Biomedical subjects

H Zhang

Publications and source records attributed to H Zhang.

At least 343 records · Page 19Linked to original sources

PubMed2001

A rapid method for detecting conformational changes during differentiation and apoptosis of HL60 cells by Fourier-transform infrared spectroscopy.

The conformational changes of HL60 cells during differentiation and apoptosis are still not clearly understood. This study uses a new method, Fourier-transform infrared (FT-IR) spectroscopy, to analyse the changes of HL60 cells. We detected several differences among normal HL60 cells, differentiated cells induced by all-trans retinoic acid (ATRA) and PMA, and apoptotic cells induced by vincristine (VCR). The results suggest that the alpha-helix content of the membrane protein of differentiated HL60 cells induced by ATRA and PMA increased,and that the beta-sheet content of membrane proteins of apoptotic cells induced by VCR also increased. Also, C-O(H)-stretching modes of serine, threonine and tyrosine residues of cell proteins were shown to be distinctly different, but no significant differences were detected between cells differentiated along different lineages by ATRA and PMA.

Antineoplastic Agents↗

PubMed2001

PSA-NCAM modulates BDNF-dependent survival and differentiation of cortical neurons.

We show that the loss or inactivation of the polysialic acid (PSA) tail of neural cell adhesion molecule (NCAM) on rat cortical neurons in culture leads to reduced differentiation and survival. The mechanism by which this negative effect is mediated appears to involve the neuronal response to brain-derived neurotrophic factor (BDNF): (i) in the absence of PSA or in the presence of excess free PSA added to the culture medium, BDNF-induced cell signalling is reduced; (ii) the addition of exogenous BDNF to the medium reverses the effect of PSA loss or inactivation. These data suggest that PSA-NCAM, previously shown to modulate cell migration and plasticity, is needed for an adequate sensitivity of neurons to BDNF.

Animals↗

PubMed2001

ABA plays a central role in mediating the regulatory effects of nitrate on root branching in Arabidopsis.

The formation of lateral roots (LR) is a major post-embryonic developmental event in plants. In Arabidopsis thaliana, LR development is inhibited by high concentrations of NO3(-). Here we present strong evidence that ABA plays an important role in mediating the effects of NO3(-) on LR formation. Firstly, the inhibitory effect of NO3(-) is significantly reduced in three ABA insensitive mutants, abi4-1, abi4-2 and abi5-1, but not in abi1-1, abi2-1 and abi3-1. Secondly, inhibition by NO3(-) is significantly reduced, but not completely abolished, in four ABA synthesis mutants, aba1-1, aba2-3, aba2-4 and aba3-2. These results indicate that there are two regulatory pathways mediating the inhibitory effects of NO3(-) in A. thaliana roots. One pathway is ABA-dependent and involves ABI4 and ABI5, whereas the second pathway is ABA-independent. In addition, ABA also plays a role in mediating the stimulation of LR elongation by local NO3(-) applications.

Abscisic Acid↗

PubMed2001

Dopaminergic cell death induced by MPP(+), oxidant and specific neurotoxicants shares the common molecular mechanism.

Recent etiological study in twins (Tanner et al. 1999) strongly suggests that environmental factors play an important role in typical, non-familial Parkinson's disease (PD), beginning after age 50. Epidemiological risk factor analyses of typical PD cases have identified several neurotoxicants, including MPP(+) (the active metabolite of MPTP), paraquat, dieldrin, manganese and salsolinol. Here, we tested the hypothesis that these neurotoxic agents might induce cell death in our nigral dopaminergic cell line, SN4741 (Son et al. 1999) through a common molecular mechanism. Our initial experiments revealed that treatment with both MPP(+) and the other PD-related neurotoxicants induced apoptotic cell death in SN4741 cells, following initial increases of H(2)O(2)-related ROS activity and subsequent activation of JNK1/2 MAP kinases. Moreover, we have demonstrated that during dopaminergic cell death cascades, MPP(+), the neurotoxicants and an oxidant, H(2)O(2) equally induce the ROS-dependent events. Remarkably, the oxidant treatment alone induced similar sequential molecular events: ROS increase, activation of JNK MAP kinases, activation of the PITSLRE kinase, p110, by both Caspase-1 and Caspase-3-like activities and apoptotic cell death. Pharmacological intervention using the combination of the antioxidant Trolox and a pan-caspase inhibitor Boc-(Asp)-fmk (BAF) exerted significant neuroprotection against ROS-induced dopaminergic cell death. Finally, the high throughput cDNA microarray screening using the current model identified downstream response genes, such as heme oxygenase-1, a constituent of Lewy bodies, that can be the useful biomarkers to monitor the pathological conditions of dopaminergic neurons under neurotoxic insult.

