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Biomedical subjects

W Lim

Publications and source records attributed to W Lim.

At least 37 records · Page 2Linked to original sources
PubMed2001

Characterization of a human H9N2 influenza virus isolated in Hong Kong.

Two H9N2 viruses were isolated, for the first time, from humans in Hong Kong in 1999. Isolation of influenza viruses with a novel subtype of the hemagglutinin (HA) drew attention of health care authorities worldwide from the view of pandemic preparedness. Sequence analysis of the HA genes reveals that HA of A/Hong Kong/1073/99 (H9N2) is most closely related to that of A/quail/HK/G1/97 (H9N2) that contains the internal genes similar to those of Hong Kong/97 (H5N1) viruses. Phylogenetic and antigenic analyses demonstrated the diversity among H9 HA. A/Hong Kong/1073/99 was shown to cause a respiratory infection in Syrian hamsters, suggesting that the virus can replicate efficiently in mammalian hosts. We developed a whole virion test vaccine with a formalin-inactivated egg-grown HK1073. Intraperitoneal administration of the vaccine twice to hamsters conferred a complete protection against challenge infection by the MDCK cell-grown homologous virus. Receptor specificity of HK1073 appeared different from that of other avian influenza viruses of H9 subtype which recognize preferentially alpha-2,3 linked sialic acid. Hemagglutination of HK1073 with guinea pig erythrocytes was inhibited by both alpha-2,3 and alpha-2,6 linked sialic acid containing polymers. These data suggested that HK1073 had acquired a broader host range, including humans. Together with data so far available, the present study suggested that isolation of the H9 influenza viruses from humans requires precaution against the emergence of a novel human influenza.

Animals↗
PubMed2001

Effect of asymmetry on the loss of chaos synchronization.

We investigate the effect of asymmetry of coupling on the bifurcation mechanism for the loss of synchronous chaos in coupled systems. It is found that only when the symmetry-breaking pitchfork bifurcations take part in the process of the synchronization loss for the case of symmetric coupling, the asymmetry changes the bifurcation scenarios of the desynchronization. For the case of weak coupling, pitchfork bifurcations of asynchronous periodic saddles are replaced by saddle-node bifurcations, while for the case of strong coupling, pitchfork bifurcations of synchronous periodic saddles transform to transcritical bifurcations. The effects of the saddle-node and transcritical bifurcations for the weak asymmetry are similar to those of the pitchfork bifurcations for the symmetric-coupling case. However, with increasing the "degree" of the asymmetry, their effects change qualitatively, and eventually become similar to those for the extreme case of unidirectional asymmetric coupling.

Journal Article↗
PubMed2001

Bicritical scaling behavior in unidirectionally coupled oscillators.

We study the scaling behavior of period doublings in a system of two unidirectionally coupled parametrically forced pendulums near a bicritical point where two critical lines of period-doubling transition to chaos in both subsystems meet. When crossing a bicritical point, a hyperchaotic attractor with two positive Lyapunov exponents appears, i.e., a transition to hyperchaos occurs. Varying the control parameters of the two subsystems, the unidirectionally coupled parametrically forced pendulums exhibit multiple period-doubling transitions to hyperchaos. For each transition to hyperchaos, using both a "residue-matching" renormalization group method and a direct numerical method, we make an analysis of the bicritical scaling behavior. It is thus found that the second response subsystem exhibits a new type of non-Feigenbaum scaling behavior, while the first drive subsystem is in the usual Feigenbaum critical state. The universality of the bicriticality is also examined for several different types of unidirectional couplings.

Journal Article↗
PubMed2001

The p38 mitogen-activated kinase pathway regulates the human interleukin-10 promoter via the activation of Sp1 transcription factor in lipopolysaccharide-stimulated human macrophages.

