Biomedical subjects

M F Leung

Publications and source records attributed to M F Leung.

At least 19 recordsLinked to original sources

PubMed2005

Clopidogrel-induced hepatotoxicity after percutaneous coronary stenting.

Clopidogrel, an adenosine diphosphate receptor blocker, is widely used as an adjunctive antiplatelet therapy in acute coronary syndrome and percutaneous coronary stenting. The occurrence of hepatotoxicity is rare. We describe the occurrence of symptomatic liver disease in a 74-year-old man 5 weeks following commencement of therapy with clopidogrel. The reported cases of clopidogrel-induced hepatotoxicity are reviewed and the clinical significance of this event are discussed.

Aged↗

PubMed2003

Risk modeling, assessment, and management of lahar flow threat.

The 1991 eruption of Mount Pinatubo in the Philippines is considered one of the most violent and destructive volcanic activities in the 20th century. Lahar is the Indonesian term for volcanic ash, and lahar flows resulting from the massive amount of volcanic materials deposited on the mountain's slope posed continued post-eruption threats to the surrounding areas, destroying lives, homes, agricultural products, and infrastructures. Risks of lahar flows were identified immediately after the eruption, with scientific data provided by the Philippine Institute of Volcanology, the U.S. Geological Survey, and other research institutions. However, competing political, economic, and social agendas subordinated the importance of scientific information to policy making. Using systemic risk analysis and management, this article addresses the issues of multiple objectives and the effective integration of scientific techniques into the decision-making process. It provides a modeling framework for identifying, prioritizing, and evaluating policies for managing risk. The major considerations are: (1) applying a holistic approach to risk analysis through hierarchical holographic modeling, (2) applying statistical methods to gain insight into the problem of uncertainty in risk assessment, (3) using multiobjective trade-off analysis to address the issue of multiple decisionmakers and stakeholders in the decision-making process, (4) using the conditional expected value of extreme events to complement and supplement the expected value in quantifying risk, and (5) assessing the impacts of multistage decisions. Numerical examples based on ex post data are formulated to illustrate applications to various problems. The resulting framework from this study can serve as a general baseline model for assessing and managing risks of natural disasters, which the Philippines' lead agency-the National Disaster Coordinating Council (NDCC)-and other related organizations can use for their decision-making processes.

Journal Article↗

PubMed2000

IL-6 enhanced the retinoic acid-induced differentiation of human acute promyelocytic leukemia cells.

It has been shown that retinoic acid (RA) induced the expression of interleukin-6 (IL-6) in human acute promyelocytic leukemia HL-60 cells. In the present study, we examined the ability of RA to induce the expression of gp130, the signal-transducing receptor component for IL-6, in HL-60 and a RA-supersensitive cell line HL-60/S4. We found that RA induced the expression of gp130, at both the mRNA and protein levels, in HL-60 and HL-60/S4 cells. Interestingly, the induction of gp 130 expression observed in the RA-supersensitive HL-60/S4 cells was much more pronounced than that observed in HL-60 cells. Furthermore, activation of the RA-induced gp130 by exogenous IL-6 potentiated the differentiating effects of RA. The synergistic effects observed for IL-6 and RA was also much stronger in HL-60/S4 cells than in HL-60 cells. Our findings suggest that the differentiating effects of RA may partially be mediated by the up-regulation of IL-6/gp130 signaling in HL-60 and HL-60/S4 cells.

Antigens, CD↗

PubMed2000

Induction of TrkA expression by differentiation inducers in human myeloid leukemia KG-1 cells.

We have recently reported that retinoic acid (RA) induced the expression of trkA, the high affinity receptor for nerve growth factor (NGF), in human myeloid leukemia KG-1 cells. In the present study, we report that the expression of trkA was also induced by several other differentiation inducers, including 1alpha, 25-dihydroxyvitamin D3 (Vit D3), 1-beta-D-arabinofuranosyl cytosine (Ara-C), sodium butyrate (NaBut), and phorbol 12-myristate 13-acetate (PMA). Interestingly, RA in combination with NaBut or PMA synergistically induced cellular differentiation as well as the expression of trkA in KG-1 cells. Furthermore, activation of the induced trkA receptor by exogenous NGF potentiated the differentiating effects of RA and NaBut. Our results demonstrated that the induction of trkA is an event associated with the differentiation of KG-1 cells. Our findings suggest that NGF, in addition to its pivotal roles in the nervous system, may also play important roles in hematopoietic differentiation.

