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Biomedical subjects

W Lim

Publications and source records attributed to W Lim.

At least 19 recordsLinked to original sources
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

Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays.

From May to December 1997, 18 cases of mild to severe respiratory illness caused by avian influenza A (H5N1) viruses were identified in Hong Kong. The emergence of an avian virus in the human population prompted an epidemiological investigation to determine the extent of human-to-human transmission of the virus and risk factors associated with infection. The hemagglutination inhibition (HI) assay, the standard method for serologic detection of influenza virus infection in humans, has been shown to be less sensitive for the detection of antibodies induced by avian influenza viruses. Therefore, we developed a more sensitive microneutralization assay to detect antibodies to avian influenza in humans. Direct comparison of an HI assay and the microneutralization assay demonstrated that the latter was substantially more sensitive in detecting human antibodies to H5N1 virus in infected individuals. An H5-specific indirect enzyme-linked immunosorbent assay (ELISA) was also established to test children's sera. The sensitivity and specificity of the microneutralization assay were compared with those of an H5-specific indirect ELISA. When combined with a confirmatory H5-specific Western blot test, the specificities of both assays were improved. Maximum sensitivity (80%) and specificity (96%) for the detection of anti-H5 antibody in adults aged 18 to 59 years were achieved by using the microneutralization assay combined with Western blotting. Maximum sensitivity (100%) and specificity (100%) in detecting anti-H5 antibody in sera obtained from children less than 15 years of age were achieved by using ELISA combined with Western blotting. This new test algorithm is being used for the seroepidemiologic investigations of the avian H5N1 influenza outbreak.

Adolescent↗
PubMed1998

Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.

An avian H5N1 influenza A virus (A/Hong Kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza. Serologic analysis indicated the presence of an H5 hemagglutinin. All eight RNA segments were derived from an avian influenza A virus. The hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. The virus caused 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. These results may have implications for global influenza surveillance and planning for pandemic influenza.

Amino Acid Sequence↗
PubMed1998

High prevalence of hepatitis C virus genotype 6 among certain risk groups in Hong Kong.

The genotype of hepatitis C virus (HCV) of 172 HCV-RNA positive serum specimens taken from patients with chronic liver diseases, thalassaemia major, chronic renal failure (CRF), haemophilia and intravenous drug abusers (IVDA) was determined by analysis of the amplified 5'UTR region by genotype-specific oligonucleotide probes and restriction fragment length polymorphism (RFLP). Six different genotypes and subtypes (1a, lb, 2, 3, 4 and 6) were found. Genotype lb was the predominant genotype among patients with chronic liver diseases (69.6%), followed by genotype 6 (18.8%), which was similar to that reported for blood donors in earlier studies. Pronounced differences in the distribution of genotypes were seen between the four risk groups. Patients with CRF had a similar distribution to those with chronic liver diseases, whilst the greatest diversity of genotypes was seen in patients with haemophilia, which was expected since they were given factor VIII manufactured overseas. Genotype 6 was particularly prominent in patients with thalassaemia major (50%) and IVDA (62.5%). It is possible that clonal spread of HCV genotype 6 has taken place among a closed subset of the population in Hong Kong through intravenous drug abuse.

Female↗
PubMed1998

Labour ward midwifery staff epidural knowledge and practice.

A survey was conducted amongst labour ward midwives at our hospital to evaluate education, knowledge and attitudes toward the management of epidural analgesia in labour. Sixty of 80 distributed forms were returned, giving a 75% response rate. Forty-two per cent of respondents had more than ten years' practice experience. Only 51% achieved a predetermined pass score for knowledge about epidural analgesia. Though most had received formal education about epidural analgesia, 35% felt postgraduate education was insufficient. A majority of midwives supported epidural analgesia on demand (78%), during established labour (74%), or for women at increased risk of caesarean section (82%). Midwives with lower knowledge levels were more likely to recommend epidural analgesia early in labour to multiparous women (P = 0.001) and to women with either a small or a large baby (P = 0.06). The majority of midwives (93%, 70% and 65%) would "almost always" top-up women with cardiac or medical diseases, multiple pregnancy or hypertensive disease, respectively. A clear requirement for ongoing education, with input from the anaesthetic department, was identified, irrespective of personal experience. Practice patterns are discussed and recommendations made with respect to improvement of epidural analgesia management and continuing education.

