PubMed Health⌕ Search

Biomedical subjects

C H Chiu

Publications and source records attributed to C H Chiu.

At least 55 records · Page 3Linked to original sources
PubMed2000

Discordant effect of aspirin and indomethacin on intestinal tumor burden in Apc(Min/+)mice.

Epidemiologic and animal studies indicate that sustained use of non-steroidal anti-inflammatory drugs (NSAIDs) have a chemopreventive effect against the incidence of colorectal neoplasia and subsequent mortality. We previously demonstrated that sulindac significantly reduces intestinal tumor load in Apc(Min/+)mice and the tumor regression was not necessarily correlated with prostaglandin biosynthesis. In the present study, we further investigate the relationship of NSAID treatment and tumorigenesis in the Apc(Min/+)mouse model. We demonstrate that indomethacin (9 ppm) is a very potent chemopreventive agent, reducing tumor load by 85% and significantly inhibiting basal and ex vivo prostaglandin formation (P< 0.006 and P< 0.0001, respectively). Aspirin (400 ppm) has a similar impact on reducing prostaglandin levels, but in contrast to indomethacin, is uneffective in reducing the tumor load. The data indicate a discordance between the impact of different NSAIDs on tumorigenesis in Apc(Min/+)mice.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Antagonism of arachidonic acid is linked to the antitumorigenic effect of dietary eicosapentaenoic acid in Apc(Min/+) mice.

The multiple intestinal neoplasia (Apc(Min/+)) mouse possesses a germline mutation at codon 850 of the adenomatous polyposis coli (Apc) gene resulting in the formation of a nonfunctional truncated gene product. Following a somatic mutation of the remaining wild-type allele, mice spontaneously develop approximately 40-50 tumors throughout the intestinal tract. This mouse model has been used to study intestinal tumorigenesis because this mutation is analogous to the inherited APC mutation in humans with familial adenomatous polyposis (FAP). These individuals characteristically develop numerous adenomas throughout their intestinal tracts. Only a few studies have evaluated the effects of dietary fatty acids on tumorigenesis in this animal model with varying results, and none have linked these effects to alterations in arachidonic acid (AA) metabolism. This study was designed to evaluate the antitumorigenic effect of dietary (n-3) polyunsaturated fatty acids (PUFA) in the Apc(Min/+) mouse model and to determine whether these effects are related to inhibition of AA metabolism. Male Apc(Min/+)mice were fed diets supplemented with eicosapentaenoic acid (EPA), AA or a combination of AA + EPA. Mean tumor number in the EPA group was 68% lower (P<0.05) compared with the control group, whereas AA supplementation did not significantly alter tumor load. The reduction in tumor load coincided with significant reductions in intestinal AA content and levels of prostaglandins. However, supplementing AA to the EPA diet (AA + EPA) abolished the antitumorigenic effect of EPA, increased tissue AA content fourfold and prostaglandin production two- to fourfold. These results indicate that AA is involved in tumorigenesis and suggest that EPA's ability to reduce tumor load in Apc(Min/+) mice is related to reductions in tissue AA content or its metabolism.

Analysis of Variance↗
PubMed2000

Factors associated with intestinal perforation in children's non-typhi Salmonella toxic megacolon.

BACKGROUND: To evaluate the risk factors for intestinal perforation in children with toxic megacolon caused by non-typhi Salmonella infection. METHODS: During an 11-year period we reviewed the records of children treated for non-typhi Salmonella infection. All of the subjects had positive stool culture for non-typhi Salmonella and were treated with intravenous ceftriaxone during hospitalization. Clinical data reviewed included demographic features, clinical manifestations, laboratory findings, radiologic findings, microbiology, therapeutic effect of hydration and rectal tube placement and the operative findings. Patients with toxic megacolon were defined as those having toxic appearance, diarrhea, high fever (>39 degrees C) and marked colon dilatation with maximal diameter > 1.5 times the width of the vertebra body of the first lumbar spine (L1-VB). To define the risk factors for patients with toxic megacolon complicated by intestinal perforation, patients were divided into two groups for analysis: P group, those complicated with intestinal perforation; and NP group, those without intestinal perforation. Differences in age, sex, severity of diarrhea, duration of fever, hemogram and its differential, culture, stool analysis, serum C-reactive protein (CRP), electrolytes, maximal colon diameter, medical therapy and timing of rectal tube insertion between the two groups were analyzed. Statistical analyses were conducted with chi square tests and multiple logistic regression. RESULTS: A total of 75 patients (P group, 27 patients; NP group, 48 patients) ages 4 months to 6 years were evaluated. With chi square analysis 7 variables were found to be significantly associated with intestinal perforation: age >1 year; fever >5 days; ratio of immature to total neutrophils >20%; serum CRP >200 mg/l; colon diameter >2.5 times the width of L1-VB; inadequate early hydration; and delay in rectal tube insertion. With multivariate analysis age >1 year, serum CRP >200 mg/l and colon diameter >2.5 times of width of L1-VB, inadequate early hydration and delay in rectal tube insertion were the most significant factors associated with intestinal perforation. CONCLUSION: Identification of patients with toxic megacolon associated with non-typhi Salmonella infection at risk for further intestinal perforation is possible. Early effective fluid resuscitation and rectal tube insertion may be helpful to prevent the occurrence of intestinal perforation.

