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Biomedical subjects

Y H Zhao

Publications and source records attributed to Y H Zhao.

At least 19 recordsLinked to original sources

Compact and dissociated dislocations in aluminum: implications for deformation.

Atomistic simulations, confirmed by electron microscopy, show that dislocations in aluminum can have compact or dissociated cores. The calculated minimum stress (sigma(P)) required to move an edge dislocation is approximately 20 times smaller for dissociated than for equivalent compact dislocations. This contradicts the well accepted generalized stacking fault energy paradigm that predicts similar sigma(P) values for both configurations. Additionally, Frank's rule and the Schmid law are also violated because dislocation core energies become important. These results may help settle a 50-year-old puzzle regarding the magnitude of sigma(P) in face-centered-cubic metals, and provide new insights into the deformation of ultra-fine-grained metals.

Journal Article↗

Retrograde cerebral perfusion of oxygenated, compacted red blood cells attenuates brain damage after hypothermia circulation arrest of rat.

BACKGROUND: It was proved that higher haematocrit (Hct) might improve the function of brain after hypothermia circulation arrest (HCA). In the present study we established a new rat HCA model and investigated whether retrograde cerebral perfusion of oxygenated, compacted red blood cells (RBC) could attenuate brain injury after HCA. METHODS: A new rat HCA model was developed and rats were randomly distributed into three groups: HCA group, HCA combined with retrograde cerebral perfusion of oxygenated, compacted red blood cell group (HCArcp group), and sham operation group (sham op. group). Animals both in the HCA group and in the HCArcp group underwent HCA 90 min at 18 degrees C. Brain damage after HCA was evaluated with light microscopy and electron microscopy. Immunohistochemistry and RT-PCR techniques were used to measured the different expressions of the C-Fos, Bcl-2, Bax mRNA and protein among the groups. Additionally we measured the wet/dry ratio of the brain in order to evaluate the oedema degree after HCA. RESULTS: The new HCA model of rat we developed was comparable to the clinical setting not only in terms of the intubation, anaesthesia method and materials employed but also in terms of the priming volume in relation to body weight. The number of injured neurones in the hippocampus CA1 and parietal cortex, but not in the thalamus of the HCA group, was significantly greater than that of the HCArcp group (P<0.05). The mean score of mitochondrion of the hippocampus CA1 in the HCA group was significantly higher than in the HCArcp group (P<0.05). The expression of C-Fos, Bax mRNA and protein in the hippocampus CA1 and/or parietal cortex area was higher in the HCA group than in the HCArcp group (P<0.05). Expression of the mRNA and protein of Bcl-2 was higher in the HCArcp group than in the HCA group (P<0.05). The degree of oedema after HCA between the HCA group and HCArcp group had no significant difference (P>0.05). CONCLUSIONS: We established a new rat model of HCA comparable to the clinical setting. Retrograde cerebral perfusion of oxygenated, compacted RBC is a simple, effective, and safe method to protect the brain during HCA. Adjusting the gene expression in relation to apoptosis might contribute to the neuroprotective effects of a retrograde cerebral infusion of oxygenated, compacted RBC.

Analysis of Variance↗

Ultralong single-wall carbon nanotubes.

Since the discovery of carbon nanotubes in 1991 by Iijima, there has been great interest in creating long, continuous nanotubes for applications where their properties coupled with extended lengths will enable new technology developments. For example, ultralong nanotubes can be spun into fibres that are more than an order of magnitude stronger than any current structural material, allowing revolutionary advances in lightweight, high-strength applications. Long metallic nanotubes will enable new types of micro-electromechanical systems such as micro-electric motors, and can also act as a nanoconducting cable for wiring micro-electronic devices. Here we report the synthesis of 4-cm-long individual single-wall carbon nanotubes (SWNTs) at a high growth rate of 11 microm s(-1) by catalytic chemical vapour deposition. Our results suggest the possibility of growing SWNTs continuously without any apparent length limitation.

Microscopy, Atomic Force↗

In silico cloning of mouse Muc5b gene and upregulation of its expression in mouse asthma model.

Using a BLAST-searching approach, we identified a mouse expressed sequence tag (EST) clone (AA038672) showing great similarity to the 3' end of the human MUC5B gene. The clone was named "3pmmuc5b-1" after complete nucleotide sequencing (Genbank Accession, AF369933). A subsequent search of the mouse genome database with the 3pmmuc5b-1 sequence identified two overlapping genomic clones (AC020817 and AC020794) that contained the sequence of both 3pmmuc5b-1 and the mouse Muc5ac gene. Like their human homologs, the genomic order of the mouse Muc genes is 5'-Muc5ac-Muc5b-3'. These results suggest that the newly identified EST clone, 3pmmuc5b-1, is part of the 3' portion of the mouse Muc5b gene. In situ hybridization demonstrated that this putative mouse Muc5b message was expressed in a restricted manner in the sublingual gland region of the tongue and the submucosal gland region of the mouse trachea in a normal animal. However, the gene expression was greatly enhanced in airway surface epithelium and the submucosal gland region in ovalbumin-induced asthmatic mice. These results were consistent with previous studies of human airway tissues. We therefore conclude that this newly cloned mouse Muc5b gene could be used as a marker for studying aberrant mucin gene expression in mouse models of various airway diseases.