Butyrates↗

PubMed2000

Differential gene expression of hepatocellular carcinoma using cDNA microarray analysis.

A cDNA microarray technique, which allows simultaneous analysis of differential expression of mRNA of over 4000 known human genes, was utilized to study the gene expression in 10 pairs of HCC and nontumorous tissues from ethnic Chinese patients in Hong Kong. A total of 211 genes were found to be highly expressed and 147 genes were downregulated in more than 1 out of 10 of the HCC pairs. The results were significant by two-tailed Wilcoxon test (P < or = 0.05 with 95% confidence) on the intensity of each DNA spot of the 10 HCC pairs. Six genes were highly expressed and 10 genes were downregulated in more than 30% of HCC pairs. Results are consistent with other published reports using traditional differential display, subtractive hybridization, or immunohistochemical staining methods. We also detected that beta-actin and glyceraldehyde 3-phosphate dehydrogenase (G3PDH), which have been commonly used as an internal standard control in mRNA expression studies, were highly expressed in HCC when compared with nontumorous tissue. It is concluded that cDNA microarray analysis is an effective method in the detection of differential gene expression in HCC.

Actins↗

PubMed1999

Induction of gp130 and LIF by differentiation inducers in human myeloid leukemia K562 cells.

It has been previously shown that phorbol 12-myristate 13-acetate (PMA), a potent differentiation inducer, induced the expression of both interleukin-6 (IL-6) and IL-6 receptor alpha component (IL-6Ralpha) in K562 leukemia cells. In the present study, we examined the ability of several differentiation inducers to regulate the expression of the signal-transducing receptor component for IL-6, gp130, and cytokine leukemia inhibitory factor (LIF) in K562 cells. We found that the expression of gp130 was dramatically induced at both the mRNA and protein levels by the two megakaryocytic inducers sodium butyrate (NaBut) and PMA. In contrast, the mRNA expression of LIF was induced by the two erythroid inducers 1-beta-D-arabinofuranosyl cytosine (Ara-C) and hemin. Furthermore, activation of the PMA-induced gp130 receptor by exogenous IL-6 potentiated the differentiating effects of PMA. Our findings suggest that IL-6/gp130 signaling may be involved in the regulation of the megakaryocytic differentiation of K562 cells.

Antigens, CD↗

PubMed1999

The differentiating effect of retinoic acid and vincristine on acute myeloid leukemia.

We have shown previously that granulocytic maturation and differentiation occurred when HL-60 cells and leukemia cells from a patient with acute promyelocytic leukemia (APL) were exposed to all-trans retinoic acid (ATRA) after treatment with a noncytotoxic concentration of vincristine (VCR), suggesting that VCR might have synergistic action with ATRA in the treatment of APL. Leukemic cells obtained from 24 patients with AML were exposed to 20 nM VCR for 1 h, followed by 1 microM ATRA for 6 days. Changes in the expression of myeloid leukocyte antigens were observed using flow cytometry. Differentiation phenotype as determined by the decrease or increase in maturation cell marker was observed in three samples treated with VCR alone, four samples treated with RA alone, and two samples treated with the combination of VCR and RA. The results suggest that treatment using VCR and ATRA may be effective in the differentiation therapy of AML.

Acute Disease↗

PubMed1998

Induction of NG108-15 cells differentiation by human bone marrow stromal cells.

The survival and differentiation of neuronal cells is dependent on factors such as neurotrophins, cytokines and components of extracellular matrix. Bone marrow stromal cells have been shown to support the growth and differentiation of neuroblastoma cells. In an attempt to study the effects of bone marrow stromal cells on neuronal differentiation, we have co-cultured neuroblastoma x glioma hybrid NG108-15 cells with human bone marrow stromal cells. After co-culturing, clones exhibiting morphological differentiated phenotype and high level of neurofilament expression were isolated. Interestingly, these clones maintain their ability to proliferate in contrast to differentiated NG108-15 cells induced by dibutyryladenosine 3',5'-cyclic monophosphate. These results suggested that bone marrow stromal cells can induce partial differentiation of NG108-15 cells.