Interleukin-10 (IL-10), a pleiotropic cytokine that inhibits inflammatory and cell-mediated immune responses, is produced by a wide variety of cell types including T and B cells and monocytes/macrophages. Regulation of pro- and anti-inflammatory cytokines has been suggested to involve distinct signaling pathways. In this study, we investigated the regulation of the human IL-10 (hIL-10) promoter in the human monocytic cell line THP-1 following activation with lipopolysaccharide (LPS). Analysis of hIL-10 promoter sequences revealed that DNA sequences located between base pairs -652 and -571 are necessary for IL-10 transcription. A computer analysis of the promoter sequence between base pairs -652 and -571 revealed the existence of consensus sequences for Sp1, PEA1, YY1, and Epstein-Barr virus-specific nuclear antigen-2 (EBNA-2)-like transcription factors. THP-1 cells transfected with a plasmid containing mutant Sp1 abrogated the promoter activity, whereas plasmids containing the sequences for PEA1, YY1, and EBNA-2-like transcription factors did not influence hIL-10 promoter activity. To understand the events upstream of Sp1 activation, we investigated the role of p38 and extracellular signal-regulated kinase mitogen-activated protein kinases by using their specific inhibitors. SB202190 and SB203580, the p38-specific inhibitors, inhibited LPS-induced IL-10 production. In contrast, PD98059, a specific inhibitor of extracellular signal-regulated kinase kinases, failed to modulate IL-10 production. Furthermore, SB203580 inhibited LPS-induced activation of Sp1, as well as the promoter activity in cells transfected with a plasmid containing the Sp1 consensus sequence. These results suggest that p38 mitogen-activated protein kinase regulates LPS-induced activation of Sp1, which in turn regulates transcription of the hIL-10 gene.

Arabidopsis Proteins↗
PubMed2001

Mechanism for the riddling transition in coupled chaotic systems.

We investigate the loss of chaos synchronization in coupled chaotic systems without symmetry from the point of view of bifurcations of unstable periodic orbits embedded in the synchronous chaotic attractor (SCA). A mechanism for direct transition to global riddling through a transcritical contact bifurcation between a periodic saddle embedded in the SCA and a repeller on the boundary of its basin of attraction is thus found. Note that this bifurcation mechanism is different from that in coupled chaotic systems with symmetry. After such a riddling transition, the basin becomes globally riddled with a dense set of repelling tongues leading to divergent orbits. This riddled basin is also characterized by divergence and uncertainty exponents, and thus typical power-law scaling is found.

Journal Article↗
PubMed2001

Some problematic behaviors in Alzheimer's dementia.

We examined 18 patients with problematic behaviors in relation to their individual characteristics and their possible relationship to certain aspects of dementia namely cognitive impairment, stage of illness, language impediment and functional disability. They formed part of an earlier assessment of 94 patients with dementia-related problems. Ten had altered eating habits and eight (8.5%) of them had hyperphagia. One exhibited an incomplete form of Kluver-Bucy Syndrome. Two had pathological stealing and one scatolia (smearing of faeces). The remaining had bizzare behaviors such as screaming and head banging. The majority of the patients were in the moderate category in relation to the four domains tested. The study revealed that behavioral problems in the more severe dementia becomes less of a problem to the caregivers and others. These behaviors could dramatically affect the social and interpersonal relationships resulting in community, family and caregiver burden.

Journal Article↗
PubMed2001

Infection of a child in Hong Kong by an influenza A H3N2 virus closely related to viruses circulating in European pigs.

Influenza virus A/Hong Kong/1774/99, isolated from a young child with mild influenza, was shown to be similar in its antigenic and genetic characteristics to H3N2 viruses circulating in pigs in Europe during the 1990s and in particular to be closely related to viruses isolated from two children in the Netherlands in 1993. Similar viruses had previously not been identified outside Europe. Although there is little evidence as to how the child contracted the infection, it appears likely that pigs in southern China were the source of infection. Characteristics shared with the European swine viruses include resistance to the anti-influenza drugs amantadine and rimantadine. Thus not only does this incident once again highlight the potential of pigs as a source of novel human influenza viruses, but also indicates the potential for emergence of amantadine-resistant human viruses.

Amantadine↗
PubMed2001

Universal antenatal human immunodeficiency virus testing in Hong Kong: consensus statement.

