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Biomedical subjects

Y S Lim

Publications and source records attributed to Y S Lim.

At least 37 records · Page 2Linked to original sources
PubMed1998

Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in MDR cells.

MDR1 promoter has been shown to contain heat shock elements (HSE), and it has been reported that FM3A/M and P388/M MDR cells show a constitutively activated heat shock factor (HSF), suggesting that HSF might be an important target for reversing the multidrug resistance. Therefore, it was examined whether quercetin, which has been shown to interfere with the formation of the complex between HSE and HSF, and to downregulate the level of HSF1, can sensitize MDR cells against anticancer drugs by inhibition of HSF DNA-binding activity. In this study, quercetin appeared to inhibit the constitutive HSF DNA-binding activity and the sodium arsenite-induced HSF DNA-binding activity in the MDR cells. The basal and sodium arsenite-induced MDRCAT activities were remarkably suppressed by the treatment of quercetin. These results were well consistent with the finding that the treatment of quercetin decreased the expression level of P-gp, MDR1 gene product, in dose-dependent manner, and markedly increased the sensitivity of MDR cells to vincristine or vinblastine. These results suggest that quercetin can decrease the expression of P-gp via inhibition of HSF DNA-binding activity, and might be useful as a chemosensitizer in MDR cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Vaccination with an ovalbumin/interleukin-4 fusion DNA efficiently induces Th2 cell-mediated immune responses in an ovalbumin-specific manner.

To more effectively drive immune responses toward antigen-specific T helper type 2 (Th2) cell-mediated responses, we constructed a mammalian expression vector (pOVA/IL4) carrying a fused gene in which the ovalbumin (OVA) cDNA was covalently linked to murine interleukin-4 (IL-4) cDNA. A biologically active OVA/IL4 protein was expressed by the transfected COS cells with the pOVA/IL4 DNA, as demonstrated by Western blotting and cytokine bioassay. Intramuscular injection of BALB/c mice with the pOVA/IL4 DNA increased both the production of OVA-specific IL-4 by CD4+ T cells and the ratio of anti-OVA IgG1 to anti-OVA IgG2a isotypes, while the injection with the pOVA DNA alone, or with the mixture of the pOVA and pIL4 DNA did no or little increase. Furthermore, the OVA-specific, Th2 cell-mediated immune responses were significantly enhanced by multiple injections with the pOVA/IL4 DNA. These studies indicate that the direct linkage of an OVA gene to an IL-4 gene in the expression plasmid confines the effects of IL-4 to the OVA-specific cells, efficiently driving the immune response toward OVA-specific, Th2 cell-mediated responses.

Animals↗
PubMed1998

Potentiation of antigen-specific, Th1 immune responses by multiple DNA vaccination with an ovalbumin/interferon-gamma hybrid construct.

The preferential differentiation of T helper (Th) cells to Th1 or Th2 subsets is important with respect to susceptibility or resistance to particular infections, or to autoimmune diseases and allergic diseases. To more effectively drive immune responses toward antigen-specific Th1 responses, we constructed a mammalian expression vector (pOVA/IFN-gamma) carrying a hybrid gene in which the ovalbumin (OVA) (a model antigen) cDNA was covalently linked to murine interferon-gamma (IFN-gamma) cDNA. Intramuscular injection of BALB/c mice with the pOVA/IFN-gamma DNA increased both the production of OVA-specific IFN-gamma by CD4+ T cells and the ratio of anti-OVA immunoglobulin G (IgG) 2a to IgG1 isotypes, while the injection with the pOVA alone, or with the mixture of the pOVA and pIFN-gamma, caused no or little increase. Furthermore, the OVA-specific, Th1 immune responses were dramatically augmented by multiple injections with the pOVA/IFN-gamma DNA. These studies indicate that the direct linkage of an OVA gene to an IFN-gamma gene in the expression plasmid is required for efficiently confining the Th1 effects of IFN-gamma to the OVA-specific cells, and the linkage effect of the OVA/IFN-gamma DNA can be potentiated by multiple vaccination.

