PubMed Health⌕ Search

Biomedical subjects

S C Chang

Publications and source records attributed to S C Chang.

At least 199 records · Page 11Linked to original sources

Two related potent antiviral compounds: 3-bromo-N-butyl-4-butylamino-1,8-naphthalenedicarboximide (1) and 4-amino-3-bromo-N-butyl-1,8-naphthalenedicarboximide (2).

The crystal structures of two brominated derivatives of 4-amino-N-butyl-1,8-naphthalenedicarboximide [alternative systematic names: 8-bromo-2-butyl-7-butylamino-1H-benzo[de]isoquinoline-1,3(2H)-dione, C20H23BrN2O2, and 7-amino-8-bromo-2-butyl-1H-benzo[de]isoquinoline-1,3(2H)-dione, C16H15BrN2O2] are reported. The N-butyl groups, which are common to both compounds, are perpendicular to the plane of the naphthalenedicarboximide ring system. The butylamino group at position 4 in (1) is in the plane of the naphthalenedicarboximide ring, with the butyl group oriented towards the peri position of the naphthalenedicarboximide ring. This arrangement results in an opening of the (ring C)-N-(butyl C) angle.

Antiviral Agents↗

Cellular proteins specifically bind to the 5'-noncoding region of hepatitis C virus RNA.

Hepatitis C virus (HCV) RNA contains a highly conserved 5'-noncoding region (5'NCR) which may be important in viral multiplication. To study the possible mechanisms of the cellular proteins involved in HCV replication and pathogenesis, a gel mobility shift assay and competition analysis were performed with the HCV 5'NCR. Two specific complexes were formed between the 341-nucleotide RNA of the HCV 5'NCR and proteins of mammalian cells. The specific RNA-protein complexes were maintained in the region of the 5'NCR from nucleotides 131 to 253. Nevertheless, the slower migrating RNA-protein complex failed to form when a polypyrimidine tract sequence (191-UCCUUUCUU-199) in the stem-loop III structure of HCV 5'NCR was changed to 191-UCCUUUggU-199. A uv cross-linking assay further identified two cellular proteins, p87 and p120, that specifically bound to the stem-loop III structure. Mutations at the polypyrimidine tract sequence inhibited the binding of p87, but maintained the ability of the mutant HCV RNA to interact with p120. Translation competition assay demonstrated that the 5'NCR from nt 131 to 253 within the stem-loop III structure is important for the translation of HCV core protein. In addition, p120 and unidentified cellular proteins are likely to be involved in the translation of HCV polyprotein, whereas p87 may play important roles in HCV multiplication other than translation.

Animals↗

Identification of a satellite double-stranded RNA in the parasitic protozoan Trichomonas vaginalis infected with T. vaginalis virus T1.

Co-infection by a 0.5-kb small double-stranded (ds) RNA together with Trichomonas vaginalis virus (TVV) genomic 4.6-kb dsRNA is commonly observed in a number of T. vaginalis isolates. By molecular cloning and primer extension experiments, the 497-bp cDNA sequence of a 0.5-kb dsRNA co-infecting with TVV-T1 in T vagina/is T1 isolate was elucidated. Consistent with the replication cycle of a typical dsRNA virus, a plus-strand viral RNA beginning at +1 of the 0.5-kb dsRNA was identified in infected T. vaginalis T1 cells by primer extension and Northern hybridization studies. The 0.5-kb dsRNA was separately encased in TVV capsids from the viral genomic dsRNA, as shown by protein analysis and electron microscopic examination of viral particles purified by multiple rounds of CsCl gradient centrifugation. The riboprobes transcribed from a cloned cDNA of the 0.5-kb dsRNA exhibited strong hybridization to a small dsRNA in a T vaginalis T9 isolate, which harbors a TVV-T9 distantly related to TVV-T1, but the same probes showed very little hybridization to the viral genomic dsRNA of both TVV-T1 and TVV-T9. Very little sequence homology between the 0.5-kb dsRNA and the 4.6-kb dsRNA in TVV-T1 was found by computer-assisted analysis, suggesting that the small dsRNA in T. vaginalis T1 is not derived from the genome of TVV-T1 or other distantly related T. vaginalis viruses. These results suggest that the small dsRNAs in T vaginalis are satellite RNAs of T. vaginalis virus.

Animals↗

Influence of beta-lactamase inhibitors on the activity of oxacillin against methicillin-resistant Staphylococcus aureus.