1-Methyl-4-phenylpyridinium↗

PubMed2001

PTCH mutations in squamous cell carcinoma of the skin.

Ultraviolet light exposure is the major risk factor for the development of squamous cell carcinoma in Caucasians. Mutations in the tumor suppressor gene p53 have been identified in both squamous cell carcinomas and basal cell carcinomas. The human homolog of the Drosophila patched gene, has been shown to be mutated in sporadic basal cell carcinomas; however, mutations in the patched gene have not been found in squamous cell carcinoma. In this study, we screened a total of 20 squamous cell carcinoma samples for mutations in the patched gene. Using polymerase chain reaction-single strand conformation polymorphism as an initial screening method, we identified one non-sense mutation, two mis-sense mutations and three silent mutations in five squamous cell carcinoma samples. In one squamous cell carcinoma sample, we identified a tandem GG-->AA transitional change at nucleotide 3152 in exon 18 of the patched gene that resulted in a premature stop codon at codon 1051. The three squamous cell carcinoma samples containing non-sense and mis-sense mutations were isolated from individuals with histories of multiple basal cell carcinoma. Sequence analysis of the p53 gene in these five squamous cell carcinoma samples identified one CC-->TT and three C-->T ultraviolet-specific nucleotide changes. Our study provides evidence that the patched gene is mutated in squamous cell carcinoma from individuals with a history of multiple basal cell carcinoma. The identification of ultraviolet-specific nucleotide changes in both tumor suppressor genes supports the notion that ultraviolet exposure plays an important part in the development of squamous cell carcinoma.

Aged↗

PubMed2001

Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis.

BACKGROUND: To elucidate the molecular mechanism of diabetic nephropathy, a high-density DNA filter array was employed to survey the gene expression profile of streptozotocin-induced diabetic CD-1 (ICR) mouse kidneys. METHODS: Ten-week-old CD-1 male mice were divided into four groups: (1) control, (2) unilaterally nephrectomized (UX) mice, (3) streptozotocin (STZ)-induced diabetic (STZ) mice, and (4) STZ mice with unilateral renal ablation (STZ-UX). Pathological changes were examined at 24 weeks after the induction. The gene expression profile was compared between the control and STZ mice by a Gene Discovery Array (GDA). RESULTS: The glomeruli in UX mouse kidney showed prominent glomerular hypertrophy, while the accumulation of mesangial matrix was minimal. Both STZ and STZ + UX mice had significant glomerular hypertrophy and glomerulosclerosis, and the lesions were not enhanced by renal ablation. By comparison between control and STZ mice, 16 clones that increased in expression with the induction of diabetes and 65 clones that decreased in diabetic kidneys were identified. The 37 known genes were related to glucose and lipid metabolism, ion transport, transcription factors, signaling molecules, and extracellular matrix-related molecules. The genes known to be involved in cell differentiation and organogenesis in various tissues (that is, Unc-18 homolog, POU domain transcription factor 2, lunatic fringe gene homolog, fibrous sheath component 1, Sox-17, fibulin 2, and MRJ) were found to be differentially expressed in the early phase of diabetic kidneys. CONCLUSIONS: Hyperglycemia is a major determinant of glomerulosclerosis in STZ-induced diabetic CD-1 mice, and the altered gene expression in the early phase of diabetic kidney may be critical for the development of diabetic nephropathy.

Animals↗

PubMed2001

Correlation of peripheral venous pressure and central venous pressure in surgical patients.