Following the recommendations of the Advisory Council on AIDS, Hong Kong, the Hospital Authority announced plans to introduce universal antenatal screening for human immunodeficiency virus infection and hence, a consensus conference was held to discuss strategies for implementing such screening in Hong Kong. This paper reports the discussions of the consensus conference. The consensus meeting group consisted of 15 clinicians and scientists from Hong Kong, Macau, and Thailand. Seven commonly asked questions concerning mother-to-child transmission of human immunodeficiency virus were selected for discussion by the participating panellists. Information on the laboratory diagnosis of human immunodeficiency virus infection and the efficacy of preventive measures in reducing mother-to-child transmission of human immunodeficiency virus were reviewed. Data from local studies was also presented and discussed. The timing, potential problems, and cost issues involved in testing all pregnant women in Hong Kong for human immunodeficiency virus were then considered.

Adult↗
PubMed2000

Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship between H9N2 and H5N1 human isolates.

In 1997, 18 cases of influenza in Hong Kong (bird flu) caused by a novel H5N1 (chicken) virus resulted in the deaths of six individuals and once again raised the specter of a potentially devastating influenza pandemic. Slaughter of the poultry in the live bird markets removed the source of infection and no further human cases of H5N1 infection have occurred. In March 1999, however, a new pandemic threat appeared when influenza A H9N2 viruses infected two children in Hong Kong. These two virus isolates are similar to an H9N2 virus isolated from a quail in Hong Kong in late 1997. Although differing in their surface hemagglutinin and neuraminidase components, a notable feature of these H9N2 viruses is that the six genes encoding the internal components of the virus are similar to those of the 1997 H5N1 human and avian isolates. This common feature emphasizes the apparent propensity of avian viruses with this genetic complement to infect humans and highlights the potential for the emergence of a novel human pathogen.

Animals↗
PubMed2000

Evidence for participation of RNA 1-encoded elicitor in Cowpea mosaic virus-mediated concurrent protection.

The cowpea (Vigna unguiculata) line Arlington, inoculated with Cowpea mosaic virus (CPMV), showed no symptoms, and no infectivity or accumulation of capsid antigen was detected at several days after inoculation. Coinoculation, but not sequential inoculation, of CPMV with similar concentrations of another Comovirus; Cowpea severe mosaic virus (CPSMV), resulted in reduced numbers of CPSMV-induced lesions. This apparent, CPMV-mediated reduction in number of CPSMV-induced infection centers was termed concurrent protection. We report results obtained by inoculating two nearly isogenic cowpea lines derived from a CPMV-susceptible cowpea crossed to Arlington, one line CPMV-susceptible and the other resistant. The CPMV virions B and M, encapsidating genomic RNAs 1 and 2, respectively, were extensively purified by gradient centrifugation. In the CPMV-resistant cowpea, either CPMV or CPMV B affected concurrent protection against CPSMV and against two distinct non-Comoviruses: Cherry leafroll virus and Southern bean mosaic virus. Adding CPMV M to the inoculum did not enhance CPMV-B-mediated protection. CPMV B was ineffective in protecting CPMV-susceptible cowpea. We postulate that CPMV-mediated concurrent protection is elicited in CPMV-resistant cowpea by a CPMV RNA-1-encoded factor and acts to reduce accumulation or spread of CPMV and certain coinoculated challenging viruses in or from the inoculated cell. Coinoculated CPMV did not protect CPMV-resistant cowpea against Tomato bushy stunt virus or Cucumber mosaic virus.

Comovirus↗
PubMed2000

Inhibition of apamin-sensitive K+ current by hypoxia in adult rat adrenal chromaffin cells.

The effect of hypoxia on small-conductance Ca(2+)-activated K+ current was investigated in a study of adult rat adrenomedullary chromaffin cells (AMCs), which were maintained in short-term culture. The nystatin-perforated, whole-cell patchclamp technique was used to study the effect of hypoxia with minimum perturbation of the intracellular milieu. Under voltage-clamp conditions, acute hypoxia (P(O2) approximately equal to 25 mmHg) suppressed the whole-cell outward currents of more than half the AMCs (24/46). This suppression was eliminated after application of apamin (400 nM), a selective inhibitor of small-conductance Ca(2+)-activated K+ current (I(SK)(Ca)) (n=5), suggesting that an apamin-sensitive component of whole-cell currents is suppressed during hypoxia. In contrast to I(SK)(Ca), Ca2+ current (I(Ca)) (n=10) was not affected by hypoxia. Finally, under current-clamp conditions, hypoxia reversibly depolarized the resting membrane potential of adult AMCs (34/40). Apamin, however, eliminated the hypoxia-induced depolarization (400 nM) (7/8), suggesting that hypoxic depolarization is related to the suppression of I(SK(Ca). From the above results, we conclude that adult AMCs are sensitive to hypoxia, and that I(SK)(Ca) contributes to the hypoxia-induced suppression of whole-cell outward current and depolarization of the resting membrane potential in adult AMCs.

