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Biomedical subjects

Y Li

Publications and source records attributed to Y Li.

At least 181 records · Page 10Linked to original sources
PubMed2005

Effects of platelet binding on whole blood flow cytometry assays of monocyte and neutrophil procoagulant activity.

BACKGROUND: Monocytes and neutrophils form heterotypic aggregates with platelets initially via engagement of platelet surface P-selectin with leukocyte surface P-selectin glycoprotein ligand-1 (PSGL-1). The resultant intracellular signaling causes the leukocyte surface expression of tissue factor and activation of leukocyte surface Mac-1 (integrin alphaMbeta2, CD11b/CD18). The activation-dependent conformational change in monocyte surface Mac-1 results in the binding of coagulation factor Xa (FXa) and/or fibrinogen to Mac-1. The aim of this study was to develop whole blood flow cytometry assays of these procoagulant activities and to investigate the effects of platelet binding to monocytes and neutrophils. METHODS: Citrate or D-Phe-Pro-Arg-chloromethylketone (PPACK) anticoagulated whole blood was incubated with monoclonal antibodies against CD14 (PECy5), CD42a (PE), FITC-conjugated test antibody and an agonist, and then fixed with FACS lyse. Appropriate isotype negative controls were prepared in parallel. A BD FACSCalibur was used to analyze monocytes and neutrophils, which were identified based on CD14 fluorescence, forward and 90 degrees light scatter. These populations were further gated into CD42a-positive (platelet-bound) and CD42a-negative (platelet-free). Geometric mean fluorescence and per cent positive data were collected for each subpopulation to measure the binding of test antibodies directed at CD42a, tissue factor, coagulation FXa, bound fibrinogen, activated Mac-1, and CD11b. Compensation controls were prepared on six normal donors prior to the study and these settings were used throughout the 10 donor study. Negative controls verified the lack of cross talk, particularly in the quantified FITC and PE parameters. RESULTS: The physiologic agonists collagen and ADP increased monocyte-platelet and neutrophil-platelet aggregates and increased leukocyte surface Mac-1/CD11b and surface-bound tissue factor, FXa and fibrinogen. Whereas the increases in Mac-1/CD11b were mainly independent of leukocyte-platelet binding, the increases in surface-bound tissue factor, FXa and fibrinogen were mainly dependent on leukocyte-platelet binding. CONCLUSIONS: (i) We have developed novel whole blood flow cytometry assays to measure bound tissue factor, coagulation FXa, fibrinogen, activated Mac-1 and CD11b on the surface of monocytes and neutrophils, allowing independent analysis of monocytes and neutrophils with and without surface-adherent platelets. (ii) The monocyte and neutrophil surface binding of tissue factor, FXa and fibrinogen is mainly dependent on platelet adherence to monocytes and neutrophils, whereas the monocyte and neutrophil surface expression of CD11b and activated Mac-1 is mainly independent of platelet adherence to monocytes and neutrophils.

Adenosine Diphosphate↗
PubMed2005

Role of air distribution in SARS transmission during the largest nosocomial outbreak in Hong Kong.

UNLABELLED: Severe acute respiratory syndrome (SARS) is primarily transmitted by bio-aerosol droplets or direct personal contacts. This paper presents a detailed study of environmental evidence of possible airborne transmission in a hospital ward during the largest nosocomial SARS outbreak in Hong Kong in March 2003. Retrospective on-site inspections and measurements of the ventilation design and air distribution system were carried out on July 17, 2003. Limited on-site measurements of bio-aerosol dispersion were also carried out on July 22. Computational fluid dynamics simulations were performed to analyze the bio-aerosol dispersion in the hospital ward. We attempted to predict the air distribution during the time of measurement in July 2003 and the time of exposure in March 2003. The predicted bio-aerosol concentration distribution in the ward seemed to agree fairly well with the spatial infection pattern of SARS cases. Possible improvement to air distribution in the hospital ward was also considered. PRACTICAL IMPLICATIONS: Our study revealed the need for the development of improved ventilation and air-conditioning systems in an isolation ward or a general hospital ward for infectious respiratory diseases. The outbreak in Ward 8A, which was in a general hospital and could house nearly 40 patients, demonstrated the cross-infection risks of respiratory infectious diseases in hospitals if a potential highly infectious patient was not identified and isolated. Our example simulation, which extended the SARS Busters' design for an isolation room to Ward 8A, demonstrated that there was room for improvement to minimize cross-infection in large general hospital wards.

