Biomedical subjects

Bin Zhang

Publications and source records attributed to Bin Zhang.

At least 127 records · Page 7Linked to original sources

PubMed2005

The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults.

BACKGROUND: Cyclooxygenase-2 (COX-2) selective inhibitors have been marketed since 1999 as safer alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs). Debate about their cardiac safety has culminated in the recent withdrawal of rofecoxib. Additional studies are needed to better understand this risk and to determine whether this safety concern represents a class effect. OBJECTIVE: To assess the influence of various NSAIDs on the risk for a first myocardial infarction (MI). DESIGN: Population-based, retrospective cohort study analyzed using a time-matched, nested case-control approach. SETTING: Quebec, Canada. PARTICIPANTS: 113,927 elderly persons without previous MI and newly treated with an NSAID between 1 January 1999 and 30 June 2002. MEASUREMENTS: NSAID exposure and occurrence of MI assessed by using Quebec's administrative health databases. RESULTS: Compared with no use of NSAIDs in the year preceding the event, current use of rofecoxib was associated with an increased risk for an acute MI (rate ratio [RR], 1.24 [95% CI, 1.05 to 1.46]) that was more pronounced at higher doses (RR, 1.73 [CI, 1.09 to 2.76]). The concomitant use of aspirin appears to decrease the risk associated with low-dose rofecoxib (RR, 1.00 [CI, 0.77 to 1.28]) but not with high-dose rofecoxib (RR, 2.36 [CI, 1.27 to 4.39]). No increased risks were observed with celecoxib (RR, 0.99 [CI, 0.85 to 1.16]) or the other NSAIDs. LIMITATIONS: The study could not completely account for all potential confounders, including over-the-counter use of aspirin and ibuprofen. CONCLUSIONS: These results provide evidence of an increased risk for acute MI in current users of rofecoxib among elderly persons with no history of MI. This risk appears greater at higher doses. Aspirin use mitigates the risk associated with low-dose but not high-dose rofecoxib. There was no evidence of an increased risk with the other NSAIDs.

Aged↗

PubMed2005

Mouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degeneration.

Transgenic (Tg) mice overexpressing human wild-type alpha-synuclein in oligodendrocytes under the control of the 2,' 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter are shown here to recapitulate features of multiple system atrophy (MSA), including the accumulation of filamentous human alpha-synuclein aggregates in oligodendrocytes linked to their degeneration and autophagocytosis of myelin. Significantly, endogenous mouse alpha-synuclein also accumulated in normal and degenerating axons and axon terminals in association with oligodendroglia and neuron loss and slowly progressive motor impairments. Our studies demonstrate that overexpression of alpha-synuclein in oligodendrocytes of mice results in MSA-like degeneration in the CNS and that alpha-synuclein inclusions in oligodendrocytes participate in the degeneration of neurons in MSA.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

PubMed2005

Synthesis and characterization of a porous magnetic diamond framework, Co3(HCOO)6, and its N2 sorption characteristic.

[Co3(HCOO)6](CH3OH)(H2O) (1), the isostructural analogue of the porous magnet of coordination framework [Mn3(HCOO)6](CH3OH)(H2O), and its desolvated form [Co3(HCOO)6] (2) were prepared and characterized by X-ray and neutron diffraction methods, IR, thermal analyses, and BET, and their magnetic properties were measured. The parent compound, 1, crystallizes in the monoclinic system, space group P21/c, a = 11.254(2) A, b = 9.832(1) A, c = 18.108(3) A, beta = 127.222(2) degrees , V = 1595.5(4) A3, Z = 4, R1 = 0.0329 at 180 K. It possesses a unit cell volume that is 9% smaller than [Mn3(HCOO)6](CH3OH)(H2O) due to the smaller radius of Co2+ ion. Compared with the parent compound 1, the desolvated compound 2 has slightly larger lattice with cell parameters of a = 11.2858(4) A, b = 9.8690(4) A, c = 18.1797(6) A, beta = 127.193(2) degrees , V = 1613.0(1) A3, R1 = 0.0356 at 180 K. The cell parameters of 2, obtained from neutron powder data at 2 K, are a = 11.309(2) A, b = 9.869(1) A, c = 18.201(3) A, beta = 127.244(8) degrees , V = 1617.3(5) A3. The pore volume reduces from 33% to 30% by replacing Mn by Co. The material exhibits a diamond framework based on Co-centered CoCo4 tetrahedral nodes, in which all metal ions have octahedral coordination geometry and all HCOO groups link the metal ions in syn-syn/anti modes. It displays thermal stability up to 270 degrees C. The compound easily loses guest molecules without loss of crystallinity, and it partly reabsorbs water from the atmosphere. Significant N2 sorption was observed for the desolvated framework suggesting that the material possesses permanent porosity. The magnetic properties show a tendency to a 3D long-range magnetic ordering, probably antiferromagnetic with a spin canting arrangement below 2 K.

