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Biomedical subjects

Y Zhou

Publications and source records attributed to Y Zhou.

At least 55 records · Page 3Linked to original sources
PubMed2005

Evaluation of nebulizer performance under various humidity conditions.

Jet nebulizers are a drug delivery tool commonly used for treating respiratory diseases. When a nebulizer generates aerosols, the rate at which droplets evaporate depends on humidity conditions around the nebulizer outlet. Because the relative humidity (RH) of the air affects the evaporation rate, the aerosol distribution and drug delivery dose is also affected by RH. Four nebulizers were chosen for comparison in this study: PARI LC Plus (PARI Respiratory Equipment, Inc., Midlothian, VA), SideStream (Medic-Aid Ltd., UK), VixOne (Westmed, Inc., Tucson, AZ), and Micromist (Hudson Respiratory Care Inc., Temecula, CA). Two different formulations were used: albuterol (liquid solution) and budesonide (suspension). Particle distribution (mass median aerodynamic diameter [MMAD] and geometric standard deviation [GSD]), nebulizer efficiency (total efficiency and respirable fraction [RF] efficiency for particles less than 4.7 microm), and dead volume (the amount of solution remaining after nebulization) were compared at the RH of 5%, 50%, and 80%. Our results showed that the MMAD increased (p value varied from <0.001 to 0.016) with the increase in RH, except for with the VixOne unit with albuterol (p = 0.24). The MMAD from the budesonide always appeared higher than from the albuterol. The RF (and thus, the inhalation dose) was lower with a higher RH. Except for the PARI LC Plus with budesonide, the RF decreased approximately 15-27% when the RH rose from 5% to 50%. For the PARI LC Plus nebulizer, the lower dead volume (0.22 mL) with higher residual drugs (62.3% of total drug) was obtained at an RH of 5% comparing the RH of 50% and 80% because of the unit's unique design.

Aerosols↗
PubMed2005

Trait-associated sequence variation in the bovine growth hormone receptor 1A promoter does not affect promoter activity in vitro.

Growth hormone (GH) plays a central role in growth and metabolism in cattle by binding to growth hormone receptor (GHR) and stimulating production of insulin-like growth factor 1 (IGF1). Two sequence variations in the promoter transcribing a major GHR mRNA variant, GHR 1A mRNA, have been reported to be associated with quantitative differences in growth rate or blood concentration of IGF1 in cattle. One such variation is in the length of a TG-repeat, being 11 or 16-20; the other variation is in the nucleotide 155 bp upstream from the transcription start site, being G or A. In this study, we determined whether these sequence variations would affect the activity of GHR 1A promoter. We cloned GHR 1A promoters bearing different sequence variations and linked each of them to a reporter gene. Transient transfection analyses revealed that these promoter-reporter constructs did not differ in reporter gene expression. Cotransfection analyses demonstrated that they also did not differ in activation by hepatocyte nuclear factor 4alpha, hepatocyte nuclear factor 4gamma and nuclear receptor subfamily 2 group F member 2, known transcription factors for bovine GHR 1A promoter. These in vitro results, together with a previous observation that neither the nucleotide 155 bp upstream from the transcription start site nor the TG-repeat was part of the GHR 1A promoter region interacting with nuclear proteins from bovine liver, do not support a cause-effect relationship between the reported sequence variations and the associated changes in growth rate or blood IGF1 concentration in cattle.

Animals↗
PubMed2005

Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer.

