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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

Reflex inhibition of heart rate and efferent cardiac sympathetic outflow induced by colorectal distension in anesthetized rats.

Colorectal distensions of 60 and 80 mmHg significantly reduced heart rate (HR) and cardiac sympathetic nerve activity in anesthetized rats. This bradycardiac response was not influenced by the intravenous administration of atropine, but was abolished by propranolol, suggesting that it was elicited by sympathetic but not vagal efferent nerves.

Adrenergic beta-Antagonists↗

Responses of blood pressure and renal sympathetic nerve activity to colorectal distension in anesthetized rats.

We investigated the effects of visceral stimulation by colorectal distension (CRD) on mean arterial blood pressure (MAP) and renal sympathetic nerve activity (RSNA), the latter being an index of vasoconstrictor activity, in anesthetized central nervous system (CNS)-intact and C2 spinalized rats. The CRD stimulation was induced by the distention of a balloon inserted into the colorectum. In CNS-intact rats, there were significant reductions in MAP and RSNA in response to intraballoon pressures of 60 and 80 mmHg, but not to 20 and 40 mmHg. However, spinalized rats demonstrated significant increases in MAP in response to intraballoon pressures of 60 and 80 mmHg and increases in RSNA in response to intraballoon pressures of 40, 60, and 80 mmHg. These results suggest that noxious visceral stimulation at lower spinal levels reduces MAP by inhibiting sympathetic output in CNS-intact anesthetized rats. On the other hand, noxious visceral stimulation results in an increase in sympathetic-induced MAP in spinalized anesthetized rats.

Anesthesia↗

Analgesic effect of electroacupuncture on complete Freund's adjuvant-induced inflammatory pain in mice: a model of antipain treatment by acupuncture in mice.

Electroacupuncture (EA) was applied bilaterally to the acupoints of Zu-san-li (ST-36) and Kun-lun (BL-60) in the hindlimbs of mice. The therapeutic effect of EA on inflammatory pain induced by an ipsilateral injection of complete Freund's adjuvant (CFA) into the right paw of the mouse was investigated in this study. The time of paw-withdrawal latency (PWL) was used as an indicator for judging the intensity of the pain induced by the CFA injection. The EA effects were divided into immediate (PWL tests within 2 h after EA treatment) and cumulative (PWL tests during and after repetitive EA treatments for 3 weeks) effects. As immediate effects, PWL was significantly shortened in the CFA-injected paw, but was again prolonged 20 min after an EA treatment and lasted until 30 min after. As cumulative effects, PWL was significantly shortened in the CFA-injected paw, but recovered from the 2nd to the 8th day during repetitive EA treatments. No such effects could be observed after sham EA treatment, which resulted in behavior similar to that in untreated animals. These results demonstrate that the CFA-induced inflammatory pain in mice is an ideal model system for the investigation of EA effects and may serve as a valuable reference for the clinical treatment of inflammatory pain in human beings. Furthermore, the mouse pain model opens the possibility to apply the investigation also to transgenic mice.

Acupuncture Points↗

Molecular epidemiology of Mycobacterium tuberculosis in China: a nationwide random survey in 2000.

OBJECTIVE: To determine the contribution of the Mycobacterium tuberculosis (TB) Beijing genotype to the population structure of M. tuberculosis complex in China. DESIGN: Genotypes of 441 mycobacterial isolates were determined by spoligotyping and IS6110 restriction fragment length polymorphism (RFLP). The isolates were from a nationwide random survey for the epidemiology of TB conducted in 2000, and the drug susceptibility patterns and epidemiological data were known. RESULT: A total of 408 samples contained M. tuberculosis as determined by spoligotyping. Of the M. tuberculosis strains, 64.9% (265/408) were of the Beijing genotype. Using the chi-squared test, no statistically significant differences were observed in the proportion of Beijing genotype TB in patients of different sex, age or living in different areas of the country, but a significant difference was observed with multidrug-resistant (MDR) TB: 77.8% (42/ 54) of MDR isolates were of the Beijing genotype vs. 60.2% (213/354) of the drug-susceptible isolates. In the multivariate logistic regression model, the Beijing genotype was significantly associated with region and not with MDR. CONCLUSION: The M. tuberculosis Beijing genotype has prevailed in China for at least five decades and is associated with region.

Adolescent↗

Electro-acupuncture relieves chronic visceral hyperalgesia in rats.

Acupuncture treatment is one of the most desirable choices for the management of pain including chronic visceral pain, but its scientific evidence and laws of action are not very clear at this point. In this study, we examined the immediate and cumulative effects of electro-acupuncture (EA) on chronic visceral pain induced by colorectal distention (CRD) stimuli in rats using an irritable bowel syndrome (IBS) model (a chronic visceral hypersensitivity model). The results demonstrated that EA could significantly depress both abnormally increased abdominal withdrawal reflex (AWR) scores and the magnitude of electromyograms (EMGs) recorded from the rectus abdominis in response to CRD stimulation at strengths of 20, 40, 60, and 80 mmHg. Repeated EA treatment for 14 days showed that the effects of EA on both abnormal AWRs and EMGs appeared 2-4 days after the start of the EA application session, gradually enhanced to its maximum within 8-12 days, and lasted 5 days after EA treatment stopped. These data provide evidence that visceral pain associated with the rat IBS model can be effectively treated by EA and opens up the possibility of clinical treatment of chronic visceral pain with acupuncture.

Animals↗

Risk assessment of exposure to volatile organic compounds in different indoor environments.

The lifetime cancer risks of exposure of cooks and food service workers, office workers, housewives, and schoolchildren in Hong Kong to volatile organic compounds (VOCs) in their respective indoor premises during normal indoor activities were assessed. The estimated cancer risk for housewives was the highest, and the second-highest lifetime cancer risk to VOC exposure was for the groups of food service and office workers. Within a certain group of the population, the lifetime cancer risk of the home living room was one to two orders of magnitude higher than that in other indoor environments. The estimated lifetime risks of food service workers were about two times that of office workers. Furthermore, the cancer risks of working in kitchen environments were approximately two times higher than the risks arising from studying in air-conditioned classrooms. The bus riders had higher average lifetime cancer risks than those travelling by Mass Transit Railway. For all target groups of people, the findings of this study show that the exposures to VOCs may lead to lifetime risks higher than 1 x 10(-6). Seven indoor environments were selected for the measurement of human exposure and the estimation of the corresponding lifetime cancer risks. The lifetime risks with 8-h average daily exposures to individual VOCs in individual environments were compared. People in a smoking home had the highest cancer risk, while students in an air-conditioned classroom had the lowest risk of cancer. Benzene accounted for about or more than 40% of the lifetime cancer risks for each category of indoor environment. Nonsmoking and smoking residences in Hong Kong had cancer risks associated with 8-h exposures of benzene above 1.8 x 10(-5) and 8.0 x 10(-5), respectively. The cancer risks associated with 1,1-dichloroethene, chloroform, methylene chloride, trichloroethene, and tetrachloroethene became more significant at selected homes and restaurants. Higher lifetime cancer risks due to exposure to styrene were only observed in the administrative and printing offices and air-conditioned classrooms. Higher lifetime cancer risks related to chloroform exposures were observed at the restaurant and the canteen.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

[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↗

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↗