Aerosols↗
PubMed2005

Multi-zone modeling of probable SARS virus transmission by airflow between flats in Block E, Amoy Gardens.

UNLABELLED: More than 300 residents of a private high-rise housing estate were infected with severe acute respiratory syndrome within a short period during the 2003 epidemic in Hong Kong. The outbreak occurred after the identified index patient visited a flat on a middle floor in Block E of the Amoy Gardens estate on two nights. Approximately 45% of the subsequently infected people resided in Block E, while the other 55% of infected cases mainly resided in six other blocks close to Block E. The distribution of the infected flats in Block E conformed to a non-uniform spatial pattern. Probable environmental causes for airborne transmission associated with the air movements between flats in Block E are identified. The well-established multi-zone airflow modeling method was used to analyze the virus-laden bio-aerosol dispersion between flats through door and window leakage areas in Block E under six different scenarios. The distribution of infection risk in Block E matched with the virus concentrations in flats predicted with the use of multi-zone modeling. Our study shows the importance of ventilation design in high-rise residential apartments. PRACTICAL IMPLICATIONS: The present study on the Amoy Gardens outbreak presented a scenario in which crowded living spaces might lead to infection disasters. There is a need to improve the current sanitary drainage design and maintenance standards to avoid any leakage of foul gas into the indoor environments. Our study revealed the need for a review of indoor air quality and ventilation design in buildings including offices, homes and hotels. The study has implications to public health in, for example, the control of other airborne respiratory infectious diseases such as influenza, and in bio-terror safety in buildings.

Air Movements↗
PubMed2005

In vitro activities of novel 2-fluoro-naphthyridine-containing ketolides.

In vitro activities of erythromycin A, telithromycin, and two investigational ketolides, JNJ-17155437 and JNJ-17155528, were evaluated against clinical bacterial strains, including selected common respiratory tract pathogens. Against 46 macrolide-susceptible and -resistant Streptococcus pneumoniae strains, the MIC(90) (MIC at which 90% of the isolates tested were inhibited) of the investigational ketolides was 0.25 microg/ml, twofold lower than that of telithromycin and at least 64-fold lower than that of erythromycin A. Against erm(B)-containing pneumococci, the MIC(90) of all the ketolides was 0.06 microg/ml. The MIC(90) of the investigational ketolides against mef(A)-containing pneumococci or pneumococci with both mef(A) and erm(B) was 0.25 microg/ml, two-and fourfold lower, respectively, than that of telithromycin. In contrast, the MICs of the investigational ketolides against macrolide-resistant S. pneumoniae strains with ribosomal mutations were similar to or, in some cases, as much as eightfold higher than those of telithromycin. Against Haemophilus influenzae, MICs of all the ketolides were < or =2 microg/ml. Against three Moraxella catarrhalis isolates, the MIC of the ketolides was 0.25 microg/ml. The ketolides inhibited in vitro protein synthesis, with 50% inhibitory concentrations ranging from 0.23 to 0.27 microM. In time-kill studies against macrolide-susceptible and erm- or mef-containing pneumococci, the ketolides were bacteriostatic to slowly bactericidal, with 24-h log(10) decreases ranging from 2.0 to 4.1 CFU. Intervals of postantibiotic effects for the ketolides against macrolide-susceptible and -resistant S. pneumoniae were 3.0 to 8.1 h.

Anti-Bacterial Agents↗
PubMed2005

Visual acuity in northern China in an urban and rural population: the Beijing Eye Study.