Journal Article↗

PubMed2005

Axonal transport defects: a common theme in neurodegenerative diseases.

A core pathology central to most neurodegenerative diseases is the misfolding, fibrillization and aggregation of disease proteins to form the hallmark lesions of specific disorders. The mechanisms underlying these brain-specific neurodegenerative amyloidoses are the focus of intense investigation and defective axonal transport has been hypothesized to play a mechanistic role in several neurodegenerative disorders; however, this hypothesis has not been extensively examined. Discoveries of mutations in human genes encoding motor proteins responsible for axonal transport do provide direct evidence for the involvement of axonal transport in neurodegenerative diseases, and this evidence is supported by studies of animal models of neurodegeneration. In this review, we summarize recent findings related to axonal transport and neurodegeneration. Focusing on specific neurodegenerative diseases from a neuropathologic perspective, we highlight discoveries of human motor protein mutations in some of these diseases, as well as illustrate new insights from animal models of neurodegenerative disorders. We also review the current understanding of the biology of axonal transport including major recent findings related to slow axonal transport.

Animals↗

PubMed2005

BACE overexpression alters the subcellular processing of APP and inhibits Abeta deposition in vivo.

Introducing mutations within the amyloid precursor protein (APP) that affect beta- and gamma-secretase cleavages results in amyloid plaque formation in vivo. However, the relationship between beta-amyloid deposition and the subcellular site of Abeta production is unknown. To determine the effect of increasing beta-secretase (BACE) activity on Abeta deposition, we generated transgenic mice overexpressing human BACE. Although modest overexpression enhanced amyloid deposition, high BACE overexpression inhibited amyloid formation despite increased beta-cleavage of APP. However, high BACE expression shifted the subcellular location of APP cleavage to the neuronal perikarya early in the secretory pathway. These results suggest that the production, clearance, and aggregation of Abeta peptides are highly dependent on the specific neuronal subcellular domain wherein Abeta is generated and highlight the importance of perikaryal versus axonal APP proteolysis in the development of Abeta amyloid pathology in Alzheimer's disease.

Alzheimer Disease↗

PubMed2005

Growth inhibition and apoptosis-induced effect on human cancer cells of toosendanin, a triterpenoid derivative from chinese traditional medicine.

Toosendanin, a triterpenoid derivative isolated from the barks of Melia toosendan Sieb et Zucc, has been used as an anthelmintic vermifuge against ascaris for more than fifty years in China. In the present study, we investigated the growth inhibition and apoptosis-induced effect of toosendanin on human cancer cells. The result showed that toosendanin significantly suppressed the proliferation of tested human cancer cell lines. The IC(50) values were less than 1.7 x 10(-7) M and U937 was the most sensitive cell line with a IC(50) of 5.4 x 10(-9) M. Flow cytometric analysis revealed that treatment of U937 cells with toosendanin resulted in a dose- and time-dependent accumulation of cells in the S phase with a concomitant decrease in cells processing to G(0)/G(1) phase. The growth inhibition of U937 cells after exposure to toosendanin was subsequently associated with the induction of apoptosis, as evidence by the typical condensed and fragmented nuclei, DNA fragmentation, and exposure of phosphatidylserine on the outer leaflet of plasma membrane. All these results indicated that toosendanin could serve as a potential candidate for anticancer drug.

