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Biomedical subjects

C H Chiu

Publications and source records attributed to C H Chiu.

At least 73 records · Page 4Linked to original sources

Relationship of beta-catenin and Bcl-2 expression to sulindac-induced regression of intestinal tumors in Min mice.

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause regression of early intestinal tumors and although this is believed to involve cyclooxygenase-2 and apoptosis, the molecular mechanisms remain unclear. Cytoplasmic and nuclear beta-catenin are overexpressed in many of these lesions and Bcl-2, which inhibits apoptosis, may also be elevated during the course of intestinal tumorigenesis. We recently showed that sulindac causes regression of 70-80% of small intestinal tumors in Min/+ mice within 4 days, but does not have the same impact on colonic lesions; after 20 days of treatment the tumor load stabilizes at 10-20% of that in untreated animals. The aim of this study was to determine if NSAID-induced regression of intestinal adenomas might be associated with changes in beta-catenin or Bcl-2 expression. Intestinal tumors from Min/+ mice were harvested after treatment with sulindac for 2, 4 or 20 days and evaluated for expression of beta-catenin and Bcl-2 using immunohistochemistry. There was a > or = 50% decrease in beta-catenin (P = 0.001) and diminishing Bcl-2 (P = 0.019) in small intestinal tumors harvested between 2 and 4 days of treatment when compared with untreated controls. In contrast, small intestinal tumors from animals treated for 20 days were not significantly different from untreated controls. Colonic tumors expressed higher levels of Bcl-2 than those from the small intestine and did not show any significant changes in either Bcl-2 or beta-catenin expression after treatment. Results suggest that modulation of aberrant beta-catenin expression occurs during NSAID-induced regression of intestinal adenomas and that Bcl-2 may confer resistance to these effects.

Adenoma↗

Prevalence of the virulence plasmids of nontyphoid Salmonella in the serovars isolated from humans and their association with bacteremia.

To determine if the virulence plasmid is one of the elements contributing to Salmonella bacteremia in humans, 436 clinical Salmonella isolates of different serovars were examined by a specific multiplex polymerase chain reaction assay for the presence of a virulence plasmid. These serovars showed differences in their ability to produce particular disease syndrome in humans. In the serovars usually causing bacteremia without concomitant gastroenteritis (primary bacteremia), i.e., S. choleraesuis, S. dublin, and S. enteritidis in this study, the rate of virulence plasmid carriage was 100%, while among those occasionally generating bacteremia following an episode of gastroenteritis (secondary bacteremia), the majority were plasmidless. Only a portion of S. typhimurium strains harbored a virulence plasmid; however, the rates of virulence plasmid carriage in S. typhimurium were not statistically different between non-fecal and fecal isolates (90% vs. 85%, 0.1 < P < 0.9). These results indicate that the virulence plasmids may be important for primary bacteremia, but not secondary bacteremia, to occur.

Bacteremia↗

Intracellular Salmonella typhimurium induce lysis of human polymorphonuclear leukocytes which is not associated with the Salmonella virulence plasmid.

The interaction between Salmonella typhimurium and human polymorphonuclear leukocytes (PMNs) was analyzed in vitro. Three S. typhimurium strains, the wild-type strain OU5043, its isogenic virulence plasmid-cured strain OU5048, and LT2, which represented the types that exhibited three mouse virulence levels, respectively, were used in this study. There was no correlation between the recovery of intracellular S. typhimurium from PMNs and the presence or absence of the virulence plasmid, or the strains' mouse virulence level. When the oxygen-dependent response of PMNs upon phagocytosis of S. typhimurium was examined by checking the intracellular reduction of nitroblue tetrazolium (NBT), the fraction of PMNs that reduced NBT on phagocytosis of the three strains was around 80%, whereas it was 58% with Escherichia coli, 95% with phorbol 12-myristate 13-acetate and 15% with a negative control. Thus there were no significant differences among the three Salmonella strains in terms of their ability to induce the oxidative response in PMNs. Microscopic analysis of Salmonella-infected PMNs indicated that the intracellular Salmonella induced lysis of PMNs. Both OU5043 and OU5048 exhibited a significant intracellular cytotoxic effect on PMNs after 24 hr of infection and this effect was not associated with the presence or absence of the virulence plasmid. On the other hand, lysis of PMNs was related to the intracellular survival of Salmnonella, as ofloxacin, an antibiotic, appeared to be able to protect human PMNs from Salmonella-induced cytotoxicity when this agent was added into the medium to inactivate the intracellular organism. The ability to induce lysis of PMNs by either wild-type or plasmid-cured strains of S. typhimurium may play a crucial role in the pathogenesis of non-typhoid Salmonella. The contribution of pSTV to human salmonellosis is likely to be limited. Furthermore, early institution of antibiotics with a high intracellular activity against Salmonella, such as fluoroquinolones, may be useful to prevent the dissemination of Salmonella infection.