Adult↗
PubMed1998

Obstetricians' knowledge and attitudes toward epidural analgesia in labour.

A survey of all registered obstetrician/gynaecologists in Western Australia (n = 79) was conducted to obtain information regarding their level of knowledge about epidural analgesia (EA) in labour and its complications, their sources of information about EA, and their opinions regarding its role in labour and effect on progress of labour. Response rate was 68%. Most respondents had only received lectures about EA after specialist training and 20% did not achieve an adequate knowledge score. Those of less than five years' experience achieved significantly better scores. Over a third did not favour EA in labour until active labour was established, though 90% would recommend it by late first stage in those with a potentially complicated delivery. For women with cardiac or significant medical disease aggravated by labour, 18% would wait until the late first or second stage before suggesting EA. Seventy-seven per cent believed EA prolonged the second stage of labour, though opinion varied regarding EA effects on the duration and progress of first and third stages. Up to thirty minutes delay before epidural placement is acceptable to 87%. This survey suggests that there is both a demand and a need for greater education about EA in labour, particularly with respect to EA side-effects, complications and effects on labour, in the subgroup of obstetricians who have been in obstetric practice more than five years.

Adult↗
PubMed1997

Sera from amyotrophic lateral sclerosis patients reduce high-voltage activated Ca2+ currents in mice dorsal root ganglion neurons.

This study investigated the effects of sera from amyotrophic lateral sclerosis (ALS) patients on high voltage activated (HVA) Ca2+ current in mice dorsal root ganglion (DRG) cells using whole-cell voltage-clamp method. Mice were injected with sera from healthy adults, from patients with other neurological diseases, and from patients with the sporadic form of ALS, for a period of 3 days. Sera from five of six ALS patients reduced HVA Ca2+ current amplitude. The peak Ca2+ current was significantly reduced by ALS sera while the sera from healthy adults and patients with other diseases did not alter Ca2+ current. The inactivation kinetics was altered by ALS sera, and the half-inactivation voltage shifted to more negative potential in ALS group. These results suggest that sporadic ALS serum factors may exert interactions with the HVA Ca2+ channel in DRG cells to reduce the Ca2+ current.

Adult↗
PubMed1997

Ca2+-channel-dependent and -independent inhibition of exocytosis by extracellular ATP in voltage-clamped rat adrenal chromaffin cells.

Membrane currents and capacitance were measured to examine the effects of extracellular ATP on exocytosis in voltage-clamped rat adrenal chromaffin cells. ATP reversibly inhibited Ca2+ current (ICa) and exocytosis. The dependency of exocytosis on ICa evoked by 1-s depolarizations was determined. However, inhibition of exocytosis was 2.6 times larger than that estimated from the reduction of ICa, implying the existence of a Ca2+-channel-independent pathway. This inhibition did not rely on a further reduction of the intracellular Ca2+ concentration spike. ATP reduced the rate of exocytosis induced by clamping the intracellular Ca2+ concentration. Pertussis toxin blocked the inhibitory effects of ATP on ICa and exocytosis. Although RB-2, a P2Y antagonist, blocked the inhibitory effect of ATP on ICa, RB-2 itself produced large increase or decrease in membrane capacitance. Adenosine inhibited ICa via a pertussis-toxin-sensitive pathway but did not significantly inhibit exocytosis. Our data show that extracellular ATP inhibits exocytosis via inhibition of ICa by activation of a pertussis-toxin-sensitive G-protein linked to P2Y receptors. Furthermore, our data strongly suggest that ATP activates another pathway, which is also G-protein dependent and accounts for the majority of the inhibitory effect of ATP on exocytosis.