Animals↗

PubMed1998

Genetic and environmental risk factors for Parkinson's disease in a Chinese population.

An epidemiological study of the environmental and genetic factors as well as the possible interplay between them was conducted among 215 patients with Parkinson's disease and 313 controls in a Chinese population in Hong Kong. In univariate analysis, a regular tea drinking habit was found to be a protective factor, which had not been reported before. Smoking (a protective factor), family history, duration of pesticide exposure (in years) in farming and pesticide exposure during farming in women (both risk factors) have been reported previously. In multivariate analysis, current smoking reached borderline significance at the 5% level and the variables, years exposed to pesticides and family history were significant at the 10% level. By contrast with the common occurrence of polymorphism of the CYP2D6 gene (a gene involved with xenobiotic metabolism) in white people, it is very rare in China and is not thought to be a significant factor contributing to Parkinson's disease in Chinese people.

Aged↗

PubMed1997

Induction of TrkA receptor by retinoic acid in leukaemia cell lines.

To explore the potential involvement of neurotrophins in the actions of retinoic acid (RA) on leukaemia differentiation, we examined the ability of RA to regulate the expression of neurotrophins and Trk receptors in several leukaemia cell lines. Expression of TrkA was dramatically induced by RA at both the mRNA and protein level in leukaemia cell lines K562 and KG-1. Furthermore, while no expression of trkB and trkC was detected, constitutive expression of nerve growth factor (NGF), neurotrophin-3 and neurotrophin-4/5 could be detected in leukemia cells. Our findings suggested that NGF/trkA may potentially be involved in the RA-induced differentiation of leukemia cells.

Antineoplastic Agents↗

PubMed1997

Intrinsic secondary structure of human TNFR-I mRNA influences the determination of gene expression by RT-PCR.

The secondary structure of human tumor necrosis factor receptor I (TNFR-I) mRNA based on its lowest folding energy was predicted. Three combinations of primers selected from open-regions and four combinations of primers from closed-regions of TNFR-I mRNA structure were employed for single-tube reverse transcription-polymerase chain reaction (RT-PCR) for the determination of TNFR-I gene expression in U937 cell. All the primers were designed with the same criteria. However, the different primers generated distinct quantities of RT-PCR products from the same concentration of TNFR-I mRNA, implying that the determination of gene expression by RT-PCR was affected by the mRNA secondary structure. In addition, the sensitivity of the open-region RT-PCR was approximately one hundred-fold higher than that in the closed-regions of TNFR-I mRNA. The low efficiency of the closed-region RT-PCR was not correlated with the G/C content of the TNFR-I mRNA structure. These results suggest that consideration of the influence of intrinsic mRNA structure of a gene is essential prior to the determination of gene expression by quantitative RT-PCR, and this open-region strategy of primer design may yield an efficient primer for in vitro amplification of cDNA by RT-PCR.

Antigens, CD↗

PubMed1996

Microtubule-dependent multilobular organization of the nucleus in sensitive and multidrug-resistant L0 leukemia cells.

The relationship between the nuclear morphology and the microtubular organization of L100 and L1000 cells, two vincristine-induced multidrug resistant human acute lymphocytic leukemia cell lines, was examined and compared to that of L0 parental cells. The L0 parental cells contained a round nucleus and the microtubules were evenly distributed throughout the cytoplasm. In contrast, the microtubules of the L100 and L1000 cells were localized between the lobular structures of a multilobulated nucleus. Disassembly of microtubules in L100 and L1000 cells by colchicine resulted in the loss of the multilobulated morphology of the nucleus. While the total cellular content of tubulin of L0 and L100 cells was similar, the content of microtubules of L100 cells was only 55% of that observed in L0 cells. Two, 28 kDa (pI 6.9) and 31 kDa (pI 4.4), microtubule-associated proteins were found to be overexpressed in L100 and L1000 cells. The results indicate that the multilobulated nuclear morphology of L100 and L1000 cells is dependent upon the unique and intact organization of the microtubules; the distinct organization of the microtubules and the multilobular nuclear morphology of the two resistant cell lines may be due to the differential expression of specific microtubule-associated proteins.