Adult↗

Amino acid residues involved in the functional integrity of Escherichia coli methionine aminopeptidase.

Amino acid residues in the metal-binding and putative substrate-binding sites of Escherichia coli methionine aminopeptidase (MAP) were mutated, and their effects on the function of the enzyme were investigated. Substitution of any amino acid residue at the metal-binding site resulted in complete loss of the two cobalt ions bound to the protein and diminished the enzyme activity. However, only Cys70 and Trp221 at the putative substrate-binding site are involved in the catalytic activity of MAP. Changing either of them caused partial loss of enzyme activity, while mutations at both positions abolished MAP function. Both residues are found to be conserved in type I but not type II MAPs.

Amino Acid Substitution↗

Colour Doppler ultrasonography of retropharyngeal abscess.

OBJECTIVE: This study was conducted to determine the capability of colour Doppler ultrasonography (CDU) in evaluating retropharyngeal abscess in children. MATERIALS AND METHODS: From July 1996 to February 1998, five children with clinical suspicion of retropharyngeal abscess were evaluated by CDU. The distance from internal carotid artery (ICA) to cervical vertebra (CV) (DICA-CV) at the upper cervical level was measured by longitudinal ultrasonography. Fifty healthy children, aged from 1 to 15 years, were recruited in the study to measure DICA-CV as control. Colour Doppler ultrasonography was used to differentiate abscess from other pathology and to detect carotid sheath invasion. Computed tomography was performed to confirm the sonographic diagnosis. Measurements of the DICA-CV at regular intervals were performed to monitor the progression of retropharyngeal abscess. RESULTS: Retropharyngeal abscess was highly suspected in all cases under sonographic studies. A patient was found to have carotid sheath invasion. Computed tomography confirmed the diagnosis of retropharyngeal abscess in all cases. Retropharyngeal abscess can be evaluated by the measured DICA-CV. The DICA-CV decreased as the retropharyngeal abscess gradually resolved. CONCLUSION: Colour Doppler ultrasonography offers a sensitive method to evaluate retropharyngeal abscess in children. It can also be used to monitor the progression of retropharyngeal abscess and avoid unnecessary radiologic examinations.

Adolescent↗

Assessment of the arachidonic acid content in foods commonly consumed in the American diet.

Arachidonic acid (AA) is an extremely important fatty acid involved in cell regulation. When provided in the diet, it is cogently incorporated in membrane phospholipids and enhances eicosanoid biosynthesis in vivo and in vitro; however, controversy exists as to the levels of AA in food and in the diet. This study determined the amount of AA in cooked and raw portions of beef (rib eye), chicken (breast and thigh), eggs, pork (loin), turkey (breast), and tuna; it compared these results to values published in Agriculture Handbook No. 8 (HB-8). The cooked portions were prepared as described in HB-8. With the exception of chicken thigh and tuna, the levels of AA (w/w) in the selected foods analyzed were significantly higher, in general, than those values published in HB-8. The greatest differences were observed in beef (raw and cooked), turkey breast (raw and cooked), and pork (cooked) where AA levels were twice that of the values in HB-8. In contrast, the AA and n-3 fatty acid contents in tuna were almost half the HB-8 values. The present data indicate that HB-8 tends to underreport the amounts of AA in a number of foods commonly consumed in the American diet, and new initiatives should be considered to validate and update the current database for fatty acid composition of foods.

Arachidonic Acid↗

Antimicrobial susceptibilities of Campylobacter jejuni and coli by using E-test in Taiwan.