OBJECTIVE: To determine the degree of agreement between central venous pressure (CVP) and peripheral venous pressure (PVP) in surgical patients. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Patients without cardiac dysfunction undergoing major elective noncardiac surgery (n = 150). MEASUREMENTS AND MAIN RESULTS: Simultaneous CVP and PVP measurements were obtained at random points in mechanically ventilated patients during surgery (n = 100) and in spontaneously ventilating patients in the postanesthesia care unit (n = 50). In a subset of 10 intraoperative patients, measurements were made before and after a 2-L fluid challenge. During surgery, PVP correlated highly to CVP (r = 0.86), and the bias (mean difference between CVP and PVP) was -1.6 +/- 1.7 mmHg (mean +/- SD). In the postanesthesia care unit, PVP also correlated highly to CVP (r = 0.88), and the bias was -2.2 +/- 1.9 (mean +/- SD). When adjusted by the average bias of -2, PVP predicted the observed CVP to within +/-3 mmHg in both populations of patients with 95% probability. In patients receiving a fluid challenge, PVP and CVP increased similarly from 6 +/- 2 to 11 +/- 2 mmHg and 4 +/- 2 to 9 +/- 2 mmHg. CONCLUSION: Under the conditions of this study, PVP showed a consistent and high degree of agreement with CVP in the perioperative period in patients without significant cardiac dysfunction. PVP -2 was useful in predicting CVP over common clinical ranges of CVP. PVP is a rapid noninvasive tool to estimate volume status in surgical patients.

Aged↗

PubMed2001

UV-specific p53 and PTCH mutations in sporadic basal cell carcinoma of sun-exposed skin.

UVB irradiation is known to produce DNA damage at mutation hotspots in the p53 tumor suppressor gene, leading to the development of skin cancers. Mutations in the PTCH tumor suppressor gene, which is known to be responsible for the development of nevoid basal cell carcinoma syndrome, have also been identified in sporadic basal cell carcinomas (BCCs). We describe the case of an 80-year-old welder in whom 3 novel p53 mutations, as well as UV-specific PTCH mutations, were detected in two BCC samples from sun-exposed skin. The simultaneous presence of UV-specific p53 and PTCH mutations in the same BCC sample has not previously been reported.

Aged↗

PubMed2001

Evaluation of the ELOVL4 gene in patients with age-related macular degeneration.

Stargardt-like macular degeneration (STGD(3)) and autosomal dominant macular degeneration (adMD) share phenotypic characters with atrophic age-related macular degeneration (AMD). Mutations in a photoreceptor cell-specific factor involved in the elongation of very long chain fatty acids (ELOVL(4)) were shown to be associated with STGD(3), adMD, and pattern dystrophy. We screened 778 patients with AMD and 551 age-matched controls to define the role of sequence variants in the ELOVL(4) gene in age-related macular degeneration. We detected three sequence variants in the non-coding region and eight variants in the coding region. No statistically significant association was observed between sequence variants in the ELOVL(4) gene and susceptibility to AMD. However, for the detection of modest effects of multiple alleles in a complex disease, the analysis of larger cohorts of patients may be required.

Age Factors↗

PubMed2001

Performance evaluation of laser-induced breakdown spectrometry as a multimetal continuous emission monitor.

Laser-induced breakdown spectroscopy (LIBS) has been evaluated as a multimetal continuous emissions monitor (CEM) at the U.S. Environmental Protection Agency (EPA) rotary kiln incinerator simulator (RKIS) facility in Raleigh, NC. Two detection systems with a bifurcated optical fiber bundle were used for simultaneously monitoring the concentrations of Be, Cd, Cr, and Hg in the test. Two calibration techniques were evaluated in the laboratory for the field measurements. On-line calibration of relative metal concentration was also performed in the simulated incinerator gas stream. Toxic metal concentrations measured with LIBS have been compared with the EPA reference method (RM) results.

Air Pollutants↗

PubMed2001

Risk factors for asthma prevalence among urban and nonurban African American children.

Urban residence is a risk factor for asthma. We examined multiple risk factors simultaneously among African American children. We interviewed 2409 African American mothers of newborns who had at least 1 child at home under 18 years of age. Sixteen percent reported at least 1 child with physician-diagnosed asthma. Significantly associated with an asthmatic child were maternal asthma and allergies, maternal cigarette smoking, a humidifying device, and a gas range or oven in the home. Urban residence was related to asthma but became nonsignificant once other factors were controlled for. Asthma associated with urban residence may be explained by identifiable factors.