Cell Cycle↗

PubMed1996

Induction of trk receptors by retinoic acid in a human embryonal carcinoma cell line.

Retinoic acid induced the differentiation of human embryonal carcinoma cells (NT2/D1) into several morphologically distinct cell types, including those resembling terminally differentiated postmitotic CNS neurones. The mechanism by which retinoic acid influences the process of neuronal differentiation in the CNS, however, remains unknown. In the present study, we have examined the ability of retinoic acid to induce the expression of the receptors that mediate the actions of the neurotrophins, using reverse transcription-polymerase chain reaction and Northern blot analysis. Our study demonstrated that the expression of mRNAs for three human trk receptors was significantly induced after treatment with retinoic acid. These findings suggest that the actions of retinoic acid on neuronal differentiation in the human CNS may potentially be mediated by the neurotrophins.

Antineoplastic Agents↗

PubMed1996

In vitro amplification of human basic fibroblast growth factor mRNA by RNA-specific exon-junction primers.

Highly sensitive and RNA-specific primers for the determination of human basic fibroblast growth factor (bFGF) gene expression by RT-PCR were identified. The RNA-specific primers could amplify bFGF mRNA from 10 pg to 1 ng of total cellular RNA without interfering with the presence of genomic DNA of the cell. The feasible temperatures of the primers annealed to the template were 55 degrees C, 60 degrees C and 65 degrees C. In addition, different locations of primers on the bFGF mRNA molecule yielded distinct amounts of RT-PCR products from the same concentration of RNA, suggesting that the mRNA secondary structure of bFGF affected the RT-PCR. Owing to high sensitivity and specificity of the primers to bFGF RNA, the RNA-specific primers may be potentially utilized for the determination of human bFGF gene expression by in situ RT-PCR.

Base Sequence↗

PubMed1996

Identification and characterization of an RNA specific primer for human tumor necrosis factor receptor I (TNFR-I).

An RNA specific primer amplified TNFR-I cDNA from cellular RNA by single-tube (ST) RT-PCR without interfering with the presence of genomic DNA of cell was identified. The primer detected TNFR-I from 1 ng of cellular RNA by ST RT-PCR, and was not cross-reacted with TNFR-II despite of the homologous sequence between TNFR-I and -II. In addition, the mechanism of the RNA specificity of the primer was investigated. An intron of 0.43 kb was inserted in the 5'-925 of TNFR-I mRNA sequence. The result corresponded with the previous determination of TNFR-I gene structure. Thus, it appears that the RNA specificity of the primer might be resulted from the antisense primer hybridizing to exon-intron junction. Owing to its high sensitivity and specificity to TNFR-I RNA, the RNA specific primer may be potentially utilized for the determination of human TNFR-I gene expression by in situ RT-PCR.

Antigens, CD↗

PubMed1992

Changes in actin and actin-binding proteins during the differentiation of HL-60 leukemia cells.