Child↗
PubMed2000

Lack of evidence of an association between the carriage of virulence plasmid and the bacteremia of Salmonella typhimurium in humans.

The involvement of the virulence plasmid (pSTV) of Salmonella typhimurium in human salmonellosis was examined. Most of the 224 clinical strains isolated from the blood (53) and nonblood samples (171) contained a 90 kb or larger plasmid, most of which were pSTV. The rates of pSTV carriage in the isolates showed no statistically significant difference between those derived from the blood and those from other sources (87% vs. 83%; chi2=0.49, 0.1<P<0.9), suggesting that pSTV may not play a critical role in promoting S. typhimurium bacteremia in humans. Nine strains with representative plasmid profiles were tested for the mouse virulence. The result revealed that these clinical isolates contained all three virulent types known: the avirulent, the highly virulent when a pSTV was present, and the moderately virulent regardless of the presence or absence of pSTV. This indicated that mouse virulence of S. typhimurium did not correlate their virulence in humans. Clinical data showed that most patients with primary bacteremia had underlying immunosuppressive diseases, whereas only a few patients with secondary bacteremia had preexisting diseases (87% vs. 13%; chi2=22.73, P<0.005). It is suggested that the contribution of pSTV to S. typhimurium bacteremia in humans is likely to be limited, and both the host factor and the microbial virulence determinants on the chromosome are more important than virulence plasmid in predisposing patients to bacteremia.

Aged↗
PubMed2000

Roles of the AX(4)GKS and arginine-rich motifs of hepatitis C virus RNA helicase in ATP- and viral RNA-binding activity.

The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) possesses protease, nucleoside triphosphatase, and helicase activities. Although the enzymatic activities have been extensively studied, the ATP- and RNA-binding domains of the NS3 helicase are not well-characterized. In this study, NS3 proteins with point mutations in the conserved helicase motifs were expressed in Escherichia coli, purified, and analyzed for their effects on ATP binding, RNA binding, ATP hydrolysis, and RNA unwinding. UV cross-linking experiments indicate that the lysine residue in the AX(4)GKS motif is directly involved in ATP binding, whereas the NS3(GR1490DT) mutant in which the arginine-rich motif (1486-QRRGRTGR-1493) was changed to QRRDTTGR bound ATP as well as the wild type. The binding activity of HCV NS3 helicase to the viral RNA was drastically reduced with the mutation at Arg1488 (R1488A) and was also affected by the K1236E substitution in the AX(4)GKS motif and the R1490A and GR1490DT mutations in the arginine-rich motif. Previously, Arg1490 was suggested, based on the crystal structure of an NS3-deoxyuridine octamer complex, to directly interact with the gamma-phosphate group of ATP. Nevertheless, our functional analysis demonstrated the critical roles of Arg1490 in binding to the viral RNA, ATP hydrolysis, and RNA unwinding, but not in ATP binding.

Adenosine Triphosphatases↗
PubMed2000

Ginseng flowers stimulate progesterone production from bovine luteal cells.

Our previous report first showed evidence that polysaccharides isolated from ginseng leaves obtained from Jilin, China possess luteotropic activities. In this study, we made further investigations on the root and flowers of Korean ginseng by means of the same bioassay system described briefly as follows. Frozen-thawed bovine luteal cells (1 x 10(5) cells/ml/well) in M199 were incubated in 24-well culture plates at 37 degrees C in a 5 % CO2 incubator. Ten microl of tested drugs with 1, 10 and 100 microg/ml were added into each well. After 4- and 24-hr incubation, the media were harvested and assayed for progesterone by an enzyme immunoassay. The production of progesterone from cells is the indicator for evaluating the action of tested drugs. Results showed that hot water extracts ofginseng flowers (GF-1) with 10 to 100 microg/ml significantly increased progesterone production, whereas those from ginseng root (GR-1) could not. Crude polysaccharides (GF-2) isolated from GF-1 is the active component and the small molecules (mw < 10,000 dalton) are excluded, indicating that the ginseng root has no luteotropic activities, but the polysaccharides of ginseng flowers have.