Animals↗
PubMed1998

Purification and characterization of a novel levanoctaose-producing levanase from Pseudomonas strain K-52.

Levan-assimilating micro-organisms from soil samples were screened for levanoligosaccharide-generating enzyme production. The isolated strain K-52 produced an extracellular levanoctaose-generating enzyme and was identified as belonging to genus Pseudomonas. The levanase was purified to homogeneity by (NH4)2SO4 fractionation and successive column chromatography on DEAE-cellulose, phenyl-Toyopearl 650 M, Sephadex G-100 and hydroxyapatite. The molecular mass of the enzyme was estimated as approx. 38 kDa by both SDS/PAGE and gel filtration, and its isoelectric point was approx. pH 4.8. The optimum temperature and pH for the enzyme reaction were 35 and 7.0 respectively. The enzyme was stable at a pH range of 6.0-9.0 at 4 degrees C and up to 40 degrees C at pH 6.8. The enzyme activity was inhibited by Fe2+, Cu2+, Hg2+ and Ag2+. The levanase was specific toward 2,6-beta-D-fructosidic linkages of levan and did not hydrolyse other polysaccharides such as inulin and dextran. Chemical modification on the levanase suggested that cysteine and histidine residues are essential for enzyme activity. The levanoctaose liberated by levanase reaction was used selectively only by the intestinal beneficial micro-organisms, such as Bifidobacterium and Lactobacillus spp.

Bacterial Proteins↗
PubMed1997

Involvement of heat shock factor in regulating transcriptional activation of MDR1 gene in multidrug-resistant cells.

The present study provides evidence that heat shock factor (HSF) may be involved in a transacting factor modulating multidrug resistance 1 (MDR1) gene. In conjunction with the presence of several heat shock elements (HSEs) in the 5' region of the MDR1 gene, we compared the level of HSF which binds to HSEs in multidrug-resistant P388/M and FM3A/M cells with that in their parental counterparts. Under unstressed condition, these multidrug-resistant cells showed constitutive HSF DNA-binding activity in the nucleus of the cells, whereas their parental counterparts did not show detectable HSF DNA-binding activity. We found that H-87, protein kinase A inhibitor, inhibited HSF DNA-binding activity in heat-shocked P388/M cells and also suppressed the levels of hsp90 and hsp70. These results demonstrated that HSF might be an important transcriptional regulator for inducing MDR1 gene, and modulation of HSF activity might be a useful potential target for reversing MDR.

Animals↗
PubMed1994

The thiol-specific antioxidant protein from human brain: gene cloning and analysis of conserved cysteine regions.

The complete cDNA encoding human thiol-specific antioxidant protein (PRP) was isolated from a human brain cDNA library in the lambda Zap expression vector. An open reading frame (ORF) was identified and found to encode a polypeptide of 197 aa with a M(r) of 21,729. The cDNA contained 98 bp of 5'-untranslated sequence (UTR) and 259 bp of 3'-UTR containing a poly(A) signal, AATAAA. Expression of the human PRP cDNA in Escherichia coli yielded a functionally active protein. The observed local sequence homologies between human PRP and other homologous proteins whose functions have not yet been defined give important insight into elucidating the biochemical function of a new protein family which has highly conserved regions containing cysteine.

Amino Acid Sequence↗
PubMed1994

Purification and characterization of thiol-specific antioxidant protein from human red blood cell: a new type of antioxidant protein.

A thiol-specific antioxidant protein (Protector Protein, PRP) was purified from human red blood cells (RBC). The PRP exists as a predominant protein in human RBC, which showed distinct thiol-specific antioxidant activities in the presence of dithiothreitol (DTT) as a reducing equivalent. The human RBC PRP (HRPRP) completely inhibited visible absorption spectral changes of oxyhemoglobin, DNA cleavage, and the peroxidation of RBC membrane by a nonenzymatic Fe3+/O2/thiol mixed-function oxidation system capable of generating hydroxyl radical. These observations suggest that HRPRP could act as a new type of antioxidant protein to maintain the RBC integrity by scavenging reactive oxygen species.