To report the in vitro antibiotic susceptibility of Campylobacter species, we determined the MICs of 6 antibiotics by E-test for 93 human clinical strains and 35 chicken strains. The 6 antimicrobial agents tested were gentamicin, erythromycin, clindamycin, tetracycline, ciprofloxacin, and nalidixic acid. Isolates from humans were significantly more susceptible than chicken strains to erythromycin, clindamycin and ciprofloxacin. Nearly all of the human and chicken strains were susceptible to gentamicin. Among human isolates of C. jejuni, cross-resistance between nalidixic acid and ciprofloxacin was found in 66% of the strains, but none of the nalidixic acid-susceptible strains was resistant to ciprofloxacin. The higher prevalence of ciprofloxacin resistance in this area may be attributable to the large amount use of quinolones in poultry. Because of the high resistance rates of chicken isolates to the commonly used antimicrobial agents, it is necessary to create innovative methods to limit the inappropriate use of antibiotics in poultry in order to prevent the spread of the drug-resistant strains to humans.

Animals↗

Hypothermia predisposing to Pseudomonas putida sepsis in a child with panhypopituitarism.

A 14-year-old boy presented with a 1-week history of hypothermia and obtundation. His medical history included surgical resection of craniopharyngioma with postoperative visual impairment and panhypopituitarism. The patient's rectal temperature remained persistently lower than 35 degrees C during the first 3 days of hospitalization. His blood pressure was 90/56 mmHg on admission. The peripheral blood leukocyte count was 2.7 x 10(10)/L with 18% neutrophils, 19% band forms, 44% metamyelocytes, 3% myelocytes, and 16% lymphocytes. The C-reactive protein concentration was 133.9 mg/L. Two separate blood cultures both yielded Pseudomonas putida. The patient was treated with amikacin and ceftazidime along with aggressive fluid therapy. Replacement therapy directed at his hormonal deficiencies was initiated as soon as his hemodynamic status was stabilized. The patient responded well to therapy with a gradual rise in body temperature and improvement in general activity. A growth experiment carried out on the P. putida isolate showed that the bacteria grew more rapidly at 30 degrees C than at 37 degrees C. The clinical course of the patient, as well as the results of the laboratory study, suggest that hypothermia may predispose human infection with P. putida.

Adolescent↗

Dynamics of regulatory evolution in primate beta-globin gene clusters: cis-mediated acquisition of simian gamma fetal expression patterns.

Phylogenetic reconstructions by parsimony were carried out on an enlarged body of primate gamma1 and gamma2-globin sequences. The results confirm that gamma1 and gamma2 arose from a tandem duplication in an ancient simian lineage ancestral to both platyrrhines (New World monkeys) and catarrhines (Old World monkeys and hominoids). Gene conversions between the two gamma homologs were frequent over the gamma gene proper but less frequent over the 5' flanking and very infrequent over the 3' flanking regions. The ancient platyrrhine conversion in the most distal 5' flanking region had the polarity of gamma2-->gamma1. Recent platyrrhine conversions between 5' regulatory sequences were very infrequent, in striking contrast to catarrhines which have large, uninterrupted stretches of converted 5' regulatory sequences. Comparisons of reconstructed ancestral primate and simian gamma promoter sequences revealed an accumulation of 21 nucleotide substitutions concentrated in or near cis-elements that may have mediated the change from embryonic to fetal gamma expression. Almost all 21 substitutions were retained in the lineages leading to functional gamma genes of extant catarrhines (both gamma1 and gamma2) and platyrrhines (most often gamma2). Fewer of these simian specific substitutions were retained in the platyrrhine gamma1 genes and new mutations occurred more often in the platyrrhine gamma1 than gamma2 promoters.

Animals↗

Sulindac causes rapid regression of preexisting tumors in Min/+ mice independent of prostaglandin biosynthesis.

Several lines of evidence strongly link prostaglandins (PGs) and leukotrienes (LTs) to cancer of the intestine. Several studies have reported a 40-50% reduction in mortality from colorectal cancer in individuals who routinely consume nonsteroidal anti-inflammatory drugs, possibly by inhibiting cyclooxygenase activity. However, the role of eicosanoids in this process is still unclear. The heterozygote Min/+ mouse model, like patients with familial adenomatous polyposis, carries a nonsense mutation in the adenomatous polyposis coli (APC) gene that results in the spontaneous development of intestinal adenomas (100% incidence). This study investigated the association between eicosanoid biosynthesis, intestinal tumor load, and the chemotherapeutic effect of the nonsteroidal anti-inflammatory drug sulindac during early and preexisting phases of tumor growth and development as well as residual effects after drug withdrawal. Administration of sulindac (320 ppm) to Min/+ mice reduced the tumor number by 95% but did not alter the levels of PGE2 and LTB4 in intestinal tissues. Increasing PGE2 and LTB4 levels by 44% with dietary arachidonic acid supplementation had no effect on tumor number or size. When sulindac was added to the arachidonic acid-supplemented diet, tumor number was reduced by 82%, whereas eicosanoid levels remained elevated. In Min/+ mice with established tumors, treatment with sulindac for 4 days reduced tumor number by 75%, and continual administration of sulindac was necessary to maintain a reduced tumor load. In summary, alterations in eicosanoid formation were not correlated with tumor number or size in the Min/+ mouse model; thus, the antitumor effect of sulindac seems to be PG independent.