We studied the in vitro susceptibility to oxacillin of 46 isolates of methicillin-resistant Staphylococcus aureus (MRSA) isolates with a minimum inhibitory concentration (MIC) > 8 micrograms/ml of oxacillin, with and without adding clavulanic acid, sulbactam, or tazobactam in three different concentrations (2, 4, and 8 micrograms/ml). All 46 strains were found by the rapid chromogenic cephalosporin method to be beta-lactamase producers. For those strains with low-level resistance (MIC of 16 or 32 micrograms/ml), the MICs of oxacillin decreased four- to 32-fold and two- to 32-fold after adding sulbactam and tazobactam, respectively. For those with high-level resistance (MIC of > or = 64 micrograms/ml), the MICs either did not change or decreased only two-fold after we added one of three beta-lactamase inhibitors. The results suggest that beta-lactamase production probably plays a role in resistance to oxacillin in those MRSA strains of low-level oxacillin resistance.

Anti-Bacterial Agents↗

In vitro activities of antimicrobial agents, alone and in combination, against Acinetobacter baumannii isolated from blood.

In vitro activities of 15 antimicrobial agents against 90 strains of Acinetobacter baumannii isolated from blood cultures from hospitalized patients were determined using the agar dilution method. Imipenem, ofloxacin, and ciprofloxacin had the best antimicrobial activity with minimum inhibitory concentrations (MIC50s) of 0.25 mu g/ml and MIC90s of 0.5-1 mu g/ml. beta-lactam antibiotics other than imipenem had poor activity, with MIC50s ranging from 8 to 64 mu g/ml and MIC90s from 32 to > or = 256 mu g/ml. The checkerboard titration method was used to study the effects of combination of two antimicrobial agents. Combinations of ceftazidime, aztreonam, imipenem, or ciprofloxacin with amikacin showed either synergistic effects or partial synergistic effects for 40.9%-86.4% of 22 tested strains. The best in vitro activity was observed with the combination of imipenem and amikacin. No antagonistic effects were observed with the combination of imipenem and amikacin. Synergistic effects were confirmed by time-kill curve studies. In conclusion, imipenem, ofloxacin, and ciprofloxacin were the three most active agents against human blood isolates of A. baumannii. The combination of a beta-lactam or ciprofloxacin with amikacin was synergistic for some of the isolates.

Acinetobacter↗

Polymicrobial bacterial pericarditis with mediastinitis after endotracheal intubation.

Polymicrobial bacterial pericarditis with mediastinitis after traumatic endotracheal intubation is an unusual condition. We report a 54-year-old man, a victim of nasopharyngeal carcinoma, who developed pericardial effusion with tamponade after traumatic endotracheal intubation. The diagnosis of polymicrobial bacterial pericarditis was made when pericardiocentesis revealed purulent fluid that grew a mixed culture of anaerobic and aerobic bacteria, reflecting the normal upper airway flora. By bronchoscopic study, a laceration over the lower trachea was detected. The patient received prolonged aggressive antibiotic therapy and pericardial drainage. The infection improved, but the patient later died from another episode of nosocomial infection.

Anti-Bacterial Agents↗

Macrolides resistance of common bacteria isolated from Taiwan.

To determine the susceptibility to macrolides of common pathogenic bacteria isolated from Taiwan, the in vitro activities of erythromycin, roxithromycin, azithromycin, clarithromycin, and dirithromycin were tested against 492 clinical isolates of eight different bacteria, collected from the National Taiwan University Hospital. The results showed high minimum inhibitory concentrations (MICs) against most of the tested bacteria. The MIC90s for Staphylococcus aureus (both methicillin-resistant and -sensitive strains), coagulase-negative staphylococci (both methicillin-resistant and -sensitive strains), Streptococcus pyogenes, Streptococcus pneumoniae, enterococci, peptostreptococci, and Bacteroides fragilis were all > or = 256 micrograms/ml. The MIC50s for methicillin-resistant strains of S. aureus and coagulase-negative staphylococci, and enterococci were > or = 256 micrograms/ml. For S. pneumoniae, peptostreptococci, and B. fragilis, the MIC50s were > 8 micrograms/ml. The resistance rates to macrolides were 80% or more in methicillin-resistant staphylococci and about 30% in methicillin-sensitive staphylococci. Around 55% of S. pneumoniae strains and 37 approximately 42% of S. pyogenes strains were resistant to macrolides. Cross-resistance to different macrolides was clearly demonstrated in most of the resistant strains.

Anti-Bacterial Agents↗

Survey of knowledge, attitudes and practices for tuberculosis among general practitioners.