Adenosine Triphosphate↗
PubMed1997

Postoperative epidural infusion: a randomized, double-blind, dose-finding trial of clonidine in combination with bupivacaine and fentanyl.

The aim of this randomized, double-blind trial of postoperative thoracic epidural analgesic infusions was to determine whether clonidine at 10 microg/h (group C10, n = 22), 15 microg/h (Group C15, n = 24), or 20 microg/h (Group C20, n = 24) improved postoperative analgesia in patients undergoing abdominal gynecologic surgery, without side effects or hemodynamic changes, when added to a 5-mL/h infusion of 0.125% bupivacaine and fentanyl 2 microg/mL (Group CO, n = 22). The 24-h study infusion was supplemented, as required, by patient-controlled epidural fentanyl. Groups were similar for age, weight, duration, and type of surgery. Clonidine produced a dose-dependent improvement in analgesia at rest. Only 20 microg/h significantly increased the percentage of patients who experienced no pain with coughing (relative risk 1.44, 95% confidence interval 1.24-1.94), reduced pain scores with coughing (P < 0.05), and significantly lowered supplementary fentanyl requirements (P < 0.05). Groups were similar for sedation, pruritus, nausea, time to ambulation, and satisfaction with analgesia. Clonidine produced a dose-dependent decrease in blood pressure and pulse rate and an increase in vasopressor requirement (P < 0.01). Epidural clonidine infused at 20 microg/h improves analgesia during coughing when combined with epidural bupivacaine-fentanyl in patients undergoing lower abdominal surgery but is associated with hemodynamic changes and increased vasopressor requirement.

Adrenergic alpha-Agonists↗
PubMed1997

Hippocampal volumetry with magnetic resonance imaging: a cost-effective validated solution.

PURPOSE: The clinical utility of hippocampal volumetry is well documented, but the materials and techniques required to perform the procedure are not widely available outside major research centers. We describe a personal computer-based method of volumetric data analysis. METHODS: Using a 1.0-T scanner, we obtained 2-mm-thick tilted coronal MPRAGE magnetic resonance imaging (MRI) scans of 20 healthy volunteers aged 20-38 years. We used an inexpensive utility program to extract image information and an NIH Image for image analysis. The hippocampal formations were traced with a graphics tablet and landmarks described by Watson et al. (Neurology 1992;42:1743-50). Overlays of individual observers' tracings were used to fine tune the selection of landmarks and boundaries. Filled-in silhouette pairs generated from these "training tracings" were compared to determine how well observers could visually quantify area differences. RESULTS: Visual detection of asymmetry of silhouette pairs was sensitive, but the magnitude of asymmetry was underestimated. We achieved intraobserver coefficients of variation of right/left volume ratios between 0.82 and 3.16 and an interobserver range of volume ratios of 6%. In 20 healthy controls aged 20-38 years, the mean right and left hippocampal volumes were 2,911 mm3 and 2,836 mm3, respectively. The lower limits of normal were 2,217 mm3 for the right and 2,178 mm3 for the left. The mean right/left hippocampal ratio was 1.03, and the limits of normal (3 SD) for this were 0.95 to 1.10. CONCLUSIONS: Hippocampal volumetry can be performed reliably and economically. Our methodology makes it possible for different observers to generate consistent and comparable measurements.

Adult↗
PubMed1996

Perinatal HIV infection and the effect of zidovudine therapy on transmission in rural and urban counties.