Adenomatous Polyposis Coli↗

Identification of febrile neonates unlikely to have bacterial infections.

OBJECTIVE: A prospective study was undertaken to evaluate the usefulness of low risk criteria for identifying febrile neonates unlikely to have bacterial infections, particularly bacteremia and meningitis. Using these criteria we wished to check whether these low risk neonates can be safely managed as inpatients under close observation but without receiving empiric antibiotic therapy. STUDY DESIGN: We conducted a prospective study of 250 consecutive infants 28 days of age or less (range, 4 to 28 days) who had rectal temperatures of at least 38 degrees C. After a complete history, physical examination and sepsis workup, the 131 febrile neonates with clinical and laboratory findings indicating low risk for bacterial infections were hospitalized, closely observed and not given antibiotics. The low risk criteria used to identify these neonates included well appearance; absence of physical signs of an ear, eye or soft tissue infection; a white blood cell count of 5000 to 15,000/mm3, a neutrophil band form count of < 1500/mm3, a spun urine specimen that had < 10 white blood cells per high power field on microscopy and a C-reactive protein value of < 20 mg/l. The remaining 119 febrile neonates who did not meet the low risk criteria were hospitalized and given empiric antibiotics pending culture results. RESULTS: The overall incidence of bacterial infections in the 250 febrile neonates was 16.4% (41 neonates) with bacteremia and/or meningitis occurring in 4.4% (11 neonates). Of the 131 low risk neonates only one (0.8%) had a bacterial infection (urinary tract infection) compared with 40 (33.6%) among the 119 who did not meet the criteria (P < 0.05). The negative predictive value of these criteria for excluding bacterial infections was 99.2% (95% confidence interval, 97.7% to 100%). For bacteremia and meningitis this figure became 100%. However, the positive predictive value and specificity of the criteria were too low to identify all febrile neonates with bacterial infections. Among the low risk group 58 (44.3%) were reclassified on the second or third hospital day, because of continued fever (35), poor activity (14) and white blood cell count > 15000/mm3 on a repeat blood test (9). They were given antibiotics, but only 1 had a urinary tract infection. This patient was then treated with a 7-day course of antibiotics. All low risk neonates recovered uneventfully with no relapses observed during their hospital stay or at the time of minimum 1-week outpatient follow-up visits. CONCLUSION: By the low risk criteria a substantial number of febrile neonates at low risk for bacterial infections can be identified and managed safely as inpatients without antibiotic therapy.

Anti-Bacterial Agents↗

A pilot study of seven days of ceftriaxone therapy for children with Salmonella enterocolitis.

BACKGROUND: The most effective therapy for non-typhoid Salmonella enterocolitis is still unknown. Traditionally, unless extraintestinal complications are present, antimicrobial drugs are not recommended, since earlier trials have shown that antibiotics such as ampicillin, chloramphenicol, or co-trimoxazole, do not shorten the duration of diarrhea and may even prolong convalescent fecal carriage of the bacteria. However, the recently-developed third generation cephalosporin ceftriaxone has been used successfully in the treatment of typhoid fever and other systemic salmonellosis. A controlled, pilot study was therefore undertaken to evaluate the efficacy of intravenous ceftriaxone in the treatment of children with non-typhoid Salmonella enterocolitis. METHODS: Fifteen children with Salmonella enterocolitis and bacteremia who were eligible for antibiotic therapy were given ceftriaxone intravenously for 7 days and 15 children with enterocolitis but without bacteremia who were admitted for supportive treatment during the study period were selected as the control group. Available stool samples collected on days, 7, 14, and 30 after the completion of the drug therapy were checked for the presence of the bacteria using polymerase chain reaction (PCR) and culture methods. RESULTS: The result showed that the duration of diarrhea was not significantly affected by ceftriaxone treatment. However, the difference in the rate of clearance of Salmonella from stools, as defined by negative stool cultures and PCR, was statistically significant between the two groups on posttreatment days 7 and 14. Only one patient given ceftriaxone was shown to have recrudescence of the bacteria in feces on day 14. One month after therapy, PCR was positive in two of the ten cases tested and one of these two experienced a relapse of diarrhea, whereas bacterial carriage was maintained in 63% of the control patients. CONCLUSION: A prompt eradication of Salmonella in feces was observed in most of the patients treated with ceftriaxone in this study. If further studies confirm the efficacy of this therapy and the risk of inducing drug resistance is minimal, the epidemiologic problem created by convalescent fecal bacterial carriage may justify a short-course of ceftriaxone therapy for children with Salmonella enterocolitis.