Antioxidants↗
PubMed1994

Genome fingerprinting of Salmonella typhi by pulsed-field gel electrophoresis for subtyping common phage types.

The genomic DNA of 39 strains of Salmonella typhi isolated from local residents and patients who had visited countries in the Asian region was analysed for restriction fragment length polymorphisms (RFLP). Pulsed-field gel electrophoretic (PFGE) analysis of Xba I- and Spe I-generated genomic restriction fragments established 22 PFGE types whereas phage typing differentiated the 39 isolates into 9 distinct phage types. This study showed that PFGE is more discriminatory than phage typing as it is capable of subtyping S. typhi strains of the same phage types. Genetic relatedness among the isolates was determined. Seven major clusters were identified at SABs of > 0.80 and the remaining 13 isolates were distributed into minor clusters which were related at SABs of less than 0.80. In conclusion, PFGE analysis in conjunction with distance matrix analysis served as a useful tool for delineating common S. typhi phage types of diverse origins from different geographical locales and separated in time.

Adolescent↗
PubMed1994

Vibrio cholerae 0139 'Bengal' in Singapore.

Vibrio cholerae 0139 was isolated from five patients with cholera-like illness. All were imported cases. Laboratory investigations found our five isolates in show similar morphological, biochemical and serological characteristics to the V. cholerae 0139 strains causing epidemics in Bangladesh and India. Our isolates were toxin producers resistant to streptomycin and co-trimoxazole. No local transmission was known to have occurred following introduction of these imported cases.

Adult↗
PubMed1993

Removals of hydrogen peroxide and hydroxyl radical by thiol-specific antioxidant protein as a possible role in vivo.

Thiol-specific antioxidant protein (Protector Protein; PRP) from Saccharomyces cerevisiae was found to remove hydrogen peroxide and hydroxyl radical in the presence of dithiothreitol (DTT). Without DTT as a reducing equivalent, the antioxidant protein did not show the activities for destroying hydrogen peroxide and hydroxyl radical. N-ethylmaleimide (NEM) was observed to prevent the PRP from both removing hydrogen peroxide and protecting the cleavage of DNA. These observations suggest that the sulfhydryl of cysteine in PRP could function as a strong nucleophile to attack and destroy H2O2 and .OH.

Antioxidants↗
PubMed1993

Epidemiology of typhoid fever in Singapore.

A total of 1452 cases of typhoid fever was notified in Singapore from 1980-9. The morbidity rates of indigenous cases showed a steady decline from 5.9 per 100,000 population in 1980 to 1.2 per 100,000 population in 1989. The mean case fatality was 0.8%. Children, adolescents and young adults were most susceptible to typhoid fever. There was no significant difference in morbidity rates between the major ethnic groups. The vast majority of indigenous cases were sporadic while outbreaks accounted for almost one third of them. Food was the main vehicle of transmission. The commonest indigenous phage types were B1, D1 and A. Antimicrobial resistance was infrequently seen. The proportion of imported cases rose from 32% in 1980 to 72% in 1989. Almost half (48.5%) of all imported cases were local residents who contracted typhoid fever while travelling in endemic countries. As imported cases assume greater importance in the epidemiology of typhoid fever in Singapore, further drop in typhoid fever incidence would require reduction of travel-related cases through greater awareness of food hygiene and effective vaccination.

Adolescent↗
PubMed1992

A 7-day course of ciprofloxacin for enteric fever.

A prospective, open and non-randomised clinical trial using a 7-day short course of oral ciprofloxacin 500 mg twice daily was conducted on 25 adult patients with bacteraemic enteric fever. Twenty-four patients (96%) were cured and there was one treatment failure. Two patients with typhoid fever relapsed 6 weeks after finishing treatment. Defervescence of fever was rapid (median: 4 days) and the duration of hospitalisation was short (median: 8 days). Both factors resulted in patient satisfaction. A short-course regime of ciprofloxacin for the treatment of enteric fever, is therefore, highly promising.