Apoptosis↗

PubMed2005

Saturated free fatty acid, palmitic acid, induces apoptosis in fetal hepatocytes in culture.

To investigate the effects of saturated free fatty acid, palmitic acid (PA), on hepatocytes, we administered PA to rat hepatocytes. We demonstrated that PA inhibited the cell growth as a dose- and time-dependent manner in rat hepatocytes. PA-induced morphological changes including swelling, membrane dissolution and formation of debris, and apoptosis with appearance of sub-G1 fraction determined by cell cycle analysis after treatment for 4 days. The level of Bcl-2 was slightly decreased, in contrast, the level of Bax elevated markedly, which resulted in a significant decrease of Bcl-2/Bax ratio after PA treatment on HepG2 cells. These findings demonstrated that PA induces cell death on hepatocytes, perhaps via mitochondria-mediated apoptosis. Furthermore, the present study indicates that PA's cell toxicity may play important roles in the transition from steatosis to steatohepatitis in human especially with obesity.

Animals↗

PubMed2005

The inhibitory effects of synthetic short peptides, mimicking MICA and targeting at NKG2D receptors, on function of NK cells.

NKG2D is an activating receptor expressed on most of human NK cells, one of whose ligands is MICA. Based on the crystal structure of NKG2D-MICA complex, we synthesized three short peptides (P1, P2 and P3), mimicking functional alpha1 and alpha2 domain of MICA. The inhibitory effects of three peptides on NK-92 cells, a human NK cell line against Hela cells were observed and the inhibitory percentage was 38% at maximum for P1+P2+P3 in concentration of 1nM. The same peptides had no effect on NK-92 cell against target cells lacking MICA (K562 cells line). The unrelated peptides as controls had no effect on the system. Two peptides (P2 and P3) were prolonged at one or both ends, and the longer forms of peptides exerted stronger inhibitory effects than their shorter forms. Each combination of two peptides exerted a stronger function than single peptide (P1, P2, P3), indicating that shedding of longer amino acid sequence of alpha1 domain or more domain sites of MICA are better than shorter sequence and fewer sites. P1+P2+P3 revealed the almost same inhibitory rate as the soluble MICA (sMICA). P1+P2+P3 were also able to alleviate the concanavalin A-induced murine autoimmune hepatitis in vivo, conforming the similarity of NKG2D between human and mice. The results demonstrate that MICA-mimicking peptides will be useful to search the specific functional sites for NKG2D-MICA interaction, but also promising in explaining NKG2D-related autoimmunity.

Alanine Transaminase↗

PubMed2005

Doppler waveforms: the relation between ductus venosus and inferior vena cava.

This study was to assess whether or not there was correlation between the Doppler velocity waveform of the ductus venosus (DV) and inferior vena cava (IVC). A total of 142 healthy pregnant women were enrolled and divided into three groups according to the gestational weeks at the examination time. Group 1 was < or = 22 weeks; group 2 was between 22 and 28 weeks; and group 3 was > or = 28 weeks. Acuson 128xp was used to measure the Doppler velocity waveforms of DV and IVC by one experienced examiner. Doppler indices were used for analysis. Our results showed that, with the advance of pregnancy age, the resistance index of DV (DV-RI) and the preload index of IVC (IVC-PLI) were correlated with the gestational weeks, r = -0.247 and r = -0.540, respectively. There was a weak correlation between DV-RI and IVC-PLI, r = 0.202, p < 0.05; however, there was no significant correlation between DV-RI and IVC-PLI in group 1, group 2 or group 3. In conclusion, we report the first study on the correlation between DV-RI and IVC-PLI, which indicated the different roles of DV and IVC in fetal hemodynamics.