Black or African American↗

PubMed2001

EXAFS study on the local atomic structures around iron in glycosylated haemoglobin.

Samples with 5.1%, 9.8% and 15.3% HbA1c were extracted from normal subjects and patients with slight and serious diabetes respectively. Extended x-ray absorption fine structure spectra of Fe K absorption were collected at the EXAFS experimental station of the Beijing Synchrotron Radiation Facility. The step-by-step fluorescent mode was employed with a count time of 10 s per point. Several independent scans were averaged to eliminate the statistical noise. Reference backscattering amplitudes and phaseshifts were calculated using the curve wave theory (FEFF code) of EXAFS. Apart from the nitrogen neighbours around the central iron atom, oxygen neighbours are also found. The Fe-N bond length increases by about 0.02 A for the sample with 15.3% HbA1c compared with the others, but the Fe-O bond length is almost unchanged. With increasing of HbA1c concentration, the content of Hb increases and the content of HbO2 decreases. This demonstrates that the glycosylation of haemoglobin will decrease its ability to carry oxygen.

Absorptiometry, Photon↗

PubMed2001

Production, characterization, and epitope mapping of monoclonal antibodies against human polydeoxyribonucleotide kinase.

Polydeoxyribonucleotide kinase (PNK) is a mammalian DNA repair enzyme that has the capacity to phosphorylate 5' DNA termini and dephosphorylate 3' DNA termini. A series of murine monoclonal antibodies (MAbs) was raised against the full-length recombinant human PNK. Seven of these antibodies were selected and characterized by enzyme immunoassay, Western blot analysis, and their capacity to immunoprecipitate PNK. The epitope location was defined by cyanogen bromide digestion and by using a truncated PNK for Western blot analysis. All of the MAbs recognize a single 60-kDa protein in human cell extracts. PNKs from calf, monkey, and Chinese hamster cell and tissue extracts were also detected by some or all of the MAbs. These antibodies can be successfully used for the cellular, biochemical, and functional analysis of PNK in different mammalian cell lines.

Amino Acid Sequence↗

PubMed2001

New mutations in pncA of in vitro selected pyrazinamide-resistant strains of Mycobacterium tuberculosis.

Mutations within the pncA gene can cause pyrazinamide (PZA) resistance in Mycobacterium tuberculosis. To study further the mutational events leading to PZA resistance, a H37Rv PZA-susceptible strain was used to derive PZA-resistant mutants in vitro. This parental strain was grown at gradually increased concentrations of PZA (from 200 up to 500 microg/ml). A total of eight variant strains were selected for further study. PZA resistance was selected at 250 microg/ml or higher. Seven of them lost PZase activity and hence were PZA resistant. The remaining strain has shown a functional PZase and hence was sensitive to PZA after being exposed to 200 microg/ml PZA. Sequence analysis shows different novel mutations within the pncA gene of these variants. Two silent mutations at nucleotide 6 (G --> A) and 300 (C --> T) were found in the PZA-sensitive variant. Among the seven PZA-resistant variants, there were three deletion mutations found at nucleotide 78 (G), 79 (A), and 143 (A), all resulting in a frameshift, and one nonsense mutation at nucleotide 102 (C --> G), creating a stop codon TAG. It was observed that the mutations found in the pncA gene of these PZA-resistant mutants show a distinctive pattern: mutation positions moved toward the beginning of the open reading frame correlating with the increase in PZA concentration, suggesting a possible relationship between the increase of PZA concentration and the early occurrence of mutations on the pncA gene.

Amidohydrolases↗

PubMed2001

Engineering virtual cardiac tissue.

The kinetics of proteins involved in ion transfer, sequestration and binding in cardiac cells can be modelled to construct a model of the electrical activity of isolated cardiac cells as a system of ordinary differential equations. These cell models may be incorporated into tissue models, which, when combined with histology and anatomy, form virtual tissues. The effects of changes in specific protein expression, or changes in protein kinetics, produced by mutations or pharmacological agents, can be simulated using these tissue models and used to account for the whole organ effects of changes in specific ion-transport protein activity.