Adrenal Medulla↗
PubMed2000

Voltage-dependent K(+) currents in spiral prominence epithelial cells of rat cochlea.

It has been suggested that spiral prominence is associated with ion transport, but the characterization of ion channels has not been explored so far. We studied the electrical properties and ion conductances of the spiral prominence epithelial cells (SPECs), which are epithelial cells covering the luminal side of spiral prominence, in the upper turn of neonatal rat cochlea using a whole-cell variant patch clamp technique. The cell capacitance was 16.3+/-2.1 pF (n=33) and the resting membrane potential was -68. 9+/-2.5 mV (n=14) in perilymph-like bath solution. It was found that those SPECs possess a large voltage-activated, outwardly rectifying K(+) current and a small inwardly rectifying K(+) current. The outward K(+) current was activated by depolarizing pulses more positive than -30 mV, and sensitive to tetraethylammonium chloride (20 mM), 4-aminopyridine (10 mM), but not to Ba(2+) (0.5 mM). Tail current analysis revealed that it was primarily K(+)-selective. The time course of activation was well fitted by an exponential function raised to second power. The small inwardly rectifying K(+) current was sensitive to Ba(2+) (0.5 mM), and the Ba(2+)-sensitive current was K(+)-selective. In cell-attached or inside-out patch recordings, no discernible K(+) channel currents were found in the apical membrane of SPECs. Based on these results, we conclude that SPECs have two types of voltage-dependent K(+) currents, which are most likely located in the basolateral membrane.

Animals↗
PubMed2000

Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong.

The first outbreak of avian influenza A (H5N1) occurred among humans in Hong Kong in 1997. To estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of H5N1 antibody among health care workers (HCWs) exposed to H5N1 case-patients with the prevalence among nonexposed HCWs. Information on H5N1 case-patient and poultry exposures and blood samples for H5N1-specific antibody testing were collected. Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). The difference remained significant after controlling for poultry exposure (P=.01). This study presents the first epidemiologic evidence that H5N1 viruses were transmitted from patients to HCWs. Human-to-human transmission of avian influenza may increase the chances for the emergence of a novel influenza virus with pandemic potential.

Adult↗
PubMed2000

HIV-1 infected women and prenatal care utilization: barriers and facilitators.

In an effort to understand issues affecting prenatal care access and utilization from the perspectives of human immunodeficiency virus (HIV)-infected women who receive inadequate prenatal care, we conducted three in-depth qualitative and quantitative interviews. From a thematic analysis of the narrative interviews, four broad areas emerged as pertinent to these women's prenatal care experiences. These were issues related to pregnancy, HIV, psychosocial conditions, and the health care system. For these women, the barriers to prenatal care utilization included the unexpected and unplanned nature of the pregnancy and mental health issues related to HIV infection. Poverty, periodic homelessness, addiction to illicit substances, and lack of social support were also important barriers. Furthermore, perceptions of the health care system as threatening, including fears related to consequences of disclosing illicit activities, discrimination, and breach of confidentiality emerged as salient barriers. Facilitating factors included the pregnancy being experienced as a life-transforming event, concern for their children, especially preventing HIV-1 vertical transmission, availability of treatment, and support from health care professionals. Prominent throughout the interviews were the women's mental health concerns and need for professional support.

Adult↗
PubMed2000

Evolutionary characterization of the six internal genes of H5N1 human influenza A virus.

