditory pathway. The availability of mice that are defective in NMDAR epsilon 1 or NMDAR epsilon 4 subunit paves the way for investigations on the role of this receptor in auditory function. Non-radioactive in situ hybridization was used in the parent C57/6J wild strain to determine if these subunits are normally expressed in cochlear nucleus (CN) and superior olivary complex (SOC) and to confirm their absence in the respective mutant mice. Evoked auditory brainstem response (ABR) to normal acoustic stimulation was investigated to assess function. In situ hybridization revealed the expression of NMDAR epsilon 1 and epsilon 4 subunits mRNAs in major neuronal types in the CN and SOC of the wild type mice while epsilon 1 and epsilon 4 expression were absent in their respective mutant mice. The ABR threshold for the epsilon 1 mutant mice was similar to that of wild type mice however the threshold for the epsilon 4 mutant mice was significantly elevated. These results suggest a role for the NMDAR epsilon 4 in normal auditory functions while the NMDAR epsilon 1 may have a less critical function under normal conditions.

Animals↗
PubMed1998

N-carbamoyl-L-glutamate plus L-arginine can protect ammonia intoxication in rats with reduced functional liver mass.

We previously reported the protective effect of N-carbamoyl-L-glutamate plus L-arginine in rats given a lethal dose (LD99.9) of ammonium acetate (Kim, S. et al., Proc. Natl. Acad. Sci. 69, 3530-3533, 1971; ref.1). The present study was undertaken to find out whether the same compounds could also be effective even after the functional mass of the liver was significantly reduced. Thus, the protective effect of these compounds in 70% partial hepatectomized rats following the injection of sublethal dose of ammonium acetate was assessed. The mixture could significantly decrease blood ammonia level compared with PBS-injected control group. In addition, abnormal behaviors observed in the control rats were significantly improved. The protective effect on the behavioral change seemed to be closely related with their effect on blood ammonia level, showing a strong correlation between the blood ammonia level and the behavioral score. The findings provide a rational basis for the clinical use of N-carbamoyl-L-glutamate plus L-arginine in the prevention and treatment of hyperammonemia encountered in liver diseases.

Acetates↗
PubMed1998

Specificity of alcohol dehydrogenases for sulfoxides.

Sulfoxides inhibit horse liver alcohol dehydrogenase (EqADH) by binding to the enzyme-NADH complex. X-ray crystallography suggests that sulfoxides make a cation-pi interaction with the benzene ring of Phe-93 [Cho et al. (1997) Biochemistry 36, 382-389]. Structure-function relationships were examined with seven different sulfoxides binding to five human enzymes (alpha, beta1, gamma2, pi, and sigma) and three mutated forms of the horse enzyme. The human gamma2 enzyme, EqADH, and EqADH with Phe-93 replaced with Trp were selectively and strongly inhibited (Ki </= 1 microM) by the 3-butyl or hexyl derivatives of thiolane 1-oxide. The other human enzymes (all with Thr-48) and EqADH with Ser-48 substituted with Thr had relatively lower affinities for the thiolane 1-oxides due to close contact of the methyl group of Thr-48 with a carbon adjacent to the sulfoxide sulfur. EqADH binds the S isomers of 3-butylthiolane 1-oxides, hexyl methyl sulfoxide, and phenyl methyl sulfoxide more tightly than the R isomers, but EqADH with Phe-93 substituted with Ala and the human alpha enzyme (with Ala-93) prefer (R)-phenyl methyl sulfoxide, apparently because the phenyl ring fits into the space near residue 93. EqADH and the enzymes with Phe-93 replaced with Ala or Trp had similar affinities for sulfoxides, indicating that the contribution of the cation-pi interaction to binding is small or compensated for by altered interactions. Ab initio calculations also suggest that the interaction of a sulfoxide with benzene is relatively weak.

Alanine↗
PubMed1998

Biphasic changes in F3/contactin expression in the gerbil hippocampus after transient ischemia.

We studied changes in expression of F3/contactin (F3), a neuron-specific adhesion molecule, in the gerbil hippocampus after transient forebrain ischemia for 5 min. By immunohistochemical techniques using F3 antibody, we found a biphasic change in immunoreactivity for F3 in the CA1 area after ischemia. Western blotting of F3 protein showed a similar biphasic change. F3 immunoblots decreased to 67% of the control at 1 week, but then they increased and attained 159% at 3 weeks and 152% at 5 weeks after ischemia. Immunoreactivity of a neurofilament (NF145) showed a similar biphasic change to F3 but to a lesser extent. In contrast, microtubule-associated protein 2 (MAP2) immunoreactivity uniformly decreased after ischemia. In situ hybridization revealed that F3 messenger RNA (mRNA) hybridization signals in CA1 area were greatly reduced 1 week after ischemia, while the signals in the CA3 area were unchanged and even increased 3 weeks after ischemia. Damage to CA3 neurons by hyperthermic ischemia blocked the F3 increase in area CA1. Our results suggest that the initial decrease in F3 following ischemia reflects loss of CA1 neurons and the late increase in F3, which shows that a similar time course with neurofilaments may be caused by neurite sprouting.