BACKGROUND: The FAS and FASL system plays a key role in regulating apoptotic cell death and corruption of this signalling pathway has been shown to participate in immune escape and tumorigenesis. There is reduced expression of FAS but elevated expression of FASL in many types of human cancers including lung cancer. We recently reported an association between functional polymorphisms in FAS (-1377G-->A) and FASL (-844T-->C) and risk of oesophageal cancer. OBJECTIVE: To examine the contribution of these polymorphisms to risk of developing lung cancer. METHODS: Genotypes of 1000 lung cancer patients and 1270 controls were analysed by PCR based restriction fragment length polymorphism. Associations with risk of lung cancer were estimated by logistic regression. RESULTS: Compared with non-carriers, there was a 1.6 fold excess risk of developing lung cancer for carriers of the FAS -1377AA genotype (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.21 to 2.10; p = 0.001), and 1.8 fold excess risk (OR 1.79, 95% CI 1.26 to 2.52; p = 0.001) for carriers of FASL -844CC. Gene-gene interaction of FAS and FASL polymorphisms increased risk of lung cancer in a multiplicative manner (OR for the carriers of both FAS -1377AA and FASL -844CC genotypes 4.18, 95% CI 2.83 to 6.18). Gene-environment interaction of FAS or FASL polymorphism and smoking associated with increased risk of lung cancer was also found. CONCLUSION: These results are consistent with our initial findings in oesophageal cancer and further support the hypothesis that the FAS and FASL triggered apoptosis pathway plays an important role in human carcinogenesis.

Aged↗
PubMed2005

The NFkappaB pathway and endocrine-resistant breast cancer.

Endocrine therapy with an estrogen receptor (ER)-targeted antiestrogen, such as tamoxifen, or estrogen ablation by aromatase inhibitors is clinically indicated for the management of all forms of ER-positive breast cancer. However, 30-50% of ER-positive breast cancer cases fail to benefit clinically from endocrine therapy alone, and recent molecular evidence suggests that 'crosstalk' pathways originating from activated receptor tyrosine kinases and/or other proliferative and survival signals may be contributing to this endocrine resistance. Molecular identification and validation of candidate ER crosstalking pathways will likely lead to clinically important prognostic markers and targets for the application of novel therapeutics in combination with standard endocrine agents. This review focuses on a critical survival and proliferation pathway involving activation of nuclear factor-kappaB (NFkappaB), a family of ubiquitously expressed transcription factors that for nearly two decades have been known to be critical regulators of mammalian immune and inflammatory responses, and more recently have been associated with chemotherapy resistance. With the demonstration that activation of NFkappaB is absolutely required for normal mammary gland development, NFkappaB involvment in human breast cancers was initially explored and linked to the development of hormone-independent (ER-negative) breast cancer. Newer clinical evidence now implicates NFkappaB activation, particularly DNA-binding by the p50 subunit of NFkappaB, as a potential prognostic marker capable of identifying a high-risk subset of ER-positive, primary breast cancers destined for early relapse despite adjuvant endocrine therapy with tamoxifen. Furthermore, initial preclinical studies suggest that treatment strategies designed to prevent or interrupt activation of NFkappaB in cell-line models of these more aggressive, ER-positive breast cancers can restore their sensitivity to such standard endocrine agents as tamoxifen.

Antineoplastic Agents, Hormonal↗
PubMed2005

Activation of antitumor cytotoxic T lymphocytes by fusion of patient-derived dendritic cells with autologous osteosarcoma.

BACKGROUND AND AIM: Fusion of human dendritic cells (DCs) with tumor cells is an effective approach for delivering tumor antigens to DCs, and DC/tumor fusion cells are potent stimulators of autologous T cells. However, the integration and morphology of DC/osteosarcoma fusion cells has not been examined. This study was designed to investigate the antitumor effects of tumor vaccine produced by electrofusion between human osteosarcoma cells and DCs. METHODS: In the present study, we eletrofused patient-derived DCs to autologous osteosarcoma cells. The fusion cells possessed the properties of both patient cells. After electrofusion, the cytoplasm of the two cells was integrated, whereas their nuclei remained separate entities. The intracellular structure was observed on fusion cells under the transmission electron microscope. RESULTS: Coculture of patient-derived peripheral blood mononuclear cells (PBMC) with DC/tumor fusion cells resulted in activation of T cells as assessed by standard cytotoxic T lymphocytes (CTLs) assays. CONCLUSIONS: The present study provides valid evidence on integration of human DCs and tumor cells and links their properties to T cell activation. The fusion cells may thus represent a promising strategy for DC-based immunotherapy of patients with osteosarcoma.

Cancer Vaccines↗
PubMed2004

Human insulin and desamido human insulin isotherms in ethanol-water reversed phase systems.