OBJECTIVES: To assess health care providers' identification of human immunodeficiency virus (HIV)-exposed infants, to ascertain the prevalence of transplacental or oral zidovudine treatment among infants exposed to HIV, and to estimate the impact of zidovudine use on perinatal transmission in rural and urban North Carolina. DESIGN: Survey of North Carolina newborns tested for HIV infection in 1993 and 1994 compared with the number of anonymous HIV-positive childbearing women. SETTING: North Carolina hospitals, public health clinics, and private physicians' offices. MAIN OUTCOME MEASURES: Rates of identification of HIV-exposed infants and of perinatal HIV-1 transmission, determined by HIV culture and polymerase chain reaction testing in the infants. RESULTS: The proportion of HIV-exposed children in North Carolina who were identified and tested increased from 60% in 1993 to 82% for all of 1994, and to more than 90% for the last quarter of 1994. The HIV-exposed infants born in rural counties were more likely to be recognized than those born in urban counties (P<.001). In 1994, most infants were evaluated relatively early in life: 39% by 1 week of age, 63% by 6 weeks, and 76% by 3 months. Among infants with recognized HIV exposure, transmission decreased significantly between 1993 and 1994, from 21% to 8.5%, respectively (P=.009). After the announcement of the results of the AIDS Clinical Trials Group Protocol 076, zidovudine was given to 75% of HIV-positive women who delivered infants in North Carolina. Only 5.7% of infants who received any zidovudine became infected, compared with 18.9% of infants who received no zidovudine (P=.007). CONCLUSIONS: Health care providers in North Carolina are identifying most of the state's HIV-seropositive pregnant women, treating them with zidovudine, and testing their infants soon after birth for HIV infection. The use of zidovudine in pregnant women and their infants has reduced perinatal HIV transmission in the state.

AIDS Serodiagnosis↗
PubMed1996

Depressor pathway involved in somatosympathetic reflex in cats.

The present study aimed to identify direct vasodepressor pathways from the rostral ventrolateral medulla (RVLM) to the spinal cord and their role in mediation of somatosympathetic reflexes. Vasopressor and depressor areas were identified by stimulating various sites of RVLM electrically and/or chemically in anesthetized cats. Electrical lesions on the pressor areas abolished the pressor response evoked by peripheral C-fiber activation while the depressor response remained. Electrical lesions on the depressor areas decreased the depressor response evoked by A delta-fiber stimulation. To characterize the neurons involved, 17 medullospinal sympathetic neurons were identified electrophysiologically. While most of them were sympathoexcitatory, three medullospinal tract cells were found to be sympathoinhibitory neurons. From these results we concluded that a minor group of neurons in the RVLM is sympathoinhibitory and is involved in mediation of somatosympathetic depressor response.

Animals↗
PubMed1996

The primary antibody repertoire of normal, immunodeficient and autoimmune mice is characterized by differences in V gene expression.

During the last decade, the structure and organization of the immunoglobulin heavy and light chain locis have been defined in mice and humans. Studies on VH gene expression at different stages of development, in different organs and disease states have provided useful insight into the construction of a primary antibody repertoire in mice. Clearly, 3'VH genes 7183, Q52 and Vh11, which are conserved during evolution, are preferentially expressed during early development of the B-lymphocyte repertoire. A preferential use for the V kappa 4 gene family is evident during early B-cell development. The initial development of the primary antibody repertoire is therefore influenced by a restricted set of VH and V kappa gene elements. The restricted B-cell repertoire is subsequently normalized in the periphery, as revealed by stochastic VH gene expression, as a result of exposure to environmental antigens. Obviously, the peripheral B-cell pool characterized by stochastic VH gene expression is selectively replenished by newly generated B cells in bone marrow that preferentially expresses 3'VH genes. The V kappa genes are, however, expressed in a non-random manner in the neonatal and adult B-lymphocyte repertoire that is probably related to VH and V kappa association dynamics and/or positive or negative selection. Interestingly, these characteristics of neonatal and adult primary repertoire are noted in both B1 and B2 lymphocytes. No remarkable age-related differences are evident for VH and V kappa gene expression. In healthy mice, both the mitogen responsive (available) and unstimulated (expressed) B-cell repertoire show similar VH gene expression. Interestingly, VH gene expression varies in different organs which may reflect, or occur as a result of, the specialized function of each organ. For example, J558 gene expression is higher in the peripheral LN where B cells continuously encounter exogenous antigens. The skewed VH and V kappa gene expression noted in immunodeficient and autoimmune lupus-prone mice reflects the impairment of the primary antibody repertoire associated with immunodeficiency and autoimmune disorders.