AIM: To evaluate prevalence and demographic associations of visual impairment in an urban and rural population in northern China. METHODS: In the Beijing Eye Study, a population based cohort study in northern China, visual acuity was assessed for 8876 eyes (4438 subjects) according to a response rate of 83.4%. The study was divided into a rural part (1972 subjects) and an urban part (n=2466). Mean age was 56.20 (SD 10.59) years (median 56 years; range 40-101 years). RESULTS: Mean uncorrected visual acuity measured 0.72 (0.32) (median, 0.80), and mean best corrected visual acuity measured 0.91 (0.21) (median, 1.0). In a multiple regression analysis, best corrected visual acuity was significantly correlated with age (p<0.001), degree of nuclear cataract (p<0.001), amount of cortical cataract (p=0.014), amount of subcapsular cataract (p<0.001), educational background (p<0.001), and refractive error (p<0.001). Rural region versus urban region (p=0.34) and sex (p=0.053) were not statistically significantly associated with best corrected visual acuity. CONCLUSIONS: In northern China, determinants of a low degree of best corrected visual acuity are age, cataract, low educational background, and myopia. Despite marked differences in educational background and family income, sex, and rural area versus urban area are not markedly associated with best corrected visual acuity.

Adult↗
PubMed2005

Identification of discrete chromosomal deletion by binary recursive partitioning of microarray differential expression data.

DNA copy number abnormalities (CNA) are characteristic of tumours, and are also found in association with congenital anomalies and mental retardation. The ultimate impact of copy number abnormalities is manifested by the altered expression of the encoded genes. We previously developed a statistical method for the detection of simple chromosomal amplification using microarray expression data. In this study, we significantly advanced those analytical techniques to allow detection of localised chromosomal deletions based on differential gene expression data. Using three cell lines with known chromosomal deletions as model system, mRNA expression in those cells was compared with that observed in diploid cell lines of matched tissue origin. Results show that genes from deleted chromosomal regions are substantially over-represented (p<0.000001 by chi2) among genes identified as underexpressed in deletion cell lines relative to normal matching cells. Using a likelihood based statistical model, we were able to identify the breakpoint of the chromosomal deletion and match with the karyotype data in each cell line. In one such cell line, our analyses refined a previously identified 10p chromosomal deletion region. The deletion region was mapped to between 10p14 and 10p12, which was further confirmed by subtelomeric fluorescence in situ hybridisation. These data show that microarray differential expression data can be used to detect and map the boundaries of submicroscopic chromosomal deletions.

Cell Line↗
PubMed2005

Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans.

BACKGROUND: Congenital or childhood cataract is clinically and genetically a highly heterogeneous lens disorder in children. Autosomal dominant inheritance is most common. OBJECTIVE: To report the identification of a mutation in the human CRYGS gene. SUBJECTS AND METHODS: A large six generation family affected by progressive polymorphic cortical cataract was investigated. After excluding loci for known cataract candidate genes using 39 fluorescent microsatellite markers, a whole genome scan was carried out. RESULTS: The disease was associated with inheritance of a 20.7 cM locus on chromosome 3q26.3-qter, with a maximum LOD score of 6.34 (theta = 0) at marker D3S1602. Haplotype analysis indicated that the disease gene lay at approximately 2.8 Mb physical intervals between D3S1571 and D3S3570 and contained CRYGS on 3q27.3. By sequencing the CRYGS gene, a distinct 1619G-->T (AC068631) heterozygous missense mutation in exon 2 was identified, co-segregating with the disease phenotype in this family and resulting in a glycine (GGC) to valine residue (GTC) substitution in codon 18 (NP_060011). CONCLUSIONS: This report is the first description of a mutation in CRYGS with autosomal dominant cataract in humans.

Amino Acid Sequence↗
PubMed2005

Survey of oral microbial diversity using PCR-based denaturing gradient gel electrophoresis.