Blood Flow Velocity↗

PubMed2005

Impaired rapid eye movement sleep in the Tg2576 APP murine model of Alzheimer's disease with injury to pedunculopontine cholinergic neurons.

Impaired rapid eye movement sleep (REMS) is commonly observed in Alzheimer's disease, suggesting injury to mesopontine cholinergic neurons. We sought to determine whether abnormal beta-amyloid peptides impair REMS and injure mesopontine cholinergic neurons in transgenic (hAPP695.SWE) mice (Tg2576) that model brain amyloid pathologies. Tg2576 mice and wild-type littermates were studied at 2, 6, and 12 months by using sleep recordings, contextual fear conditioning, and immunohistochemistry. At 2 months of age, REMS was indistinguishable by genotype but was reduced in Tg2576 mice at 6 and 12 months. Choline acetyltransferase-positive neurons in the pedunculopontine tegmentum of Tg2576 mice at 2 months evidenced activated caspase-3 immunoreactivity, and at 6 and 12 months the numbers of pedunculopontine tegmentum choline acetyltransferase-positive neurons were reduced in the Tg2576 mice. Other cholinergic groups involved in REMS were unperturbed. At 12 months, Tg2576 mice demonstrated increased 3-nitrotyrosine immunoreactivity in cholinergic projection sites but not in cholinergic soma. We have identified a population of selectively compromised cholinergic neurons in young Tg2576 mice that manifest early onset REMS impairment. The differential vulnerability of these cholinergic neurons to Abeta injury provides an invaluable tool with which to understand mechanisms of sleep/wake perturbations in Alzheimer's disease.

Alzheimer Disease↗

PubMed2005

Response of the lung to pulmonary insulin dosing in the rat model and effects of changes in formulation.

BACKGROUND: The hope that pulmonary insulin will provide increased patient compliance and quality of life has created great interest in patients with diabetes, the medical community, and the general public. A pulmonary insulin product is becoming a reality with clinical trials indicating comparable glycemic control with no change in pulmonary function. However, the longterm effects of pulmonary insulin dosing are not known, and as more pulmonary formulations for insulin and other proteins are rapidly being developed the need for further safety data continues to grow. METHODS: Using gene microarrays, we compared differences in the levels of mRNAs in the lung tissue of rats that were administered a subcutaneous injection or a pulmonary instillation of insulin, as well as rats receiving an pulmonary instillation of insulin and a drug delivery agent. RESULTS: While the insulin doses achieved comparable blood glucose depression and serum insulin concentrations, 30 mRNAs were differentially regulated in response to pulmonary dosing, including 10 mRNAs associated with an immune response and four associated with the lung's response to injury, as well as ion channels and transcription factors. When disodium 8-((N-salicyloyl-2-amino-4-chloro)phenoxy)octanoate, a drug delivery agent known to facilitate pulmonary absorption, was instilled in combination with the pulmonary insulin dose, an attenuation of this response was observed. CONCLUSIONS: These findings suggest that undesirable effects of pulmonary dosing may be avoided by changes in formulation and that further evaluation of the effects of chronic pulmonary administration of insulin is warranted.

Adenosine Deaminase↗

PubMed2005

Pediococcus cellicola sp. nov., a novel lactic acid coccus isolated from a distilled-spirit-fermenting cellar.

Two novel Pediococcus strains, Z-1 and Z-8(T), were isolated from a distilled-spirit-fermenting cellar in Hebei Province, China. The cells were Gram-positive, non-spore-forming, non-motile cocci, occurring in pairs or tetrads. The strains were facultatively anaerobic and produced 50 % (-)-D-/50% (+)-L-lactic acid exclusively from glucose fermentation, but did not produce catalase. Both strains fermented rhamnose, ribose, xylose, lactose, maltose, trehalose and sucrose, and tolerated 10% ethanol. The mean G+C content of the two strains was 38+/-1 mol% (37 mol% for the type strain, Z-8(T)). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain Z-8(T) clustered within the Pediococcus damnosus-Pediococcus inopinatus-Pediococcus parvulus group, with 98.3-98.5% 16S rRNA gene similarity. DNA-DNA relatedness between strain Z-8(T) and P. damnosus LMG 11484(T), P. inopinatus LMG 11409(T) and P. parvulus LMG 11486(T) was 19+/-4, 35+/-5 and 31+/-5%, respectively. Therefore, based on the distinctive phenotypic characteristics, and genotypic and phylogenetic analyses, a novel Pediococcus species, Pediococcus cellicola sp. nov., is proposed. The type strain is Z-8(T) (=AS 1.3787(T)=LMG 22956(T)).