The multi-component isotherms for human insulin (HI) and desamido human insulin (dHI) over reversed phase packing (C18) and with 29.8% (w/w) ethanol-water as mobile phase have been determined experimentally. The isotherms of HI in ethanol-water differ from those obtained with the more commonly applied methanol-water and acetonitrile-water mobile phase, as described in this paper. The isotherm exhibits anti Langmuirian behavior and can be very well modeled by an anti Langmuir isotherm presented in this paper. The HI and dHI anti Langmuir isotherm are determined as: qHI = (8.4C(HI) + 3C(HI)CdHI)/(1 - 0.05C(HI) - 0.14CdHI + 0.04C(HI)CdHI) and qdHI = (11.4CdHI + 2C(HI)CdHI)/ (1 - 0.05C(HI) - 0.14CdHI + 0.04C(HI)CdHI)

Chromatography, High Pressure Liquid↗
PubMed2004

Steinernema aciari sp. n. (Nematoda: Steinernematidae), a new entomopathogenic nematode from Guangdong, China.

A new species of entomopathogenic nematode, Steinernema aciari sp. n. was described. It was recovered from a soil sample collected from Haimen town, Shantou district in the eastern coast of Guangdong province, the People's Republic of China during a survey for entomopathogenic nematodes. S. aciari sp. n. belongs to the Steinernema glaseri group. It can be separated from all described Steinernema species by the combined morphological and morphometrical characters of various stages of the nematodes. For male, the new species can be recognized by spicule length (86+/-6.3 microm); spicule tip blunt with a hook-like structure; gubernaculum with a short and Y-shaped cuneus and corpus well-separated posteriorly. For infective juvenile, the combination of the following characters: body length (1113+/-68 microm), distance from anterior end to excretory pore (95+/-3.7 microm), tail length (78+/-5.2 microm), and E % (123+/-7) can be used to differentiate the new species from other nematodes. For female, the tail (conoid with a long mamillate terminus and a distinct postanal swelling) and vulva (slightly protruding from body surface with conspicuous double flapped epiptygma) shapes can be used as diagnostic characters for the new species. The new species can also be distinguished from other Steinernema species by DNA sequences of either a partial 28S rDNA or the internal transcribed spacer regions of rDNA, and from the close related species S. glaseri, Steinernema longicaudum CWL05, and Steinernema guangdongense by cross-breeding test.

Animals↗
PubMed2004

Additive effects of combined valsartan and spironolactone on cardiac aldosterone escape in spontaneously hypertensive rats.

The additive effects of combined valsartan and spironolactone on plasma and cardiac aldosterone escape were evaluated in spontaneously hypertensive rats (SHRs). Twenty-four SHRs were treated with valsartan (30 mg/kg body weight per day), spironolactone (20 mg/kg body weight per day) and a combination of both for 4 months. Blood was collected and plasma aldosterone (PA) was estimated with radioimmunoassay (RIA). Ex vivo heart perfusion was performed, the ex vivo cardiac aldosterone (EXCA) was assessed by RIA after high-performance liquid chromatography separation. PA and EXCA were significantly decreased after one month but increased after 4 months in valsartan administration group. The combined valsartan and spironolactone therapy normalized cardiac aldosterone levels. This study provides the first evidence that the long-term treatment with Angiotensin II type 1 receptor antagonist (AT1A) induces local aldosterone escape in cardiovascular tissue, whereas the combined AT1A and spironolactone therapy inhibits the escape in hypertensive rats.

Aldosterone↗
PubMed2004

The use of a new logistic regression model for predicting the outcome of pregnancies of unknown location.