Animals↗
PubMed1999

MDM2 and MDMX inhibit the transcriptional activity of ectopically expressed SMAD proteins.

Transforming growth factor-beta (TGF-beta) inhibits cell proliferation in many cell types, and acquisition of TGF-beta resistance has been linked to tumorigenesis. One class of proteins that plays a key role in the TGF-beta signal transduction pathway is the SMAD protein family. MDM2, a key negative regulator of p53, has recently been shown to suppress TGF-beta-induced growth arrest in a p53-independent manner. Here we show that MDM2 and the structurally related protein MDMX can inhibit the transcriptional activity of ectopically expressed SMAD1, SMAD2, SMAD3, and SMAD4. Immunofluorescence staining indicated that ectopically expressed SMAD4 was present in both the cytoplasm and nucleus, and MDM2 and NIDMX were localized mainly to the nucleus and cytoplasm, respectively. When SMAD4 was coexpressed with either MDM2 or MDMX, nuclear accumulation of SMAD4 was strikingly inhibited. We have no evidence that SMAD4 binds directly to MDM2 or MDMX; hence, the inactivation and nuclear exclusion of SMAD4 by MDM2/MDMX may involve other indirect mechanisms.

Animals↗
PubMed1999

Is Hsp90 a regulator of evolvability?

In a recent paper, Rutherford and Lindquist (1998. Nature 396:336-342) identified mutations in the Hsp90 protein that act to unmask hidden genetic variation with a variety of phenotypic effects. The Hsp90 protein has a number of properties that suggest a role in regulating the expression of genetic variation and therefore in adjusting the evolvability of the organism. In this paper we reflect upon the evolutionary feasibility of such mechanisms and suggest some possible ways of testing the adaptation-for-evolvability hypothesis in more detail. We conclude that Hsp90 holds promise as a molecular model system for the evolution of evolvability. J. Exp. Zool. ( Mol. Dev. Evol. ) 285:116-118, 1999.

Animals↗
PubMed1999

Model for the fetal recruitment of simian gamma-globin genes based on findings from two New World monkeys Cebus apella and Callithrix jacchus (Platyrrhini, Primates).

The originally embryonic gamma-globin locus duplicated and acquired a novel (fetal) pattern of expression in a defined time period (55-40 million years ago) during primate phylogeny. The objective of this study was to determine some of the factors that led to first the emergence of fetal gamma specificity and then the maintenance of different fetal gamma expression patterns in extant simian primates (e.g., human, capuchin monkey). Analyses focused on two platyrrhine (New World monkey) species: the common marmoset (Callithrix jacchus) and the brown capuchin monkey (Cebus apella), each of which has paired, non-allelic gamma loci (5'-gamma 1-gamma 2-3'). Quantitation of beta-type globin mRNAs expressed in a 4.5 week old embryo of Callithrix jacchus revealed that in addition to its primary epsilon-globin message, considerable amounts of gamma 1 message and just trace levels of gamma 2 message are present. In contrast, analyses of gamma-globin messenger RNAs expressed in a Cebus apella fetal liver indicated that gamma 2 expression is at least 120 times greater than gamma 1 expression. Using a luciferase reporter and a transient assay system, the strengths of gamma 1 and gamma 2 promoter fragments of Cebus apella were compared in erythroid (K562) and non-erythroid (HeLa) cell lines. Due to the lack of chromatin repression in a transient expression system, the results do not fully recapitulate globin expression. However, the results suggest that sequences contained within the Cebus gamma 1 and gamma 2 proximal promoter regions (-200 to +1 bp) can direct gamma transcription in both cell lines. In K562 and, to a lesser extent, in HeLa cells Cebus gamma 2 promoter fragments were significantly stronger (P < 0.01) than gamma 1 promoter fragments. This is consistent with the fact that the Cebus gamma 1 promoter contains several mutations, including a proximal CCAAT box mutation (CCAAT-->CCAAc). The epsilon-gamma 1 intergenic distances in these platyrrhines (5.4 kb in Cebus apella and 6.9 kb in Callithrix jacchus) are short, supporting the inference that it was also short in the stem simian primates. The results suggest that immediately following the gamma duplication, the gamma 1 gene of the stem simians was still embryonic and the downstream gamma 2 gene was largely silent. A further inference is that once gamma 2 accumulated regulatory mutations that disrupted binding of fetal repressors, gamma 2 was expressed fetally and, through gene conversion, passed these characteristics to the gamma 1 gene. The fetal expression of gamma 1 is most evident in catarrhines (Old World monkeys and hominoids), which preferentially express the gamma 1 locus during fetal life.