Animals↗

Characterization of a novel airway epithelial cell-specific short chain alcohol dehydrogenase/reductase gene whose expression is up-regulated by retinoids and is involved in the metabolism of retinol.

Multiple retinoic acid responsive cDNAs were isolated from a high density cDNA microarray membrane, which was developed from a cDNA library of human tracheobronchial epithelial cells. Five selected cDNA clones encoded the sequence of the same novel gene. The predicted open reading frame of the novel gene encoded a protein of 319 amino acids. The deduced amino acid sequence contains four motifs that are conserved in the short-chain alcohol dehydrogenase/reductase (SDR) family of proteins. The novel gene shows the greatest homology to a group of dehydrogenases that can oxidize retinol (retinol dehydrogenases). The mRNA of the novel gene was found in trachea, colon, tongue, and esophagus. In situ hybridization of airway tissue sections demonstrated epithelial cell-specific gene expression, especially in the ciliated cell type. Both all-trans-retinoic acid and 9-cis-retinoic acid were able to elevate the expression of the novel gene in primary human tracheobronchial epithelial cells in vitro. This elevation coincided with an enhanced retinol metabolism in these cultures. COS cells transfected with an expression construct of the novel gene were also elevated in the metabolism of retinol. The results suggested that the novel gene represents a new member of the SDR family that may play a critical role in retinol metabolism in airway epithelia as well as in other epithelia of colon, tongue, and esophagus.

3-Hydroxysteroid Dehydrogenases↗

Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure-activity relationship (QSAR) with the Abraham descriptors.

The human intestinal absorption of 241 drugs was evaluated. Three main methods were used to determine the human intestinal absorption: bioavailability, percentage of urinary excretion of drug-related material following oral administration, and the ratio of cumulative urinary excretion of drug-related material following oral and intravenous administration. The general solvation equation developed by Abraham's group was used to model the human intestinal absorption data of 169 drugs we considered to have reliable data. The model contains five Abraham descriptors calculated by the ABSOLV program. The results show that Abraham descriptors can successfully predict human intestinal absorption if the human absorption data is carefully classified based on solubility and administration dose to humans.

Administration, Oral↗

QSAR study on the toxicity of substituted benzenes to the algae (Scenedesmus obliquus).

50% effective inhibition concentration 48h-EC50 of 40 substituted benzenes to the algae (Scenedesmus obliquus) was determined. The energy of the lowest unoccupied molecular orbital (E(LUMO)) was calculated by the quantum chemical method MOPAC6.0-AM1. By using E(LUMO) and the hydrophobicity parameter log K(OW) the quantitative structure-activity relationship model (QSAR) was developed: log1/EC50=0.272 logK(OW) - 0.659E(LUMO) + 2.54, R2 = 0.793, S.E. = 0.316, F = 71.07, n = 40. A series of equations were obtained about the measured EC50 values of different subclasses of compounds. For those compounds containing double -NO2, their toxicity may be related chiefly to the intracellular reduction of -NO2 obtaining electron, while for anilines and phenols, K(OW) contributes most to the QSAR and E(LUMO) very little.

Benzene Derivatives↗

Correlation and prediction of a large blood-brain distribution data set--an LFER study.

We report linear free energy relation (LFER) models of the equilibrium distribution of molecules between blood and brain, as log BB values. This method relates log BB values to fundamental molecular properties, such as hydrogen bonding capability, polarity/polarisability and size. Our best model of this form covers 148 compounds, the largest set of log BB data yet used in such a model, resulting in R(2)=0.745 and e.s.d.=0.343 after inclusion of an indicator variable for carboxylic acids. This represents rather better accuracy than a number of previously reported models based on subsets of our data. The model also reveals the factors that affect log BB: molecular size and dispersion effects increase brain uptake, while polarity/polarisability and hydrogen-bond acidity and basicity decrease it. By splitting the full data set into several randomly selected training and test sets, we conclude that such a model can predict log BB values with an accuracy of less than 0.35 log units. The method is very rapid-log BB can be calculated from structure at a rate of 700 molecules per minute on a silicon graphics O(2).