SETTING: Representative sample survey of knowledge, attitudes and practices (KAP) for tuberculosis among private general practitioners (GPs) in 1993 in Korea, OBJECTIVE: To investigate the KAP of general practitioners on the prevention and treatment of tuberculosis. DESIGN: Questionnaire surveys were performed for 923 private general practitioners through 29 health centres. RESULTS: 49% of GPs considered that the Korean tuberculosis situation is not serious. 54% were worried about infection from patients. 47% answered that BCG vaccination causes untoward reactions with no or limited effectiveness. 47% considered the National Tuberculosis Programme (NTP) unfavourably. Over 50% did not consider sputum examination essential in case finding/diagnosis, and 75% in monitoring of treatment response. For initial treatment of active tuberculosis, only 11% were prescribing the current Korean NTP's six-month standard regimen. 73% were giving currently non-recommendable regimens, and 16% unacceptably bad regimens. However, this situation could be improved, as 80% of GPs expressed the wish to acquire knowledge. CONCLUSION: Many misunderstandings were found in the field of transmission, BCG vaccination and the performance of the NTP; sputum examinations were considerably neglected in case finding/diagnosis and treatment monitoring. As for treatment, 89% were giving either non-recommendable regimens or bad regimens.

Adult↗

Genetic diagnosis of haemophilia A of Chinese origin.

Genetic diagnosis of haemophilia A has been studied in two aspects. One is to directly identify the mutations in the factor VIII genes of the affected probands, and the other is to examine the usefulness of several intragenic factor VIII markers for gene tracking. Direct mutational analysis by PCR-SSCP (polymerase chain reaction--single-strand conformation polymorphism) has been accomplished previously in 87 haemophilia A patients, accounting for nearly 10% of cases in Taiwan. Of the 87 cases, 46% were with point mutations, short deletions or insertions, and most of the remaining were with gene inversion readily identified by Southern blotting. Further examination of 112 patients has estimated a 33% incidence for gene inversion in all the patients with haemophilia A, or 37% in severe cases. Since the direct mutational detection described above cannot be used in all Chinese families with haemophilia A, genetic markers were also investigated. The two CA repeat markers located at intron 13 (CA-13) and intron 22 (CA-22), respectively, were amplified and analysed simultaneously. Seven different alleles with 18-24 CAs have been identified for CA-13. Alleles of 20 and 21 CAs are the most common and their population frequency was 0.68 and 0.24, respectively. The CA-22 marker contained a repetition of (GT)n(AG)n as was identified in the white European but not in the Canadian population. Alleles with 25 and 26 GT/AGs account for 18% and 75% of this group of samples, respectively. The expected rate of heterozygosity for either CA markers was 68%, although a value of 57% was observed by haplotype analysis, indicating an association of the two repeat markers. Nevertheless, the study of 62 females showed that with the combined use of CA-13 and CA-22 with BclI, approximately 71% would be informative for these markers. This number may increase to 81% if XbaI polymorphism is added. We propose that a better genetic diagnosis procedure for Chinese individuals would be first to look for the inversion mutation, secondly for one of the intragenic markers, and then at the PCR-SSCP analysis.

Blotting, Southern↗

Functional domains of delta antigens and viral RNA required for RNA packaging of hepatitis delta virus.

The functions of delta antigens (HDAgs) in the morphogenesis of hepatitis delta virus (HDV) have been studied previously. The C terminus of large HDAg has been shown to complex with the small surface antigen (HBsAg) of helper hepatitis B virus, whereas the assembly of small HDAg requires interaction with the N terminus of large HDAg (M.-F. Chang, C.-J. Chen, and S. C. Chang, J. Virol. 68:646-653, 1994). To further examine the molecular mechanisms by which HDAgs are involved in the assembly of HDV RNA, we have cotransfected Huh-7 cells with plasmids representing a longer than unit-length HDV and the small HBsAg cDNAs. We found that HDAg mRNA could be generated from an endogenous promoter within the HDV cDNA that was translated into large HDAg. Large HDAg is capable of complexing with monomeric HDV genomic RNA to form ribonucleoprotein particles (RNPs) and is capable of forming enveloped HDV-like particles in the presence of small HBsAg without undergoing HDV replication. In addition, the middle region from amino acid residues 89 to 145 of large HDAg is required for assembly of the RNPs but is dispensable for assembly of the enveloped particles. RNA assembly is also demonstrated with small HDAg when it is cotransfected with a packaging-defective large HDAg mutant and small HBsAg. Leu-115 within the putative helix-loop-helix structure of the small HDAg is important for the replication of HDV but is not essential for RNA assembly, suggesting that conformational requirements of small HDAg for replication and assembly of viral RNA may be different. Further studies indicate that a 312-nucleotide linear HDV RNA from one end of the HDV and structure is sufficient to form RNP complexes competent for assembly of virus-like particles with large HDAg and small HBsAg.

