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Biomedical subjects

W M Li

Publications and source records attributed to W M Li.

At least 19 recordsLinked to original sources
PubMed2002

Controlling the physical behavior and biological performance of liposome formulations through use of surface grafted poly(ethylene glycol).

The presence of poly(ethylene glycol) (PEG) at the surface of a liposomal carrier has been clearly shown to extend the circulation lifetime of the vehicle. To this point, the extended circulation lifetime that the polymer affords has been attributed to the reduction or prevention of protein adsorption. However, there is little evidence that the presence of PEG at the surface of a vehicle actually reduces total serum protein binding. In this review we examine all aspects of PEG in order to gain a better understanding of how the polymer fulfills its biological role. The physical and chemical properties of the polymer are explored and compared to properties of other hydrophilic polymers. An evidence based assessment of several in vitro protein binding studies as well as in vivo pharmacokinetics studies involving PEG is included. The ability of PEG to prevent the self-aggregation of liposomes is considered as a possible means by which it extends circulation longevity. Also, a "dysopsonization" phenomenon where PEG actually promotes binding of certain proteins that then mask the vehicle is discussed.

Adsorption↗
PubMed2001

Indoor air quality at restaurants with different styles of cooking in metropolitan Hong Kong.

Indoor air quality (IAQ) of a restaurant has increasingly received a lot of public concerns in Hong Kong. Unfortunately, there is limited data about the IAQ of Hong Kong restaurants. In order to characterize the current IAQ of local restaurants, four restaurants in metropolitan Hong Kong including a Korean barbecue style restaurant, a Chinese hot pot restaurant, a Chinese dim sum restaurant and a Western canteen were selected for this study. The results of this study showed that the mean concentrations of CO2 at restaurants with gas stoves for food cooking in dining areas exceeded the range from 40 to 60% indoor CO2 concentrations at restaurants without gas stoves in dining areas. The average levels of PM10 and PM2.5 at the Korean barbecue style restaurant were as high as 1442 and 1167 microg/m3, respectively. At the Korean barbecue and Chinese hot pot restaurants, the levels of PM2.5 accounted for 80-93% of their respective PM10 concentrations. The 1-h average levels of CO observed at Korean barbecue style and hot pot restaurants were 15,100 and 8000 microg/m3, respectively. Relatively high concentrations of CO2, CO, PM10, PM2.5 benzene, toluene, methylene chloride and chloroform were measured in the dining areas of the Korean barbecue style and the Chinese hot pot restaurants. The operations of pan-frying food and boiling food with soup in a hot pot could generate considerable quantities of air pollutants.

Air Pollution, Indoor↗
PubMed2001

Multiple genetic changes are associated with mammary tumorigenesis in Brca1 conditional knockout mice.

Germline mutations in the tumor suppressor gene BRCA1 predispose women to breast cancer, however somatic mutations in the gene are rarely detected in sporadic cancers. To understand this phenomenon, we examined mouse models carrying conditional disruption of Brca1 in mammary epithelium in either p53 wild type (wt) or heterozygous backgrounds. Although a p53(+/-) mutation significantly accelerated tumorigenesis, both strains developed mammary tumors in a stochastic fashion, suggesting that multiple factors, in addition to p53 mutations, may be involved in Brca1 related tumorigenesis. A unique feature of Brca1 mammary tumors is their highly diverse histopathology accompanied by severe chromosome abnormalities. The tumors also display extensive genetic/molecular alterations, including overexpression of ErbB2, c-Myc, p27 and Cyclin D1 in the majority of tumors, while they were virtually ERalpha and p16 negative. Translocations involving p53 were also identified which lead to abnormal RNA and protein products. In addition, we generated cell lines from mammary tumors and found that the cells retained many of the genetic changes found in the primary tumors, suggesting that these genes may be players in Brca1-associated tumorigenesis. Despite their distinct morphology, all cultured tumor cells were Tamoxifen resistant but highly sensitive to Doxorubicin or gamma-irradiation, suggesting that these methods would be effective in treatment of this disease.

Animals↗
PubMed2001

Enhanced immune response to T-independent antigen by using CpG oligodeoxynucleotides encapsulated in liposomes.