Animals↗
PubMed1996

Induction stand.

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Anesthesia, Intravenous↗
PubMed1995

Contribution of L- and N-type calcium currents to exocytosis in rat adrenal medullary chromaffin cells.

The excitation-secretion coupling process requires Ca2+ influx through voltage-dependent Ca2+ channels (VDCC) but the contribution of L-type or N-type VDCC during the secretion from adrenal chromaffin cell is still on debate. In this study we explored the contribution of each VDCC to exocytosis in single rat adrenal chromaffin cells. Chromaffin cells were voltage-clamped clamped in the whole-cell recording mode. Ca2+ inward current (ICa) was elicited by depolarization from -70 mV to +10 mV and the change in cell membrane capacitance (Cm) was monitored as an indicator of the resultant exocytosis. The increase in Cm had positive correlation with the amount of ICa and replacing the internal Ca2+ buffer to high EGTA (5 mM) decreased the sensitivity of Cm increase to Ca2+ influx. After blockage of ICa with 100 microM Cd2+, there was no increase in Cm following membrane potential depolarization while INa was intact. To clarify the contribution of each type of VDCC to induce exocytosis during membrane potential depolarization, L- and N-type ICa were blocked selectively by Ca2+ channel antagonists. After blockage of L-type ICa with nicardipine (1 microM), ICa was blocked to 35 +/- 6.2% (mean +/- standard error) of control and the resultant change in Cm was reduced to 38 +/- 4.6% of control. Bay K-8644 (1 microM) enhanced ICa and the similar proportion of Cm was increased by this L-type VDCC agonist. On the other hand omega-conotoxin GVIA (1 microM), an N-type VDCC antagonist, blocked ICa to 60 +/- 4.3% of control and reduced the change in Cm to 58 +/- 3.9% of control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1995

Mechanism of liposome destabilization by polycationic amino acids.

Polycationic amino acids induce the leakage and fusion of liposomes containing anionic lipids. We have investigated the nature and extent of the changes in membrane physical properties caused by these polypeptides which could result in the observed membrane destabilization. We found that in the range of pH 5 to pH 7 both poly-L-histidine and poly-L-lysine were ineffective in shifting the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine, either in the presence of absence of 1-palmitoyl-2-oleoylphosphatidylserine. We also studied the gel to liquid crystalline phase transition properties of 1:1 mixtures of phosphatidylserine and phosphatidylethanolamine, both in dimyristoyl forms as well as the 1-palmitoyl-2-oleoyl forms, as a function of pH and in the presence and absence of polycationic amino acids. We observed that these two lipids were largely miscible at all pH values and in the presence and absence of the polypeptides. However, there was some increased tendency for phase separation at higher pH and in the absence of polypeptide. Thus neither changes in curvature strain nor lateral phase separation induced by the polycationic amino acids could account for their marked ability to induce leakage and fusion. Phosphatidylethanolamine labelled with pyrene on one of the acyl chains gives rise to fluorescent emission from both monomer and excimer forms. The ratio of emission intensity from these two forms is indicative of lateral phase separation and the degree of lateral mobility of this probe. In equimolar mixtures of the 1-palmitoyl-2-oleoyl forms of phosphatidylserine and phosphatidylethanolamine in the liquid crystalline phase at 30 degrees C we find little effect of pH on the ratio of excimer to monomer emission intensity. However poly-L-lysine markedly lowers the fraction of excimer emission from these liposomes through the pH range from 5 to 7. Poly-L-histidine lowers the excimer to monomer emission ratio at pH 5 but not at pH 7. This is opposite to what one would expect for lateral phase separation and is interpreted at being the consequence of the polypeptide lowering the rate of lateral diffusion of the lipids. This effect of poly-L-histidine is observed over a range of temperatures from 0 to 40 degrees C in both gel and liquid crystalline phases. There is no evidence from the behaviour of the pyrene fluorescent probe for lipid interdigitation.(ABSTRACT TRUNCATED AT 400 WORDS)

Calorimetry, Differential Scanning↗