BACKGROUND: The aim of this study was to generate and evaluate new logistic regression models from simple demographic and hormonal data to predict the outcome of pregnancies of unknown location (PULs). METHODS: Data were collected prospectively from 185 consecutive women classified as having a PUL by transvaginal scan; blood was taken at presentation and 48 h later to measure serum progesterone and HCG. These women were followed-up until the outcome was established: an intrauterine pregnancy (IUP), an ectopic pregnancy (EP) or a failing PUL. Three multi-categorical logistic regression models were tested. M1 was based on the HCG ratio (rate of change in HCG over 48 h), M2 was based on the average progesterone level (the mean of the progesterone level at 0 and 48 h) and M3 was based on the patient's age. RESULTS: A total of 102 failing PULs, 63 IUPs and 20 EPs were used in the training set to develop the new models. The best of these models, M3, gave a retrospective area under the receiver operating characteristic (ROC) curve of 0.984 for failing PUL, 0.995 for IUP and 0.920 for EP. All three models were tested prospectively on the test set of 196 cases. M1 outperformed M2 and M3 when tested prospectively. The area under the ROC curve (AUC) was 0.975 for failing PUL, 0.966 for IUP and 0.885 for EP. M1, for the detection of EP, had a sensitivity of 91.7%, a specificity of 84.2%, a positive likelihood ratio of 5.8, a positive predictive value of 27.5% and a negative predictive value of 99.4%. CONCLUSIONS: The logistic regression model M1, can predict which PULs will become failing PULs, IUPs and, most importantly, EPs based on the patient's HCG ratio alone.

Chorionic Gonadotropin↗
PubMed2004

Microdissection and molecular manipulation of single chromosomes in woody fruit trees with small chromosomes using pomelo (Citrus grandis) as a model. I. Construction of single chromosomal DNA libraries.

Construction of single chromosomal DNA libraries by means of chromosome microdissection and microcloning will be useful for genomic research, especially for those species that have not been extensively studied genetically. Application of the technology of microdissection and microcloning to woody fruit plants has not been reported hitherto, largely due to the generally small sizes of metaphase chromosomes and the difficulty of chromosome preparation. The present study was performed to establish a method for single chromosome microdissection and microcloning in woody fruit species using pomelo as a model. The standard karyotype of a pomelo cultivar ( Citrus grandis cv. Guanxi) was established based on 20 prometaphase photomicrographs. According to the standard karyotype, chromosome 1 was identified and isolated with fine glass microneedles controlled by a micromanipulator. DNA fragments ranging from 0.3 kb to 2 kb were acquired from the isolated single chromosome 1 via two rounds of PCR mediated by Sau3A linker adaptors and then cloned into T-easy vectors to generate a DNA library of chromosome 1. Approximately 30,000 recombinant clones were obtained. Evaluation based on 108 randomly selected clones showed that the sizes of the cloned inserts varied from 0.5 kb to 1.5 kb with an average of 860 bp. Our research suggests that microdissection and microcloning of single small chromosomes in woody plants is feasible.

Blotting, Southern↗
PubMed2004

An expression profile of human pancreatic islet mRNAs by Serial Analysis of Gene Expression (SAGE).

AIMS/HYPOTHESIS: The Human Genome Project seeks to identify all genes with the ultimate goal of evaluation of relative expression levels in physiology and in disease states. The purpose of the current study was the identification of the most abundant transcripts in human pancreatic islets and their relative expression levels using Serial Analysis of Gene Expression. METHODS: By cutting cDNAs into small uniform fragments (tags) and concatemerizing them into larger clones, the identity and relative abundance of genes can be estimated for a cDNA library. Approximately 49,000 SAGE tags were obtained from three human libraries: (i) ficoll gradient-purified islets (ii) islets further individually isolated by hand-picking, and (iii) pancreatic exocrine tissue. RESULTS: The relative abundance of each of the genes identified was approximated by the frequency of the tags. Gene ontology functions showed that all three libraries contained transcripts mostly encoding secreted factors. Comparison of the two islet libraries showed various degrees of contamination from the surrounding exocrine tissue (11 vs 25%). After removal of exocrine transcripts, the relative abundance of 2180 islet transcripts was determined. In addition to the most common genes (e.g. insulin, transthyretin, glucagon), a number of other abundant genes with ill-defined functions such as proSAAS or secretagogin, were also observed. CONCLUSION/INTERPRETATION: This information could serve as a resource for gene discovery, for comparison of transcript abundance between tissues, and for monitoring gene expression in the study of beta-cell dysfunction of diabetes. Since the chromosomal location of the identified genes is known, this SAGE expression data can be used in setting priorities for candidate genes that map to linkage peaks in families affected with diabetes.