Immunostimulatory CpG oligodeoxynucleotides (ODN) have been tested as immunoadjuvants for various vaccines including T-cell independent (TI) antigens. Findings from previous reports suggest that close physical association of CpG ODN to the antigen could enhance its adjuvant effect. As an alternative to chemical conjugation of CpG ODN to the antigen, the current study is aimed at determining the benefit of using liposomes as a carrier for CpG ODN to improve the immune response to biotinylated liposomes (Bx-liposomes), a model of a TI antigen. Liposomes with suboptimal concentration of hapten (1% biotin) were not immunogenic. However, when CpG ODN encapsulated in Bx-liposomes were used to immunize mice, a hapten-specific response was obtained as indicated by antibody-mediated elimination of re-administered Bx-liposomes. CpG ODN co-administered with empty Bx-liposomes could not achieve the same effect, indicating the requirement for encapsulation of the adjuvant. Using both intravenous (i.v.) and subcutaneous (s.c.) immunization methods, it was found that IgM levels, but not IgG levels were elevated. Immunization in nude mice confirmed that the immune response obtained was TI. The use of non-CpG ODN and an ODN with alternatively flanked CpG motifs showed no adjuvant effect. Incorporation of poly(ethylene)glycol (PEG)-modified lipid in liposomes enhanced the immune response even further. In conclusion, our data shows that liposomes are a useful delivery vehicle for CpG ODN as an immune adjuvant for TI antigens.

Adjuvants, Immunologic↗
PubMed2001

Intermembrane transfer of polyethylene glycol-modified phosphatidylethanolamine as a means to reveal surface-associated binding ligands on liposomes.

In order to explore the use of exchangeable poly(ethylene glycol) (PEG)-modified diacylphosphatidylethanolamines (PE) to temporarily shield binding ligands attached to the surface of liposomes, a model reaction based on inhibition and subsequent recovery of biotinylated liposome binding to streptavidin immobilized on superparamagnetic iron oxide particles (SA magnetic particles) was developed. PEG-lipid incorporation into biotinylated liposomes decreased liposome binding to SA magnetic particles in a non-linear fashion, where as little as 0.1 mol% PEG-PE resulted in a 20% decrease in binding. Using an assay based on inhibition of binding, PEG(2000)-PE transfer from donor liposomes to biotinylated acceptor liposomes could be measured. The influence of temperature and acyl chain composition on the transfer of PEG-diacyl PEs from donor liposomes to acceptor liposomes, consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine, cholesterol and N-((6-biotinoyl)amino)hexanoyl)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (54.9:45:0.1 mole ratio), was measured. Donor liposomes were prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (50 mol%), cholesterol (45 mol%) and 5 mol% of either PEG-derivatized 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE-PEG(2000)), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE-PEG(2000)), or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE-PEG(2000)). Transfer of DSPE-PEG(2000) to the donor liposomes was not detected under the conditions employed. In contrast, DMPE-PEG(2000) was transferred efficiently even at 4 degrees C. Using an acceptor to donor liposome ratio of 1:4, the time required for DMPE-PEG(2000) to become evenly distributed between the two liposome populations (T(EQ)) at 4 degrees C and 37 degrees C was approx. 2 and <0.5 h, respectively. An increase in acyl chain length from C14:0 to C16:0 of the PEG-lipid resulted in a significant reduction in the rate of transfer as measured by this assay. The transfer of PEG-lipid out of biotinylated liposomes was also studied in mice following intravenous administration. The relative rates of transfer for the various PEG-lipids were found to be comparable under in vivo and in vitro conditions. These results suggest that it is possible to design targeted liposomes with the targeting ligand protected while in the circulation through the use of PEG-lipids that are selected on the basis of exchange characteristics which result in exposure of the shielded ligand following localization within a target tissue.

Animals↗
PubMed2001

Indoor air quality at nine shopping malls in Hong Kong.

Hong Kong is one of the most attractive shopping paradises in the world. Many local people and international tourists favor to spend their time in shopping malls in Hong Kong. Good indoor air quality is, therefore, very essential to shoppers. In order to characterize the indoor air quality in shopping malls, nine shopping malls in Hong Kong were selected for this study. The indoor air pollutants included carbon dioxide (CO2), carbon monoxide (CO), total hydrocarbons (THC), formaldehyde (HCHO), respirable particulate matter (PM10) and total bacteria count (TBC). More than 40% of the shopping malls had 1-h average CO2 levels above the 1000 ppm of the ASHRAE standard on both weekdays and weekends. Also, they had average weekday PM10 concentrations that exceeded the Hong Kong Indoor Air Quality Objective (HKIAQO). The highest indoor PM10 level at a mall was 380 microg/m3. Of the malls surveyed, 30% had indoor airborne bacteria levels above 1000 cfu/m3 set by the HKIAQO. The elevated indoor CO2 and bacteria levels could result from high occupancy combined with insufficient ventilation. The increased PM10 levels could be probably attributed to illegal smoking inside these establishments. In comparison, the shopping malls that contained internal public transport drop-off areas, where vehicles were parked with idling engines and had major entry doors close to heavy traffic roads had higher CO and PM10 indoor levels. In addition, the extensive use of cooking stoves without adequate ventilation inside food courts could increase indoor CO2, CO and PM10 levels.