Ceftriaxone↗

Salmonella typhimurium brain abscess in a six-month-old infant: a case report and review of the literature.

We report the case of a six-month-old male infant with brain abscess caused by Salmonella typhimurium. Upon admission, he was suffering from fever, diarrhea, drowsiness and convulsion. Salmonella meningitis was identified by CSF examination. Following failure of antibiotic therapy to control his fever, brain computerized tomography (CT) was ordered 5 days later and revealed a brain abscess. He received surgical excision of the abscess and recovered completely after receiving ceftriaxone therapy for 8 weeks. The case of our patient, together with 11 cases of Salmonella brain abscess from the English literature are reviewed. There was a male preponderance among these patients (male: female = 2.67 : 1) and the majority were less than one year old. Salmonella typhimurium, typhi, and enteritidis occurred most frequently. Fever, seizure, signs and symptoms of increased intracranial pressure and change in mental status were the most common clinical features. Purulent meningitis was a major predisposing factor. Successful treatment was associated with early identification, prompt surgical intervention, high dose, long-term antibiotic therapy, and close follow-up for possible recurrence and to determine the presence of neurological sequelae.

Anti-Bacterial Agents↗

Reduction of two functional gamma-globin genes to one: an evolutionary trend in New World monkeys (infraorder Platyrrhini).

Nucleotide sequences were determined for the gamma1- and gamma2-globin loci from representatives of the seven anciently separated clades in the three extant platyrrhine families (Atelidae, Pitheciidae, and Cebidae). These sequences revealed an evolutionary trend in New World monkeys either to inactivate the gamma1 gene or to fuse it with the gamma2 gene, i.e. to have only one functional fetally expressed gamma gene. This trend is clearly evident in six of the seven clades: (i) it occurred in atelids by deletion of most of the gamma1 gene in the basal ancestor of this clade; (ii-iv) in pitheciid titi, saki, and cebid capuchin monkeys by potentially debilitating nucleotide substitutions in the proximal CCAAT box of the gamma1 promoters and (v and vi) in cebid owl and squirrel monkeys by crossovers that fused 5' sequence from gamma1 with 3' sequence from gamma2. In the five clades with gamma1 and gamma2 loci separated by intergenic sequences (the fifth clade being the cebid marmosets), the gamma2 genes retained an unaltered proximal CCAAT motif and their gamma2 promoters accumulated fewer nucleotide substitutions than did the gamma1 promoters. Thus, phylogenetic considerations indicate that the stem platyrrhines, ancestral to all New World monkeys, had gamma2 as the primary fetally expressed gamma gene. A further inference is that when the earlier stem anthropoid gamma gene duplicated, gamma2 (at its greater downstream distance from epsilon) could evade embryonic activation by the locus control region but could be fetally activated once released by regulatory mutations from fetal repressors.

Animals↗

Clinical and microbiological analysis of six children with acute suppurative parotitis.

Six children including two neonates with acute suppurative parotitis are described. They presented typical symptoms and signs of fever (4/6) and swelling (6/6), tenderness (6/6), erythema (4/6) and local warmness (4/6) of the parotid gland affected. Leucocytosis and an elevated erythrocyte sedimentation rate and serum amylase level may be seen. The presence of purulent discharge from the Stensen duct when the parotid gland is externally compressed is pathognomonic of the disease, and the microbiological diagnosis can be made by culture of the pus. Microbiologically, this series highlights the polymicrobic nature and importance of Streptococcus viridans in paediatric suppurative parotitis, indicating, therefore, that the causative bacteria entered the gland from the oral cavity. Our data also suggest that initial antibiotic therapy for such patients should provide adequate coverage for streptococci and staphylococci as well as for anaerobic bacteria.

Acute Disease↗