Chromosomes, Human, Pair 1↗
PubMed2004

Probe selection algorithm for oligonucleotide array-based medium-resolution genotyping.

Medium-resolution genotyping has the goal of distinguishing different subgroups instead of each element in a group. An oligonucleotide array provides an inexpensive, high-throughput method to identify differences in DNA sequence among individuals, which is fundamental for genotyping. As the cost and difficulty of designing and fabricating the oligonucleotide array dramatically increase with the number of probes used, it is therefore important to have a design with a minimum number of probes meeting the requirement of medium-resolution genotyping. The first algorithm for designing and selecting probes for oligonucleotide array-based medium-resolution typing is reported. The goal in deriving the algorithm was to select a minimum number of probes from a large probe set on the premise of minimum loss of resolution. The algorithm, which was based on entropy, conditional entropy and mutual information theory, was used to select the minimum number of probes from a large probe set. The algorithm was tested on a human leukocyte antigen (HLA) sequence data set Thirty probes were selected from 390 probes for HLA-A, and 60 probes were selected from 767 probes for HLA-B. Although the number of probes was reduced by almost ten times, the distinguishability was reduced only a little, by 0.45% (from 99.90% to 99.45%) for HLA-A and 0.27% (from 99.84% to 99.57%) for HLA-B, respectively. This is a satisfactory and practical result.

Algorithms↗
PubMed2004

On the microstructure of biocomposites sintered from Ti, HA and bioactive glass.

Sintering reactions and fine structures of the biocomposites prepared from powder mixtures of titanium ( alpha -Ti), hydroxyapatite (HA) and bioactive glass (BG) (SiO2-CaO-P2O5-B2O3-MgO-TiO2-CaF2) were investigated by X-ray diffraction and transmission electron microscopy. The results showed that complex reactions among the starting materials mainly depended on the initial Ti/HA ratios as well as the sintering temperatures. And the reaction could be expressed by the following illustrative equation: Ti+Ca10(PO4)6(OH)2-->CaTiO3+CaO+TixPy+(Ti2O)+(Ca4P2O9)+H2O.

Biocompatible Materials↗
PubMed2004

Theoretical analysis of drug release into a finite medium from sphere ensembles with various size and concentration distributions.

Release kinetics for heterogeneous sphere ensembles with a dissolved drug, i.e., initial drug loading below or equal to the drug solubility in the matrix, in a finite external medium was modeled with consideration of heterogeneity among and within spheres. Numerical solutions were obtained using the finite element method for sphere ensemble with normal or log-normal distribution of particle size or initial drug loading among spheres. Exact series solutions were derived for ensembles with various initial loading distributions within spheres, namely linear, quadratic, sigmoidal and uniform distribution, using their mean or average radii. Simplified solutions retaining only one term of the series for non-uniform distributions and three terms for uniform distribution were suggested because of their good approximation to the exact solution. The results of finite element analysis showed that the release rate of an ensemble decreased with increasing standard deviation of particle size. Using weight-average radii in the exact solution gave a prediction of release profile closer to that from the actual size distribution than using mean radii. The three non-uniform loading patterns within spheres all showed reduced initial burst and release rate, leading to more steady release rates than uniform loading, among which the sigmoidal distribution offered the best near-zero order release. Non-uniform initial loading among spheres seemed to have insignificant influence on the release profiles. The volume ratio of liquid to a sphere ensemble played an important role in release kinetics. The derived analytical solutions are applicable to multiple spheres or a single sphere in a finite medium or in a perfect sink.

Algorithms↗
PubMed2004

Proteasomal inhibition induced by manganese ethylene-bis-dithiocarbamate: relevance to Parkinson's disease.