Air Pollution, Indoor↗
PubMed2001

Genetic interactions between tumor suppressors Brca1 and p53 in apoptosis, cell cycle and tumorigenesis.

Breast cancer is a chief cause of cancer-related mortality that affects women worldwide. About 8% of cases are hereditary, and approximately half of these are associated with germline mutations of the breast tumor suppressor gene BRCA1 (refs. 1,2). We have previously reported a mouse model in which Brca1 exon 11 is eliminated in mammary epithelial cells through Cre-mediated excision. This mutation is often accompanied by alterations in transformation-related protein 53 (Trp53, encoding p53), which substantially accelerates mammary tumor formation. Here, we sought to elucidate the underlying mechanism(s) using mice deficient in the Brca1 exon 11 isoform (Brca1Delta11/Delta11). Brca1Delta11/Delta11 embryos died late in gestation because of widespread apoptosis. Unexpectedly, elimination of one Trp53 allele completely rescues this embryonic lethality and restores normal mammary gland development. However, most female Brca1Delta11/Delta11 Trp53+/- mice develop mammary tumors with loss of the remaining Trp53 allele within 6-12 months. Lymphoma and ovarian tumors also occur at lower frequencies. Heterozygous mutation of Trp53 decreases p53 and results in attenuated apoptosis and G1-S checkpoint control, allowing Brca1Delta11/Delta11 cells to proliferate. The p53 protein regulates Brca1 transcription both in vitro and in vivo, and Brca1 participates in p53 accumulation after gamma-irradiation through regulation of its phosphorylation and Mdm2 expression. These findings provide a mechanism for BRCA1-associated breast carcinogenesis.

Animals↗
PubMed2001

The topography of quantified electroencephalography in three syndromes of schizophrenia.

This study investigated the association between quantified electroencephalography (qEEG) and three psychopathological syndromes, derived by a factor analysis of the symptom profile of a group of 40 subjects diagnosed with schizophrenia. An initial comparison with aged and sex matched normal controls showed an overall increase in slow wave activity in subjects with schizophrenia. The symptomatology of the subjects with schizophrenia was then factor analysed into three psychopathological syndromes that closely resembled Liddle's (1987b) original delineation. Correlations were undertaken between the three syndrome scores and qEEG. The "psychomotor poverty" factor was associated with increased beta activity most marked posteriorly and increased delta activity (accounted for by the effects of medication). The "disorganisation" factor was associated with widespread negative correlations in the alpha and beta bands and the "reality distortion" factor was associated positively with left anterior alpha activity. These distinct patterns of qEEG that clearly differentiate between the three syndromes, may contribute towards elucidating the underlying pathophysiological processes in schizophrenia. The results support the use of symptom based syndromes in reducing the diversity of findings in schizophrenia.

Adolescent↗
PubMed2001

[The primary role of central region of HC-pro of potato Y potyvirus in synergism of plant viruses].

Five deleted mutants of HC-Pro gene of Chinese isolate of potato Y potyvirus (PVY-C) were obtained by PCR mutation, and their plant expression vectors were constructed. They were transformed into tobacco K326 (Nicotina tabacum cv. K326) mediated by Agrobacterium. PCR and Southern blot analysis revealed that PVY-C HC-Pro gene and its deleted mutants were integrated into tobacco genome, and Western blot analysis showed that they were all expressed in transgenic tobacco plants. Furthermore, infection test demonstrated that the central region of PVY-C HC-Pro can mediate synergism of PVY-C/cucumber mosaic cucumovirus (CMV) and PVY-C/potato X potexvirus (PVX), identifying that it is functional domain in synergism.

Blotting, Southern↗
PubMed2000

[Effects of serum-free murine bone marrow endothelial cell conditioned medium on the growth of CFU-E and BFU-E].

Serum-free murine bone marrow endothelial cell conditioned medium(mBMEC-cm) was collected. The mBMEC-cm was ultrafiltered in Centriprep. The concentrated retentive substance of mBMEC-cm (MW > 10,000) and filtrate of mBMEC-cm(MW < 10,000) were obtained. The effects of mBMEC-cm on the growth of CFU-E and BFU-E were investigated. The results showed: 1. The retentive substance of mBMEC-cm significantly enhanced the growth of CFU-E and BFU-E. The effects of mBMEC-cm(2%-6%, V/V) on the growth of CFU-E and BFU-E were dose-dependent. 2. The filtrate of mBMEC-cm markedly inhibited the growth of CFU-E and BFU-E. The effects of the filtrate of mBMEC-cm on the growth of CFU-E and BFU-E were also dose-dependent. The mechanism of regulation will be studied further.