Polymicrobial biofilms in the human oral cavity exhibit marked diversity. PCR-based denaturing gradient gel electrophoresis (PCR-DGGE) surveys microbial diversity by displaying PCR-generated 16S rDNA fragments that migrate at different distances, reflecting the differences in the base-pair (i.e., % G+C) composition of the fragment. This study examined DGGE-generated diversity profiles of cultivable bacteria from individuals with different caries status. Initially, we developed a set of PCR-DGGE running conditions appropriate to oral bacteria. Next, we assessed migration standards from known oral bacterial reference strains. To test the methods, we profiled 20 bacterial saliva samples cultivated from young adults. The study produced a battery of species-specific 16S rDNA amplicons that could be used as a migration distance standard necessary for computer-assisted profile analysis. From the clinical samples, we found a significantly greater diversity of oral microbes in caries-free individuals compared with caries-active individuals (P = 0.01). These findings suggest thtat a portion of oral microbiota of caries-active individuals may be absent, suppressed, or replaced.

Actinomyces↗
PubMed2005

Mode of delivery and other maternal factors influence the acquisition of Streptococcus mutans in infants.

S. mutans plays a key role in dental caries. The extent to which perinatal events influence the acquisition of S. mutans is unclear. We hypothesized that several maternal factors, including the mode of delivery, influence the initial acquisition of S. mutans in infants. A prospective cohort study was conducted in 156 mother-infant pairs. The study found that maternal gestational age (p = 0.04), S. mutans level (p = 0.02), caries score (p = 0.02), sexually transmitted disease (STD) infection experience (p = 0.01), and family income (p = 0.03) had significant effects on the acquisition of S. mutans. Among infants who became infected, those delivered by Caesarean section acquired S. mutans 11.7 mos earlier than did vaginally delivered infants (p = 0.038). C-section infants harbored a single genotype of S. mutans that was identical to that of their mothers (100% fidelity). Analysis of the data demonstrated the possible perinatal influences on infants' acquisition of a member of the cariogenic microbiota, and its potential effect on caries outcome.

Analysis of Variance↗
PubMed2005

The Oral Fluid MEMS/NEMS Chip (OFMNC): diagnostic and translational applications.

The ability to monitor health status, disease onset and progression, and treatment outcome through non-invasive means is a most desirable goal in health-care promotion and delivery. There are three prerequisites for this goal to be realized: specific biomarkers associated with a health or disease state, a non-invasive approach to detect and monitor the biomarkers, and the technologies to discriminate between and among the biomarkers. We present a roadmap to achieve these goals using oral fluids as the diagnostic medium to scrutinize the health and/or disease status of individuals. This is an ideal opportunity to bridge state-of-the-art micro-/nano-electromechanical system (MEMS/NEMS) sensors to oral fluid for diagnostic applications. As the "mirror of body", oral fluid is a perfect medium to be explored for health and disease surveillance. The translational applications and opportunities are enormous.

Biomarkers↗
PubMed2005

Detection of vvIBDV in vaccinated SPF chickens.

The purpose of our experiment was to investigate, if apparently healthy, vaccinated chickens may be involved in maintaining and spreading infectious bursal disease virus (IBDV) in poultry environments. We aimed at simultaneous detection and identification of very virulent field strain IBDV (vvIBDV) as well as vaccine strain IBDV in experimentally infected chickens. Two groups of specific pathogen free (SPF) chickens were vaccinated using the intermediate infectious bursal disease (IBD) vaccine D78. Group 1 was vaccinated at the age of one week and group 2 at the age of three weeks. Both groups were challenged with vvl BDV at the age of four weeks. A third, vaccinated, non-challenged group served as negative control. No clinical symptoms were observed in any of these groups. The chickens were euthanised and submitted to autopsy and sample preparation in groups of three at fixed intervals from the age of 28 to 44 days. Gross pathological lesions were not observed. Lymphoid tissues from the bursa of Fabricius, bone marrow, spleen and thymus in addition to cloacal- and bursal swaps were analysed by one-step reverse transcription polymerase chain reaction (RT-PCR). Positive results were confirmed by two-step strain specific duplex (DPX) RT-PCR. The vaccine strain was detected in bursa tissues from all groups, while the challenge strain was detected in few bursal as well as non-bursal tissue samples. The results indicate a possibility of replication of vvlBDV in vaccinated chickens.