Blood-Brain Barrier↗

Differential regulation of airway mucin gene expression and mucin secretion by extracellular nucleotide triphosphates.

The effects of extracellular nucleotide triphosphates on the stimulation of mucin production by airway epithelial cells were examined. The order of potency in stimulating mucin secretion in primary cultures of human tracheobronchial epithelial cells is: uridine 5'-triphosphate (UTP) approximately equal to adenosine 5'-triphosphate (ATP) approximately equal to ATP-gamma-S > uridine 5'-diphosphate approximately equal to adenosine 5'-diphosphate > alpha,beta-methylene ATP >> adenosine. However, only UTP can increase mucin gene (MUC5AC, MUC5B) expression; ATP and other analogues have no stimulatory effect. The stimulation of MUC5AC and MUC5B expression by UTP is time- and dose-dependent. A similar effect on the elevation of mucous cell population in mouse airway epithelium can be demonstrated in vivo by an intratracheal instillation of UTP-saline solution. The stimulatory effect of UTP or ATP on mucin secretion was inhibited by pertussis toxin, U73122, and Calphostin C, but not by PD98059, suggesting a G-protein/ phospholipase (PL) C/protein kinase (PK) C-dependent and mitogen-activated protein kinase (MAPK)-independent signaling pathway. However, the stimulatory effect of UTP on mucin gene expression was sensitive to pertussis toxin and PD98059, but not to Calphostin C and U73122, suggesting a G-protein/MAPK-dependent and PLC/PKC-independent signaling pathway. These findings are the first demonstration that UTP, a pyrimidine nucleotide triphosphate, can enhance both mucin secretion and mucin gene expression through different signaling pathways.

Adenosine Triphosphate↗

Characterization of human mucin 5B gene expression in airway epithelium and the genomic clone of the amino-terminal and 5'-flanking region.

Human mucin (MUC) 5B gene expression in human airway epithelium was studied in both tissue sections and cultures of tracheobronchial epithelial (TBE) cells. In situ hybridization demonstrated that MUC5B message was expressed mainly in the mucous cells of submucosal glands of normal human airway tissues. Nevertheless, an elevated MUC5B message level could be seen in surface goblet cells from patients with airway diseases and inflammation. Regardless of the airway tissue sources, MUC5B message was regulated by all-trans-retinoic acid (RA) and culture conditions in both primary and passage-1 cultures of TBE cells. MUC5B message, to a lesser extent, was also found in the immortalized epithelial cell line HBE1, but not in BEAS-2B cells. To elucidate the molecular mechanism of MUC5B gene expression, a genomic clone was obtained and sequenced for the amino terminal and the 5'-flanking region of MUC5B gene. A luciferase reporter construct containing 4,169 base pairs of the 5'-flanking region of MUC5B gene demonstrated a cell type-specific basal promoter activity in transfection studies. Both RA and the air-liquid interface culture condition further enhanced this promoter activity. These results suggest that the 5'-flanking region of MUC5B gene contains cis-elements that are potentially involved in the regulation of MUC5B gene expression.

5' Flanking Region↗

[Research of ultra-structural pathological changes of nervous, endocrine and immune system in heroin addicts].

OBJECTIVE: To investigate ultrastructural pathological changes of Heroin-Addicts. METHODS: Heroin-Addicts' central nervous system, endocrine system, immune system and reproductive system in 4 cases are observed by using transmission electron microscope(TEM). RESULTS: The changes of central nervous system are mitochondrion swelling, crista fragmentation and disappear. Endoplasmic reticulum dilation, nervous fibres and cell organelles reduction; mitochondrion swelling, Partial crista fragmentation and endoplasmic reticulum dilation are also found in endocrine system; Lymphocytes reduction, cytoplasm ingredient reduction and dead lymphocytes increase in immune system; in reproductive system, spermatogenic cells and cell organelles are reduced in the male and follicle disappeared in the female. CONCLUSION: Ultra-structural pathological changes of heroin-addicts are presented acute, chronic oxygen deficiency degeneration and necrosis.

Central Nervous System↗

[AVP-ergic mechanism in the rostral ventrolateral medulla:a possible role in stress-induced hyperviscosity].