The entire nucleotide sequences of all six internal genes of six human H5N1 influenza A viruses isolated in Hong Kong in 1997 were analysed in detail from a phylogenetic point of view and compared with the evolutionary patterns of the haemagglutinin and neuraminidase genes. Despite being isolated within a single year in the same geographical location, human H5N1 viruses were characterized by a variety of amino acid substitutions in the ribonucleoprotein complex [PB2, PB1, PA and nucleoprotein (NP)] as well as the matrix (M) proteins 1 and 2 and nonstructural (NS) proteins 1 and 2. The presence of previously reported amino acid sequences specific for human strains was confirmed in the PB2, PA, NP and M2 proteins. Nucleotide and amino acid sequence identities of the six internal genes of H5N1 viruses examined here were separated into at least two variant groups. In agreement with the above result, phylogenetic trees of the six internal genes of human H5N1 viruses were generally composed of two minor clades. Additionally, variable dendrogram topologies suggested that reassortment among viruses contributed further to the genetic variability of these viruses. As a result, it became clear that human H5N1 viruses are characterized by divergent gene constellations, suggesting the possible occurrence of genetic reassortment between viruses of the two evolutionary lineages.

DNA-Directed RNA Polymerases↗
PubMed1999

Characterization of the surface proteins of influenza A (H5N1) viruses isolated from humans in 1997-1998.

Influenza A (H5N1) viruses infected humans in Hong Kong between May and December, 1997. Sixteen viruses, including 6 from fatal cases, were isolated during this outbreak. Molecular analysis of the surface proteins genes encoding the hemagglutinin (HA) and neuraminidase (NA) of these H5N1 isolates, of a subtype not previously known to infect humans, are presented. The 16 human H5 HA sequences contain multiple basic amino acids adjacent to the cleavage site, a motif associated with highly pathogenic avian influenza A viruses. The phylogenetic relationship among both avian and human H5 hemagglutinins indicates that the human isolates are related directly to isolates that circulated among chickens in the live poultry markets in Hong Kong prior to and during the outbreak in humans. HA sequences from the human isolates and a recent chicken isolate represent a separate clade, within which there are two subgroups that are distinguishable antigenically and by the presence of a potential glycosylation site. Likewise the N1 neuraminidases of the human H5 isolates represent a clade that is evolutionarily distinct from previously characterized N1 neuraminidases. The recent human H5N1 virus NA genes are avian-like, indicating direct introduction from an avian source rather than evolution of a human N1 NA. All of the 16 human NA genes encode a shortened stalk due to a 19-amino acid deletion, also found in the recent avian H5N1 isolates from Hong Kong. Two unique amino acids were identified in the N1 NAs of the recent human isolates; however, it is not known if these residues influence host range. Neither the HA nor the NA genes of the human H5N1 virus isolates show evidence of adaptive changes during the outbreak. Although analyses of the surface protein genes of the H5N1 viruses from this outbreak did not provide immediate answers regarding the molecular basis for virulence, the analyses provided clues to potentially important areas of the genes worth further investigation.

Adolescent↗
PubMed1999

Trends in human immunodeficiency virus (HIV) counseling, testing, and antiretroviral treatment of HIV-infected women and perinatal transmission in North Carolina.

Since 1993, trends in perinatal human immunodeficiency virus (HIV) transmission have been monitored by use of chart review of patients identified at a central diagnostic laboratory. In the population studied, either pre- or postnatal antiretroviral therapy to the infant increased from 21% in 1993 to 95% in 1997. Concurrently, the number of HIV-infected infants declined from 25 in 1993 to 4 in 1997. The complete Pediatric AIDS Clinical Trials Group Protocol 076 regimen was the most effective in reducing transmission (3.1%). Twenty-two of 35 infants who became infected in 1995-1997 had mothers who did not receive antiretroviral therapy, although counseling practices improved with time. In 1995, 87% of the mothers of HIV-seropositive infants were counseled, whereas in 1997, 96% were counseled (P<.005). None of 59 infants tested had high-level phenotypic zidovudine resistance, although 5 (8.8%) of 57 infants had virus isolates with at least one mutation in the reverse transcriptase gene associated with reduced phenotypic susceptibility to zidovudine.

Anti-HIV Agents↗