Antigens, Viral↗

Effects of ascites and body position on gas exchange in patients with cirrhosis.

The effects of ascites and body position on gas exchange were evaluated in 22 male cirrhotics. All underwent spirometry and plethysmography in the sitting (erect) position. Single breath carbon monoxide diffusing capacity (DLco) was measured in the erect and supine positions in a random sequence. A significantly negative correlation was found between Kco (DLco corrected by alveolar volume [VA]) and lung volumes. DLco was significantly higher in the erect than in the supine position. On the other hand, Kco was significantly higher in the supine position. The differences of DLco and Kco between the erect and supine positions (the data in the supine minus those in the erect position) correlated highly with FEV1 and FVC. Thirteen patients underwent large volume paracentesis, and pulmonary function tests were done one day before and after paracentesis. Lung volumes and DLco increased significantly after paracentesis. In contrast, Kco decreased significantly. A significantly negative correlation was found between the change of Kco before and after paracentesis and that of lung volumes (the data after minus those before paracentesis). There was no remarkable change in the differences of DLco and Kco between the two positions after paracentesis. It is concluded that ascites may prevent further worsening of gas exchange and attenuate the postural effect on gas exchange in cirrhotic patients with significant amounts of ascites.

Adult↗

Trichosporon beigelii fungemia in patients with acute leukemia: report of three cases.

Trichosporon beigelii fungemia with localized visceral involvement or dissemination is a life-threatening infection in patients with granulocytopenia. We report three cases of T. beigelii fungemia in patients with acute leukemia seen at the National Taiwan University Hospital. Two patients were in the granulocytopenic state after cytoreductive chemotherapy, while one was in complete remission. Fever persisted or recurred despite conventional antibiotic treatment when fungemia developed. Cutaneous trichosporonosis was noted in one patient, which was misdiagnosed as candidiasis. An indwelling catheter constituted the likely portal of entry in two patients. Therapeutic response to amphotericin B is generally not achieved in patients without recovery of neutrophil counts and in those with retained catheters.

Adolescent↗

In Vitro antimicrobial susceptibilities of Streptococcus pneumoniae isolated from two teaching hospitals in Taiwan, 1989-1995.

The susceptibility of 46 pneumococcal isolates collected during October 1989 to May 1995 from National Taiwan University Hospital and Taipei Municipal Yang Ming Hospital was studied. Among these isolates, the resistant rate of penicillin G was 21.7%; the penicillin G-resistant strains were more frequently resistant than the penicillin-sensitive strains to other beta-lactam antimicrobial drugs. The minimum bactericidal concentrations (MBCs) of penicillin G for all isolates were equal to, or one dilution higher than, minimum inhibitory concentrations (MICs). Three strains were false positive for penicillin resistance among isolates of Streptococcus pneumoniae screened with oxacillin. On the other hand, resistance to penicillin G was often independent of resistance to erythromycin. Vancomycin was the most active agent tested.

Humans↗

[Secular trends in the etiology of nosocomial infection at a teaching hospital in Taiwan, 1981-1994].

Surveillance system of nosocomial infection was established in 1980 at the National Taiwan University Hospital (NTUH). To identify pathogens and the secular trends in the etiology of nosocomial infection from 1981 to 1994, the prospective, hospital-wide nosocomial surveillance data were analysed. During this period, 22,146 pathogens causing nosocomial infections were isolated. Gram-negative aerobic bacteria remained the major pathogens, but gram-positive cocci and fungi increased rapidly in the past 14 years. When the overall pathogen distribution is examined, Pseudomonas areuginosa was the most frequently isolated pathogen, but Candida albicans and other yeasts have taken the leading position since 1993. Staphylococcus aureus and coagulase-negative staphylococci also increase significantly in recent years. When the pathogens causing infection at the 4 major sites were examined. P. aeruginosa was the pathogen most often associated with respiratory tract and surgical wound infections. In blood stream and urinary tract infections, we observed Escherichia coli was replaced by C. albicans and other yeasts as a most common isolate in these years. In addition, C. albicans and other yeasts and methicillin-resistant S. aureus (MRSA) are emerging as major nosocomial pathogens at NTUH. C. albicans and other yeast increased from 1.8% in 1981 to 14.9% in 1994 in the overall nosocomial infection. The increase was found in the blood stream (2.1% to 16.2%) and urinary tract infections (5.4% to 24.7%). Of 1,742 nosocomial S. aureus isolates, the percentage of MRSA rose from 12.5% in 1981 to 55.2% in 1994. The high percentage of MRSA was observed at 4 major anatomic sites of infection. In summary, significant shifts in the pathogens of nosocomial infection have occurred in the past 14 years at NTUH, and the distribution of nosocomial pathogens was similar to those reported in the United States in recent years.