Animals↗
PubMed2005

The use of relaxin improves healing in injured muscle.

To improve the functional recovery of injured skeletal muscle, we have focused our efforts on both enhancement of muscle regeneration and prevention of fibrosis. The polypeptide cytokine/growth factor relaxin can inhibit fibrous tissue formation in many tissues. As a member of the insulin-like growth factor family, relaxin also is a potential stimulator of muscle regeneration. In the current experiment, we examined the antifibrotic effect of relaxin in injured skeletal muscle. We also investigated if the injection of relaxin would influence muscle regeneration after injury. Our results demonstrate that relaxin treatment improved histologic and physiologic healing of muscles subjected to traumatic injury.

Animals↗
PubMed2005

Effect of small-sized liposomal Adriamycin administered by various routes on a metastatic breast cancer model.

The antitumor effects of small-sized liposomal Adriamycin (LADR) administered by various routes were investigated in rabbits bearing well-developed VX2 tumors in the mammary gland. Rabbits received s.c. or i.v., or s.c. combined with i.v., injections of LADR 6 weeks after tumor implantation. The i.v. route showed a significant inhibitory effect on breast tumors and distant metastases. In comparison, metastases in axillary and mediastinal lymph nodes were more efficiently inhibited after s.c. injection. LADR administered concurrently by both the i.v. and s.c. routes produced satisfactory therapeutic activities on both primary breast tumors and metastases in local-regional lymph nodes, lungs and liver, as shown by slowed growth rates, decreased mRNA expression of proliferating cell nuclear antigen, and extensive necrosis and apoptosis of tumor cells. It is concluded that small-sized LADR administered s.c. provides reliable efficacy on lymphatic metastases of breast cancer and that the addition of treatment by the s.c. route to that by the conventional i.v. route can be recommended as a promising procedure to enhance chemotherapeutic effects in patients with metastatic breast cancer.

Animals↗
PubMed2005

A survey of selected heavy metal concentrations in Wisconsin dairy feeds.

Heavy metals such as zinc (Zn), copper (Cu), chromium (Cr), arsenic (As), cadmium (Cd), and lead (Pb) are potential bioaccumulative toxins of the dairy production system. The heavy metal content of dairy feeds, however, remains poorly documented, particularly in the United States. This survey determined the heavy metal content of 203 typical dairy ration components sampled from 54 dairy farms in Wisconsin. Lowest heavy metal concentrations were found in homegrown alfalfa (Medicago sativa L.) hay and haylage, and corn (Zea mays L.) grain and silage. Highest metal concentrations were found in purchased feeds, particularly mineral supplements, and to a lesser extent corn- or soybean-based concentrates. Zinc and Cu were found at the highest concentration in complete dairy (total mixed and aggregated component) rations and reflected the deliberate addition of these metals to meet animal nutrient requirements although more than half the farms fed Cu and Zn above US recommended levels. Concentrations of Cr, As, Cd, and Pb were present in much lower concentrations and decreased in the order Cr > As > Pb > Cd. No complete Wisconsin dairy ration contained heavy metal concentrations above US maximum acceptable concentrations and would be unlikely to induce any toxic effects in dairy cattle. Concentrations of Cd in complete dairy rations were closest to US maximum acceptable concentrations, suggesting the greatest potential long-term risk to exceed US maximum acceptable concentrations if whole farm levels of Cd were to increase in the future. With the exception of Pb, the main sources of Zn, Cu, Cr, As, and Cd in the complete dairy feed ration originated from imported feed. The continued importation of heavy metals in dairy feed is likely to be associated with accumulation of these metals in soils where manure is applied. Although the cycling of many heavy metals through the dairy food chain will be limited by factors such as a soil's cation exchange capacity, pH, salinity, and phytotoxicity of the metal, these may be less limiting for Cd. It is important that sources of Cd in the dairy system are identified and minimized to prevent problems associated with Cd accumulation in the dairy soil system arising over the long-term.