Animals↗
PubMed1999

In vitro evaluation of intracellular activity of antibiotics against non-typhoid Salmonella.

Non-typhoid salmonellae are the most common causative organisms of bacterial enteritis in children. Clinical studies have failed to show any influence of various antibiotics on the natural course of acute salmonella enteritis. Poor penetration of antibiotics into phagocytic cells that contain intracellular Salmonella spp., and possible intracellular antibiotic inactivation have been considered as possible reasons for this. In this study, we used an in vitro model to assess the intracellular activity of antibiotics against non-typhoid salmonellae. The survival of intracellular Salmonella spp. in P388D1 cells, a mouse macrophage cell line was measured in the presence of various antibiotics. Except for gentamicin, which entered phagocytes poorly, ofloxacin, azithromycin, chloramphenicol and three beta-lactam antibiotics, ampicillin, cefixime and ceftriaxone, exhibited bacteriostatic activity against susceptible intracellular Salmonella spp. at an extracellular concentration equal to the minimal inhibitory concentration (MIC). At a concentration of 10 x MIC, neither chloramphenicol nor the three beta-lactam antibiotics produced a bactericidal response; however, both ofloxacin and azithromycin were bactericidal after 8-24 h of incubation. The results showed that fluoroquinolones and new macrolides were more efficient than the other antibiotics in eradicating intracellular salmonella and might be useful agents for the treatment of non-typhoid salmonella enteritis in children. Clinical trials should be considered.

Animals↗
PubMed1999

A clinical trial comparing oral azithromycin, cefixime and no antibiotics in the treatment of acute uncomplicated Salmonella enteritis in children.

OBJECTIVE: The objective of this study was to perform a prospective, randomized, controlled study to evaluate the role of azithromycin and cefixime in the treatment of uncomplicated non-typhoid Salmonella enteritis in children. METHODOLOGY: Patients with Salmonella enteritis were randomized to receive oral azithromycin (10 mg/kg/day once daily), cefixime (10 mg/kg/day divided twice daily) or no antibiotics for 5 days. The patients were followed up for the duration of their symptoms. Stool samples were sent for culture weekly following the therapy until two consecutive negative results were obtained. Susceptibility of the isolates to antibiotics was tested by the disk diffusion method. RESULTS: Forty-two patients with acute, uncomplicated, culture-confirmed Salmonella enteritis were studied. Duration of diarrhoea and time to defervescence after the therapy were not significantly different for patients treated with azithromycin, cefixime, or no antibiotics; there also were no significant differences with respect to the rate of clearance of Salmonella from stools among the three groups. Salmonella typhimurium was the most common serotype isolated. All 42 isolates were sensitive to cefixime, while two strains (5%) were resistant to azithromycin. CONCLUSION: Azithromycin or cefixime provides no benefit to paediatric patient with uncomplicated Salmonella enteritis.

Administration, Oral↗
PubMed1999

Spread of drug-resistant Streptococcus pneumoniae in Asian countries: Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study.

Antimicrobial susceptibility of 996 isolates of Streptococcus pneumoniae from clinical specimens was investigated in 11 Asian countries from September 1996 to June 1997. Korea had the greatest frequency of nonsusceptible strains to penicillin with 79.7%, followed by Japan (65.3%), Vietnam (60.8%), Thailand (57.9%), Sri Lanka (41.2%), Taiwan (38.7%), Singapore (23.1%), Indonesia (21.0%), China (9.8%), Malaysia (9.0%), and India (3.8%). Serotypes 23F and 19F were the most common. Pulsed-field gel electrophoresis (PFGE) of 154 isolates from Asian countries showed several major PFGE patterns. The serotype 23F Spanish clone shared the same PFGE pattern with strains from Korea, Japan, Singapore, Taiwan, Thailand, and Malaysia. Fingerprinting analysis of pbp1a, pbp2x, and pbp2b genes of 12 strains from six countries also showed identical fingerprints of penicillin-binding protein genes in most strains. These data suggest the possible introduction and spread of international epidemic clones into Asian countries and the increasing problems of pneumococcal drug resistance in Asian countries for the first time.

Aminoacyltransferases↗