Actin and actin-binding proteins form a peripheral network on the cytosolic side of the plasma membrane. These cytoskeleton proteins are involved in functions that require cellular movement and may also have a role in modulating signal transduction during cellular proliferation and differentiation. To measure changes in F-actin and actin-binding proteins during HL-60 differentiation, cells were induced to mature along the granulocytic pathway by exposure to 1 microM retinoic acid (RA) for 5 days and were analyzed for F-actin and actin-binding proteins by flow cytometry. The amounts of F-actin and spectrin in untreated HL-60 cells and in those undergoing differentiation by treatment with the retinoid did not differ. N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)-phallacidin was used to measure F-actin content and a monoclonal antibody followed by fluorescence isothiocyanate-conjugated goat anti-mouse immunoglobulin antibody was used to measure the content of spectrin; cells were analyzed by flow cytometry. In contrast, cells exposed to RA contained larger amounts of alpha-actinin, vinculin, talin, lipocortin I, and lipocortin II, as determined with their respective antibodies followed by flow cytometric analysis as described above. An RA-supersensitive clone of HL-60, designated HL-60/S4, exhibited lower constitutive levels of alpha-actinin, vinculin, and talin but a higher constitutive level of lipocortin II than parental cells. Treatment of HL-60/S4 with RA led to increases in vinculin, talin, lipocortin I, and lipocortin II. An RA-resistant clone, designated HL-60/R3, constitutively expressed larger amounts of alpha-actinin, vinculin, lipocortin I, and lipocortin II than parental HL-60 cells. Treatment of HL-60/R3 with RA resulted in decreases in the amounts of these actin-binding proteins. Changes in actin-binding proteins that occur during the differentiation of HL-60 cells suggest that these proteins may be of importance to the expression of the mature phenotype.

Actinin↗

PubMed1992

Changes in microtubules, microtubule-associated proteins, and intermediate filaments during the differentiation of HL-60 leukemia cells.

The cytoskeleton is composed mainly of microtubules (MT), microfilaments, and intermediate filaments (IF) that form a structural network which connects cellular membranes, cytoplasmic organelles, and the nucleus. Since the cytoskeleton may be involved in modulating signal transduction and in the morphological and structural changes that occur during cellular proliferation and differentiation, cytoskeletal changes were measured by immunofluorescence microscopy and fluorescence-activated cell sorter analysis during the differentiation of HL-60 leukemia cells induced by retinoic acid (RA). Differentiated HL-60 cells exhibited increased staining intensity and altered organization of MT and IF, as visualized by immunofluorescence microscopy with anti-tubulin monoclonal antibody and anti-vimentin antibody, respectively. A new procedure was developed and used to measure the content of the cytoskeletal components of HL-60 cells during the process of maturation. HL-60 cells were fixed with formaldehyde in an MT-stabilizing buffer, permeabilized using L-lysophosphatidylcholine, stained for immunofluorescent measurement with antibodies specific for particular cytoskeletal components, and analyzed by flow cytometry. Terminally differentiated cells produced by exposure to RA contained larger amounts of MT and the IF vimentin. During the course of the maturation process, a transient increase in the amounts of the microtubule-associated proteins, (MAPs) MAP2 and tau, occurred. An RA-supersensitive clone, designated HL-60/S4, and an RA-resistant clone, designated HL-60/R3, were developed by mutagenization and selection. Use of these clones supported the concept that the observed changes in MT, MAPs, and vimentin were associated with the differentiation process rather than being due to other effects produced by the retinoid. Thus, the findings suggest that changes in MT, MAPs, and IF are important to the terminal maturation of leukemia cells.

Cell Differentiation↗

PubMed1992

The effects of microtubule disrupting drugs on the differentiation of HL-60 leukemia cells.

We and others have previously shown that microtubules (MT) are stained more intensely and are organized differently in differentiating leukemia cells. To study the effects of the MT disrupting drugs, colchicine (Coln) and vincristine (VCR), on the maturation process, HL-60 leukemia cells were pretreated with Coln or VCR for 1 h and then exposed to either retinoic acid (RA) or dimethyl sulfoxide (DMSO). Neither Coln nor VCR induced the differentiation of HL-60 cells, but in combination with RA increased the percentage of nitroblue tetrazolium-positive cells, the expression of the mature myelocyte surface marker Mo 1, and the content of MT over the effects produced by RA alone. In contrast, pretreatment with Coln or VCR delayed the commitment to a differentiation pathway induced by DMSO. The supra-additivity exhibited between Coln and RA required the administration of Coln prior to RA; thus, Coln had no effect when given two days after the cellular exposure to RA. The findings suggest that (a) a combination of non-cytotoxic concentrations of Coln or VCR with RA may have clinical utility as inducers of leukemia cell maturation, and (b) MT may be involved in modulating signal transduction during the initiation of HL-60 cell differentiation.

Cell Differentiation↗