Animal Feed↗
PubMed2004

Human hepatitis B virus X protein promotes cell proliferation and inhibits cell apoptosis through interacting with a serine protease Hepsin.

The X protein of human hepatitis B virus (HBV) acts as an indirect transcriptional transactivator to regulate the expression of many viral and cellular genes as well as playing a critical role in the development of hepatocellular carcinoma. While the biological importance of HBx has been well established, the cellular and molecular bases of its function remain largely undefined. In this study, we isolated a new HBV field strain from a patient with chronic viral infection. The X protein encoded by this virus was used as a bait protein for screening a human liver cDNA library using a yeast two-hybrid system. Several cell proteins were identified as new HBx interacting partners, including a transmembrane serine protease, Hepsin. Direct interaction between HBx and Hepsin proteins was confirmed by in vitro and in vivo co-immunoprecipitation assays. HBx also co-localized with Hepsin in human cells as determined by confocal immunofluorescence microscopy. The interaction between HBx and Hepsin protein appeared to play a role in both promoting cell proliferation and blocking apoptosis in human liver tumor cell and normal liver cell lines. In addition, the complex of HBx and Hepsin promoted the expression of HBeAg in Hep G2.2.1.5 cells indicating that the association of these two proteins stimulated viral replication.

Apoptosis↗
PubMed2004

Sex steroid hormone metabolism and prostate cancer.

The growth and function of the prostate is dependent on androgens. The two predominant androgens are testosterone, which is formed in the testis from androstenedione and 5alpha-dihydrotestosterone, which is formed from testosterone by 5alpha-reductases and is the most active androgen in the prostate. Prostate cancer is one of the most common cancers among men and androgens are involved in controlling the growth of androgen-sensitive malignant prostatic cells. The endocrine therapy used to treat prostate cancer aims to eliminate androgenic activity from the prostatic tissue. Most prostate cancers are initially responsive to androgen withdrawal but become later refractory to the therapy and begin to grow androgen-independently. Using LNCaP prostate cancer cell line we have developed a cell model to study the progression of prostate cancer. In the model androgen-sensitive LNCaP cells are transformed in culture conditions into more aggressive, androgen-independent cells. The model was used to study androgen and estrogen metabolism during the transformation process. Our results indicate that substantial changes in androgen and estrogen metabolism occur in the cells during the process. A remarkable decrease in the oxidative 17beta-hydroxysteroid dehydrogenase activity was seen whereas the reductive activity seemed to increase. The changes suggest that during transformation estrogen influence is increasing in the cells. This is supported by the cDNA microarray screening results which showed over-expression of several genes up-regulated by estrogens in the LNCaP cells line representing progressive prostate cancer. Since local steroid metabolism controls the bioavailability of active steroid hormones in the prostate, the variations in steroid-metabolizing enzymes during cancer progression may be crucial in the regulation of the growth and function of the organ.

17-Hydroxysteroid Dehydrogenases↗
PubMed2004

Stability and instability of regulation of intracellular calcium.

[Ca2+]i is used as a signal in many tissues. In this review we discuss the mechanisms that regulate [Ca2+]i and, importantly, what determines their stability. Brief mention is made of the effects of feedback gain and delays on stability. The control of cytoplasmic Ca concentration is shown to be generally stable as Ca pumping is essentially an instantaneous function of [Ca2+]i. In contrast, regulation of the Ca content of intracellular stores may be less stable. One example of this is instability in the control of sarcoplasmic reticulum (SR) Ca content in cardiac muscle. An increase of SR Ca content increases the systolic Ca transient amplitude. This in turn decreases Ca influx into the cell and increases efflux, thereby restoring SR Ca to control levels. This feedback system has an inherent delay and is potentially unstable if the gain is increased beyond a certain level. This instability produces Ca transients of alternating amplitude and may contribute to the clinical syndrome of pulsus alternans.

Adaptation, Physiological↗