Bacteremia↗

Nuclear localization signals in the core protein of hepatitis C virus.

The core protein of the hepatitis C virus is derived from the N-terminal 191 amino acids of the viral polyprotein by proteolytic cleavage. In the current study, subcellular localizations of the HCV core and its beta-galactosidase fusion proteins in transfected cells were examined by indirect immunofluorescence and cytochemical staining. The core protein was located predominantly in the cytoplasm 6 days after a plasmid encoding the full-length core protein had been introduced into mammalian cells. A hydrophobic domain in the C-terminal region of the core protein may block the efficiency of nuclear transport, since a beta-galactosidase fusion protein that contains HCV core protein lacking the C-terminal 66-amino-acid was located within the nuclei of mammalian cells 24 hours posttransfection. Three independent nuclear localization signals were further identified in the N-terminal region of the HCV core protein.

Animals↗

Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development.

Partially purified extracts from newborn calf articular cartilage were found to induce cartilage and bone when subcutaneously implanted in rats. This activity showed characteristics of bone morphogenetic proteins (BMPs). Degenerate oligonucleotide primer sets derived from the highly conserved carboxyl-terminal region of the BMP family were designed and used in reverse transcription-polymerase chain reactions with poly(A)+ RNA from articular cartilage as template to determine which BMPs are produced by chondrocytes. Two novel members of the transforming growth factor-beta (TGF-beta) superfamily were identified and designated cartilage-derived morphogenetic protein-1 (CDMP-1) and -2 (CDMP-2). Their carboxyl-terminal TGF-beta domains are 82% identical, thus defining a novel subfamily most closely related to BMP-5, BMP-6, and osteogenic protein-1. Northern analyses showed that both genes are predominantly expressed in cartilaginous tissues. In situ hybridization and immunostaining of sections from human embryos showed that CDMP-1 was predominantly found at the stage of precartilaginous mesenchymal condensation and throughout the cartilaginous cores of the developing long bones, whereas CDMP-2 expression was restricted to the hypertrophic chondrocytes of ossifying long bone centers. Neither gene was detectable in the axial skeleton during human embryonic development. The cartilage-specific localization pattern of these novel TGF-beta superfamily members, which contrasts with the more ubiquitous presence of other BMP family members, suggests a potential role for these proteins in chondrocyte differentiation and growth of long bones.

Amino Acid Sequence↗

Usefulness of soluble interleukin 2 receptor in differentiating tuberculous and carcinomatous pleural effusions.

OBJECTIVE: To evaluate the usefulness of soluble interleukin 2 receptor (sIL-2R) in differentiating tuberculous and carcinomatous pleural effusions. METHODS: Levels of sIL-2R were measured simultaneously in plasma and pleural fluid in 111 patients with pleural effusions of unknown causes. RESULTS: The causes of pleural effusions were tuberculosis in 42 cases, carcinoma in 41 cases, pneumonia in 18 cases, and heart failure in 10 cases. In all groups of patients, sIL-2R levels were significantly higher in pleural fluid than in plasma. Plasma and effusion levels of sIL-2R were highest in the patients with tuberculosis, followed by those with carcinoma, pneumonia, and heart failure. Levels were significantly higher in the tuberculous group than in the carcinomatous group. To differentiate tuberculous from carcinomatous effusions, the highest plasma and effusion sIL-2R values obtained from the carcinomatous group were chosen as cutoff points (test specificity, 100%). The sensitivities of plasma and effusion sIL-2R levels in differentiating tuberculous and carcinomatous pleural effusions were 50% (21 of 42 samples) and 81% (34 of 42 samples), respectively. CONCLUSIONS: Although increased plasma and pleural fluid levels of sIL-2R should not be viewed as a diagnostic test specific for tuberculous pleural effusion, sIL-2R level appears to be clinically useful as a biochemical marker to differentiate tuberculous and carcinomatous pleural effusions.

Adult↗