Administration, Oral↗
PubMed1992

Pasteurella multocida infection in Singapore.

A case of Pasteurella multocida infection in Singapore is presented. The patient was a 21-year-old Chinese male who developed fever and cellulitis with abscess formation of his right index finger after it was bitten by a stray cat. The organism was isolated in pure culture and identified as Pasteurella multocida subspecies septica. The patient responded to antibiotic therapy and had an uneventful recovery.

Adult↗
PubMed1992

Enteropathogenic Escherichia coli as a cause of diarrhoea among children in Singapore.

Enteropathogenic Escherichia coli (EPEC) was isolated from 2.7% of 2983 children under 3 years of age with diarrhoea in Singapore. Of the nine serotypes identified, the most common were 0126:K71(B16), 086:K61(B7) and 0127:K63(B8). Infants were at the greatest risk of contracting gastroenteritis due to EPEC, and female children were slightly more susceptible than males. Antimicrobial susceptibility tests showed that the EPEC strains were generally resistant to ampicillin, streptomycin, tetracycline and triple sulpha, but highly sensitive to ceftriaxone and gentamicin.

Anti-Bacterial Agents↗
PubMed1992

Prevalence of bacterial agents of diarrhoeal disease at the National University Hospital, Singapore and their resistance to antimicrobial agents.

Over a 50-month period, 4,508 stool specimens from patients with diarrhoea were bacteriologically examined at the National University Hospital, Singapore. Salmonella serotypes other than the typhoid and paratyphoid bacilli were the most common finding, being isolated in 10.8% of cases. Campylobacter jejuni was unexpectedly infrequent (1.9%); Aeromonas hydrophila was found in 1.8%. No other aerobic pathogen occurred in more than 1% of cases. Clostridium difficile was sought only when requested, and was isolated from 9.6% of cases tested. Testing for enteropathogenic Escherichia coli was limited to children under 1 year old. Gentamicin was active against the greatest number of aerobic isolates, followed by chloramphenicol and cotrimoxazole. The C. difficile isolates were all sensitive to metronidazole.

Aeromonas hydrophila↗
PubMed1992

Diagnostic value of the Widal test for typhoid fever in Singapore.

A study was conducted to assess the diagnostic value of the Widal test in patients with bacteraemic typhoid fever. The Widal test was carried out on 25 bacteriologically proven cases of typhoid fever and 50 patients with non-typhoid fever. All the patients with non-typhoid fever had an O agglutinin titre of less than 1:40, while 82% had an H agglutinin titre of less than 1:40. In the patients with typhoid fever, 56% had an O agglutinin titre of greater than or equal to 1:40 and 72% had an H agglutinin titre of greater than or equal to 1:40. Typhoid patients with titres greater than or equal to 1:40 for O and H antigens of Salmonella typhi were significantly different (P less than 0.01) from those with non-typhoid fever. The O agglutinin was highly specific (100%) in the diagnosis of the disease. The study shows that a single Widal test is useful in the diagnosis of typhoid fever in Singapore.

Adolescent↗
PubMed1992

A one-year study of enteric Campylobacter infections in Singapore.

A total of 7344 inpatients with diarrhoea were investigated for Campylobacter infections in Singapore over one year. Campylobacter species were recovered from 1.2% of diarrhoeal stools; 70.3% of the 91 campylobacters were from children under 5 years of age. Further identification of these isolates showed that 89% were Campylobacter jejuni and 10.9% were C. coli, and a high level of resistance to erythromycin was observed among them. Concomitant isolation of Salmonella species or Shigella species was achieved in eight of the Campylobacter-infected patients. Campylobacter enteritis occurred throughout the year, with the highest isolation rate being recorded in September.

Campylobacter↗