Maneb, a widely used fungicide, has been associated with Parkinsonism in humans. In experimental models, maneb and its major active element, manganese ethylene-bis-dithiocarbamate (Mn-EBDC) cause selective nigrostriatal neurodegeneration in mice and in rats, respectively. To investigate the mechanisms underlying this neurodegeneration, we studied the effects of Mn-EBDC on proteasomal function, which is decreased in patients with Parkinson's disease (PD), in a dopaminergic neuronal cell line (MES 23.5 or MES). The results demonstrated that exposure of MES cells to 6 microM Mn-EBDC for 7 days produced not only significant neurotoxicity but also inhibition of proteasomal chymotrypsin-like and postglutamyl peptidase activities. Proteasomal dysfunction was accompanied by formation of cytoplasmic inclusions that were positive for alpha-synuclein immunostaining and significantly increased sodium dodecyl sulfate-insoluble alpha-synuclein aggregation seen by Western blot analysis. In addition, there was a significant increase in oxidative stress, evidenced by elevated total protein carbonyl content, in cells treated with Mn-EBDC. Manipulation of intracellular reduced glutathione levels with N-acetyl-L-cysteine or L-buthionine sulfoximine pretreatment to modulate Mn-EBDC-mediated oxidative stress altered Mn-EBDC-mediated neurotoxicity, proteasomal dysfunction, and alpha-synuclein aggregation in these cells. These data suggest that neurotoxicity-induced by Mn-EBDC is at least partially attributable to Mn-EBDC-mediated proteasomal inhibition, and that the proteasome may be an important target by which environmental exposure modifies the risk for developing PD in vulnerable populations.

Amino Acid Sequence↗
PubMed2004

EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of nuclear factor-kappa B.

Erythroid differentiation-associated gene (EDAG) is considered to be a human hematopoiesis-specific gene. Here, we reported that downregulation of EDAG protein in K562 cells resulted in inhibition of growth and colony formation, and enhancement of sensitivity to erythroid differentiation induced by hemin. Overexpression of EDAG in HL-60 cells significantly blocked the expression of the monocyte/macrophage differentiation marker CD11b after pentahydroxytiglia myristate acetate induction. Moreover, overexpression of EDAG in pro-B Ba/F3 cells prolonged survival and increased the expression of c-Myc, Bcl-2 and Bcl-xL in the absence of interleukin-3 (IL-3). Furthermore, we showed that EDAG enhanced the transcriptional activity of nuclear factor-kappa B (NF-kappa B), and high DNA-binding activity of NF-kappa B was sustained in Ba/F3 EDAG cells after IL-3 was withdrawn. Inhibition of NF-kappa B activity resulted in promoting Ba/F3 EDAG cells death. These results suggest that EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of NF-kappa B.

Apoptosis↗
PubMed2004

Efficient bone formation by gene transfer of human LIM mineralization protein-3.

LIM mineralization protein (LMP) is a novel positive regulator of the osteoblast differentiation program. In humans, three different LMP splice variants have been identified: LMP-1, LMP-2, and LMP-3. Gene transfer of human LMP-1 (hLMP-1) induces expression of genes involved in bone formation, including certain bone morphogenetic proteins (BMPs), promotes bone nodule formation in vitro, ectopic bone formation in vivo, and is therapeutic in animal models of posterior thoracic and lumbar spine fusion. To examine the osteoinductive properties of the LMP-3 in vitro and in vivo, we have generated plasmid and adenoviral vectors expressing codon-optimized hLMP-3. Here we demonstrate that gene transfer of hLMP-3 induces expression of the bone-specific genes osteocalcin, osteopontin, and bone sialoprotein and induced bone mineralization in preosteoblastic and fibroblastic cells. We also demonstrate that hLMP-3 is able to induce bone mineralization and the expression of the bone-specific genes, BMP-2, OSX, RunX2, and alkaline phosphatase in human mesenchymal stem cells in a dose-dependent manner. Finally, we demonstrate that direct gene transfer of hLMP-3 into murine skeletal muscle results in ectopic bone formation more efficiently than BMP-2. These results demonstrate that hLMP-3 gene transfer can be used to promote bone formation in cell culture and in vivo as or more efficiently than BMP-2, thus establishing feasibility and efficacy of direct gene delivery of hLMP-3 to produce bone in vivo. These results suggest that gene transfer of hLMP-3 could be developed as a bone-inductive therapeutic agent for clinical applications.

3T3 Cells↗