Animals↗
PubMed2000

Positive and negative hematopoietic cytokines produced by bone marrow endothelial cells.

Recently, cytokines and interleukins such as SCF, GM-CSF, G-CSF, TGF-beta, IL-6, IL-7, IL-8, IL-11 have been reported to be elaborated by endothelial cells. For further study, serum free bone marrow endothelial cell conditioned medium (BMEC-CM) was collected and ultrafiltrated by using a centriprep 10. The concentrated retentate (R-BMEC-CM) contained some substances whose molecular weight was more than 10 000 daltons. The filtrate (F-BMEC-CM) contained some substances whose molecular weight was less than 10 000 daltons. The effects of R-BMEC-CM and F-BMEC-CM on the growth of haematopoietic progenitors and the expression of cytokine and interleukin mRNAs of BMEC were investigated. The results showed that R-BMEC-CM stimulated the growth of CFU-GM, HPP-CFC, BFU-E, CFU-E, and CFU-Meg; while F-BMEC-CM inhibited the growth of these progenitors. Using the method of hybridizing to the Atlas cDNA Array, we were able to detect the presence of mRNAs of cytokines and interleukins in bone marrow endothelial cells. Our finding of the existence of mRNAs of SCF, GM-CSF, IL-6, TGF-beta, IL-1, and IL-11 in these cells was in agreement with the data reported previously. Furthermore, we detected mRNAs of MIP-2, Thymosion-beta4, PDGF, MSP-1, IFN-gamma, IL-13 and inhibin, which are related to haematopoiesis. Among these cytokines and interleukins, SCF, GM-CSF, IL-6, IL-1, and IL-11 are haematopoietic stimulators which may be responsible for the stimulative effects on the growth of haematopoietic progenitors. One of our new findings, the thymosin-beta4, is a small molecular haematopoietic inhibitor. It may be responsible for the inhibitory effect of F-BMEC-CM on haematopoietic progenitors. The presence of mRNAs of BMP, MSP-1, MIP-2, PDGF and IL-13 suggests that bone marrow endothelial cells might elaborate these substances. Their influence on haematopoietic progenitors needs further study.

Animals↗
PubMed2000

[The effects of cytokines produced by bone marrow endothelial cells on the regulation of hematopoiesis].

In this study, the effects of bone marrow endothelial cell conditioned medium (BMEC-CM) on hematopoietic progenitors and the expression of cytokines mRNA of BMEC were investigated. BMEC-CM was ultrafiltrated in Centriprep-10, an ultrafiltering concentrator. The retentate (MW>10 kD) and filtrate (MW<10 kD) were obtained. The effects of different components of BMEC-CM on the murine hematopoietic progenitors were examined. The results showed that the retentate of BMEC-CM (MW>10 kD) significantly promoted the growth of CFU-GM, CFU-E, BFU-E, CFU-Meg and HPP-CFC, while the growth of CFU-GM, CFU-E, BFU-E, CFU-Meg and HPP-CFC were markedly inhibited by the filtrate of BMEC-CM (MW<10 kD). The effects of BMEC-CM were dose-dependent. The presence of mRNAs for GM-CSF, TGF-beta, bone morphogenetic protein 2A, basic fibroblast growth factor receptor, endothelin-2, macrophage-stimulating 1 (MSP-1), thymosin-beta10, connective tissue growth factor, macrophage inflammatory protein 2 alpha (MIP-2alpha), IL-6, IL-11, IL-13 and IFN-gamma mRNA were successfully detected by Atlas Arrays.

Animals↗
PubMed1999

Electrodermal activity in schizophrenia: a quantitative study using a short interstimulus paradigm.

BACKGROUND: Electrodermal activity in response to short interstimulus interval (ISI) stimulation allows aspects of information processing to be examined, but such paradigms cause skin conductance responses (SCRs) to overlap. A signal decomposition method was developed and employed to score the overlapped SCRs. This is the first application of the method to the study of schizophrenia. METHODS: Electrodermal activity of 30 medicated patients with schizophrenia and 50 normal controls was obtained using a conventional auditory oddball paradigm with an ISI of 1.3 sec. Tonic skin conductance level (SCL), phasic SCRs, SCR temporal dynamics, and a range of SCR variables in response to target tones were examined. RESULTS: The schizophrenic group showed reduced response rate, proportion of responders, SCR amplitude, rise time, peak latency, and steady-state response amplitude, over the trial compared with controls. There were no between-group differences in SCL or SCR onset time. CONCLUSIONS: The combined use of a conventional short ISI paradigm and the new SCR scoring method demonstrated new facets of electrodermal hyporeactivity in medicated patients with schizophrenia. The hyporeactivity could not be attributed to changes in tonic arousal or dysfunctions in peripheral sympathetic nerve conductance.