Animals↗
PubMed1998

Retinoic acid regulates gonadotropin-releasing hormone (GnRH) release and gene expression in the rat hypothalamic fragments and GT1-1 neuronal cells in vitro.

The present study attempts to examine the possible involvement of retinoic acid (RA) in the regulation of gonadotropin-releasing hormone (GnRH) release and gene expression in the rat hypothalamic fragments and GT1-1 neuronal cells in vitro. During a short-term period (2h), RA (0.01-1 microM) increased GnRH release in a dose-related manner. Time-course experiments showed that RA rapidly increased GnRH release by 30 min in both cells. RA-induced GnRH release was slowly attenuated in the next incubation period in hypothalamic fragments, but rapidly returned to control levels in GT-1 cells. In hypothalamic fragments, GnRH mRNA levels decreased, but in GT1-1 cells, no change in GnRH mRNA levels was observed. We then extended the incubation time to see any changes in GnRH mRNA levels by RA in GT1-1 cells. In a long term (up to 48 h), RA increased GnRH mRNA levels in a dose- and time-related manner. Significant increase in GnRH mRNA levels by RA (at higher than 10 nM) was observed within 12h. Transient transfection experiments with a luciferase reporter vector containing more than 3 kb of the rat GnRH 5'-flanking region (-3002 to +88) revealed that RA also increased the rat GnRH promoter activity in a similar dose-and time-dependent manner, suggesting that increases in GnRH mRNA levels are attributable, at least in part, to the enhanced gene transcription. The promoter analysis with the 5'-deletional constructs demonstrated that cis-elements responsible for the RA action may reside within -1640/-1438 of the rat GnRH promoter, where multiple direct or palindromic arrangements of the AGGTCA-related sequences exist. We also showed that GT1-1 cells as well as the hypothalamic tissues express mRNA for multiple subtypes of retinoid receptors, and that reporter plasmids with three copies of the strong retinoic acid response element (RARE) were activated by 80 folds upon treatment with RA in GT1-1 cells, suggesting that retinoid receptors in GT1-1 cells are functional. Taken together, the present study strongly suggests that RA is an important regulator of the GnRH neurons.

Animals↗
PubMed1998

NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription.

A complex that represses activated transcription and contains the human homologs of the yeast Srb7, Srb10, Srb11, Rgr1, and Med6 proteins was isolated. The complex is devoid of the Srb polypeptides previously shown to be components of the yeast Mediator complex that functions in transcriptional activation. The complex phosphorylates the CTD of RNA polymerase II (RNAPII) at residues other than those phosphorylated by the kinase of TFIIH. Moreover, the complex specifically interacts with RNAPII. The interaction is not mediated by the CTD of RNAPII, but is precluded by phosphorylation of the CTD. Our results indicate that the complex is a subcomplex of the human RNAPII holoenzyme. We suggest that the RNAPII holoenzyme is a transcriptional control panel, integrating and responding to specific signals to activate or repress transcription.

Amino Acid Sequence↗
PubMed1998

Analysis of the interaction of the novel RNA polymerase II (pol II) subunit hsRPB4 with its partner hsRPB7 and with pol II.

Under conditions of environmental stress, prokaryotes and lower eukaryotes such as the yeast Saccharomyces cerevisiae selectively utilize particular subunits of RNA polymerase II (pol II) to alter transcription to patterns favoring survival. In S. cerevisiae, a complex of two such subunits, RPB4 and RPB7, preferentially associates with pol II during stationary phase; of these two subunits, RPB4 is specifically required for survival under nonoptimal growth conditions. Previously, we have shown that RPB7 possesses an evolutionarily conserved human homolog, hsRPB7, which was capable of partially interacting with RPB4 and the yeast transcriptional apparatus. Using this as a probe in a two-hybrid screen, we have now established that hsRPB4 is also conserved in higher eukaryotes. In contrast to hsRPB7, hsRPB4 has diverged so that it no longer interacts with yeast RPB7, although it partially complements rpb4- phenotypes in yeast. However, hsRPB4 associates strongly and specifically with hsRPB7 when expressed in yeast or in mammalian cells and copurifies with intact pol II. hsRPB4 expression in humans parallels that of hsRPB7, supporting the idea that the two proteins may possess associated functions. Structure-function studies of hsRPB4-hsRPB7 are used to establish the interaction interface between the two proteins. This identification completes the set of human homologs for RNA pol II subunits defined in yeast and should provide the basis for subsequent structural and functional characterization of the pol II holoenzyme.

Amino Acid Sequence↗