The study was undertaken to find whether microinjection of vasopressin (AVP) into the rostral ventrolateral medulla (rVLM) affects blood pressure (BP) and blood viscosity in rats and to analyze the effects of AVP-ergic mechanism in the rVLM on stress-induced hyperviscosity of rats. The results are as follows. (1) Microinjection of AVP into the rostral ventrolateral medulla (rVLM) of normal rats resulted in a significant increase in BP and plasma viscosity, which was blocked by bilateral microinjection of AVP V(1) receptor antagonist (d(CH2)5 Tyr(Me)(2) AVP) into the same area. (2) The stress-induced pressor response and hyperviscosity was abolished by microinjection of AVP V(1) receptor antagonist into the rVLM, but not by AVP V(2) receptor antagonist ( adamantaneacetyl(1),O-Et-D-Tyr(2),Val(4),aminobutyryl(6),Arg(8,9) -vasopressin). Microinjection of AVP V(1) receptor antagonist of the same dosage into bilateral caudal ventrolateral medulla (cVLM) or intravenous injection of the antagonist of the same dosage had no effect. The above results suggest that the increase of BP and plasma viscosity induced by microinjection of AVP into rVLM and the stress-induced pressor response and hyperviscosity caused by restraining may be mediated by activation of the AVP V(1) receptor in the rVLM.

Animals↗

Differential expression of stress proteins in nonhuman primate lung and conducting airway after ozone exposure.

The presence of seven stress proteins including various heat shock proteins [27-kDa (HSP27), 60-kDa (HSP60), 70-kDa (HSP70) and its constitutive form HSC70, and 90-kDa (HSP90) HSPs] and two glucose-regulated proteins [75-kDa (GRP75) and 78-kDa (GRP78) GRPs] in ozone-exposed lungs of nonhuman primates and in cultured tracheobronchial epithelial cells was examined immunohistochemically by various monoclonal antibodies. Heat treatment (42 degrees C) resulted in increased HSP70, HSP60, and HSP27 and slightly increased HSC70 and GRP75 but no increase in GRP78 in primary cultures of monkey tracheobronchial epithelial cells. Ozone exposure did not elevate the expression of these HSPs and GRPs. All of these HSPs including HSP90, which was undetectable in vitro, were suppressed in vivo in monkey respiratory epithelial cells after ozone exposure. Both GRP75 and GRP78 were very low in control cells, and ozone exposure in vivo significantly elevated these proteins. These results suggest that the stress mechanism exerted on pulmonary epithelial cells by ozone is quite different from that induced by heat. Furthermore, differences between in vitro and in vivo with regard to activation of HSPs and GRPs suggest a secondary mechanism in vivo, perhaps related to inflammatory response after ozone exposure.

Animals↗

QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and carp.

The toxicities of benzoic acids to Vibrio fischeri, Daphnia magna and carp were measured. The results showed that the toxicity to V. fischeri and Daphnia decreased in the order of bromo > chloro > fluoro approximately equal to aminobenzoic acids. The toxicity of substituted benzoic acids to carp and Daphnia was much lower that to V. fischeri. The results also showed that the toxicity of benzoic acids to Daphnia decreased as the pH increased. It is suggested that ionized and non-ionized forms have different toxic responses. The non-ionized form may play an important role in toxicity because the toxicity of benzoic acids to Daphnia greatly decreases as the pH increases. The toxicity of benzoic acids to Daphnia may operate through non-polar narcosis, based on the regression results between the toxicities and partition coefficients (log P) and apparent partition coefficients (log D). However, toxicity cannot be predicted from non-polar baseline models because the ionized and non-ionized form of benzoic acids have different contributions to toxicity. Compared with the single descriptors, the prediction of toxicity of the benzoic acids was improved remarkably by using log P with pKa and log P with ELUMO. For the toxicity of benzoic acids to V. fischeri, it is suggested that the toxic mechanism may be different from the mechanism in Daphnia and carp. A probable reason is that V. fischeri is a unicellular organism with low lipid content, and hence both ionized and non-ionized forms of benzoic acids can easily cross the cell membrane and contribute to toxicity.

Animals↗

Growth and differentiation of conducting airway epithelial cells in culture.

The development of routine techniques for the isolation and in vitro maintenance of conducting airway epithelial cells in a differentiated state provides an ideal model to study the factors involved in the regulation of the expression of mucociliary differentiation. Several key factors and conditions have been identified. These factors and conditions include the use of biphasic culture technique to achieve mucociliary differentiation, the use of such stimulators as the thickness of collagen gel substratum, the calcium level, and vitamin A, and such inhibitors as the growth factors, epidermal growth factor and insulin, and steroid hormones, for mucous cell differentiation. Using the defined culture medium, the life cycle of the mucous cell population in vitro has been investigated. It was demonstrated that the majority of the mucous cell population in primary cultures is not involved in the replication of deoxyribonucleic acid (DNA). However, the mucous cell type is capable of self-renewal in culture, and this reproduction is vitamin A dependent. Furthermore, differentiation from nonmucous to mucous cell type can be demonstrated by adding back a positive regulator such as vitamin A to the "starved" culture. Cell kinetics data suggest that vitamin A-dependent mucous cell differentiation in culture is a DNA replication-independent process, and the process is inhibited by transforming growth factor-beta1.

Cell Differentiation↗