Acoustic Stimulation↗
PubMed1999

Acute and chronic oral administration of bis(maltolato)oxovanadium(IV) in Zucker diabetic fatty (ZDF) rats.

This is a preliminary study in which both acute and chronic oral administration of bis(maltolato)oxovanadium (IV) (BMOV) was examined in the Zucker diabetic fatty (ZDF) rat, an animal model that develops overt hyperglycemia in the presence of hyperinsulinemia followed by beta-cell depletion. At 9-10 weeks of age, in the presence of hyperglycemia, hyperinsulinemia and hyperlipidemia, an acute oral gavage dose response was conducted to determine glucose-lowering properties of BMOV, time of response and effect of BMOV on plasma insulin levels. Doses of BMOV greater than 0.2 mmol/kg resulted in plasma glucose levels of less than 9 mmol/l. The highest dose administered (0.8 mmol/kg) significantly reduced plasma insulin (initial: 2.83+/-0.2, final: 1.23+/-0.09 nmol/l, P<0.05) and plasma triglyceride (initial: 4.94+/-0.33, final: 1.55+/-0.07 mmol/l, P<0.05) levels. At 15 weeks of age, in the presence of hyperglycemia, hyperlipidemia and normal insulin levels, BMOV was administered orally in the drinking water for a 10-week period to determine the effect of treatment on glucose, insulin and lipid levels. BMOV treatment significantly reduced plasma glucose levels (final BMOV-treated: 13.25+/-1.43, untreated: 28.71+/-0.6 mmol/l, P<0.05) and effectively preserved pancreatic beta-cell function. These data suggest a role for BMOV as a therapeutic agent in non-insulin-dependent diabetes mellitus through improvement in glucose homeostasis and preservation of insulin reserves.

Administration, Oral↗
PubMed1999

Time-related mapping of quantitative trait loci underlying tiller number in rice.

Using time-related phenotypic data, methods of composite interval mapping and multiple-trait composite interval mapping based on least squares were applied to map quantitative trait loci (QTL) underlying the development of tiller number in rice. A recombinant inbred population and a corresponding saturated molecular marker linkage map were constructed for the study. Tiller number was recorded every 4 or 5 days for a total of seven times starting at 20 days after sowing. Five QTL were detected on chromosomes 1, 3, and 5. These QTL explained more than half of the genetic variance at the final observation. All the QTL displayed an S-shaped expression curve. Three QTL reached their highest expression rates during active tillering stage, while the other two QTL achieved this either before or after the active tillering stage.

Chromosome Mapping↗
PubMed1999

Dynamics of SCR, EEG, and ERP activity in an oddball paradigm with short interstimulus intervals.

Studies of concurrent central, and autonomic activity using a conventional event-related potential (ERP) oddball paradigms, are considered useful in elucidating the relationship between central and autonomic responses, but the autonomic response tends to overlap. A new method was used to decompose and score overlapping skin conductance responses (SCR). This method enabled examination of dynamic relationships of phasic SCR, prestimulus electroencephalogram (EEG), and ERP to auditory target stimuli in 50 normal adults. SCR amplitude was negatively correlated to EEG and N200 amplitude. The SCR amplitude changes over time exhibited an exponential decline opposite to those of N200, alpha, and beta. All the fitted exponential functions had a time constant of 1-2 min. The findings suggest that a N200 component, active in the auditory sensory discrimination, is concomitant with the SCR. The narrow range of the time constant may provide a clue to the conjoint processes underlying central and autonomic adaptive functions.

Adult↗
PubMed1998

Late components of the event-related potentials and their topography in Parkinson's disease.

Late components of the event-related potential (ERP; N100, P200, N200, and P300) were elicited using an auditory oddball paradigm (with a button-press response to target stimuli) in 15 Parkinson's disease (PD) patients and 50 normal control subjects. Compared with control subjects, PD subjects showed a significant decrease in N200 amplitude. Between-group topographical differences in N200 amplitude were evident at central (C3, Cz, C4) and temporal (T5, T3, T4, T6) regions. The results may reflect a deficit in response selection in PD possibly resulting from a dysfunction associated with the abnormalities in the central and temporal regions found to have a decreased N200 amplitude compared with normal control subjects in this study.

Acoustic Stimulation↗