Action Potentials↗

PubMed2001

An information-based sequence distance and its application to whole mitochondrial genome phylogeny.

MOTIVATION: Traditional sequence distances require an alignment and therefore are not directly applicable to the problem of whole genome phylogeny where events such as rearrangements make full length alignments impossible. We present a sequence distance that works on unaligned sequences using the information theoretical concept of Kolmogorov complexity and a program to estimate this distance. RESULTS: We establish the mathematical foundations of our distance and illustrate its use by constructing a phylogeny of the Eutherian orders using complete unaligned mitochondrial genomes. This phylogeny is consistent with the commonly accepted one for the Eutherians. A second, larger mammalian dataset is also analyzed, yielding a phylogeny generally consistent with the commonly accepted one for the mammals. AVAILABILITY: The program to estimate our sequence distance, is available at http://www.cs.cityu.edu.hk/~cssamk/gencomp/GenCompress1.htm. The distance matrices used to generate our phylogenies are available at http://www.math.uwaterloo.ca/~mli/distance.html.

Animals↗

PubMed2001

Four-dimensional dielectric property image obtained from electron spectroscopic imaging series.

We have demonstrated a new quantitative method to characterize two-dimensional distributions of energy-dependent dielectric function of materials from low loss electron spectroscopic image (ESI) series. Two problems associated with extracted image-spectrum from the low-loss image series, under-sampling and loss of energy resolution, were overcome by using fast Fourier transformation (FFT) interpolation and maximum entropy deconvolution method. In this study, Black Diamond/Si3N4/SiO2/Si-substrate dielectric layer designed for copper metallization was used as the sample. We show that the reconstructed (FFT interpolated and maximum entropy deconvoluted) image-spectrum obtained from ESI series images can be quantified with the same accuracy as conventional electron energy-loss spectroscopy spectra. Since the analysis of the dielectric function is sensitive to the local thickness of the specimen using Kramers-Kronig analysis, we also developed a new method to quantitatively determine the dielectric constant for low-k materials. We have determined the thickness of the Black Diamond using the extrapolated thickness method from the materials of known dielectric constants. Using Kramers-Kronig formula, the dielectric function map can be deduced from two-dimensional reconstructed single scattering spectra with providing the information of thickness. We proposed a four-dimensional data presentation for revealing the uniformity of the energy dependent property. The accuracy of our methods depends on the thickness determination and on the quality of the reconstructed spectra from the image series.

Journal Article↗

PubMed2001

Lysophosphatidylcholine enhances carotenoid uptake from mixed micelles by Caco-2 human intestinal cells.

Despite the interest in the beneficial roles of dietary carotenoids in human health, little is known about their solubilization from foods to mixed bile micelles during digestion and the intestinal uptake from the micelles. We investigated the absorption of carotenoids solubilized in mixed micelles by differentiated Caco-2 human intestinal cells, which is a useful model for studying the absorption of dietary compounds by intestinal cells. The micelles were composed of 1 micromol/L carotenoids, 2 mmol/L sodium taurocholate, 100 micromol/L monoacylglycerol, 33.3 micromol/L fatty acid and phospholipid (0-200 micromol/L). The phospholipid content of micelles had profound effects on the cellular uptake of carotenoids. Uptake of micellar beta-carotene and lutein was greatly suppressed by phosphatidylcholine (PC) in a dose-dependent manner, whereas lysophosphatidylcholine (lysoPC), the lipolysis product of PC by phospholipase A2 (PLA2), markedly enhanced both beta-carotene and lutein uptake. The addition of PLA2 from porcine pancreas to the medium also enhanced the uptake of carotenoids from micelles containing PC. Caco-2 cells could take up 15 dietary carotenoids, including epoxy carotenoids, such as violaxanthin, neoxanthin and fucoxanthin, from micellar carotenoids, and the uptakes showed a linear correlation with their lipophilicity, defined as the distribution coefficient in 1-octanol/water (log P(ow)). These results suggest that pancreatic PLA2 and lysoPC are important in regulating the absorption of carotenoids in the digestive tract and support a simple diffusion mechanism for carotenoid absorption by the intestinal epithelium.

Bile Acids and Salts↗