China↗

PubMed2005

Wavelet transform-based frequency tuning ILC.

In this paper, a discrete wavelet transform-based cutoff frequency tuning method is proposed and experimental investigation is reported. In the method, discrete wavelet packet algorithm, as a time-frequency analysis tool, is employed to decompose the tracking error into different frequency regions so that the maximal error component can be identified at any time step. At each time step, the passband of the filter is from zero to the upper limit of frequency region where the maximal error component resides. Hence, the filter is a function of time as well as index of cycle. The experimental results show that this method can suppress higher frequency error components at proper time steps. While at the time steps where the major tracking error falls into lower frequency range, the cutoff frequency of the filter is set lower to reduce the influence of noises and uncertainties. This way, learning transient and long-term stability can be improved.

Algorithms↗

PubMed2005

Role of impaired peritubular capillary and hypoxia in progressive interstitial fibrosis after 56 subtotal nephrectomy of rats.

AIM: To investigate the potential role of peritubular capillary (PTC) loss and subsequent hypoxia as a pathogenic factor in interstitial fibrosis after renal ablation in rats. METHODS: PTC loss and tubulointerstitial hypoxia in remnant kidney rats (SNTx group), sham-operated rats (sham group) and normal animals (normal group) were assessed by peritubular CD141-positive staining lumina and tubulointerstitial hypoxia-inducible factor alpha subunit 1 (HIF-1alpha) expression, respectively, at the time points of week 3, week 6 and week 12. The related cardinal factors contributing to interstitial fibrosis, such as transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA) were also evaluated and analysed in the context of progressive PTC loss. Expression of TGF-beta1 mRNA in cultured renal tubular epithelial cells (MDCK cells) exposed to hypoxia was also investigated. RESULTS: PTC loss and tubulointerstitial hypoxia were noted even in the early stage (week 3) when the interstitial fibrosis was mild, and were persistent in the process of developing interstitial fibrosis. An in vitro study showed that hypoxia enhanced TGF-beta1 mRNA expression in the MDCK cells. CONCLUSION: PTC loss or hypoxic milieu in the tubulointerstitium is a pathological event, which may contribute to the developing interstitial fibrosis mediated by direct hypoxic effects and via hypoxia-induced TGF-beta1 expression.

Actins↗

PubMed2005

Generation of rac3 null mutant mice: role of Rac3 in Bcr/Abl-caused lymphoblastic leukemia.

Numerous studies indirectly implicate Rac GTPases in cancer. To investigate if Rac3 contributes to normal or malignant cell function, we generated rac3 null mutants through gene targeting. These mice were viable, fertile, and lacked an obvious external phenotype. This shows Rac3 function is dispensable for embryonic development. Bcr/Abl is a deregulated tyrosine kinase that causes chronic myelogenous leukemia and Ph-positive acute lymphoblastic leukemia in humans. Vav1, a hematopoiesis-specific exchange factor for Rac, was constitutively tyrosine phosphorylated in primary lymphomas from Bcr/Abl P190 transgenic mice, suggesting inappropriate Rac activation. rac3 is expressed in these malignant hematopoietic cells. Using lysates from BCR/ABL transgenic mice that express or lack rac3, we detected the presence of activated Rac3 but not Rac1 or Rac2 in the malignant precursor B-lineage lymphoblasts. In addition, in female P190 BCR/ABL transgenic mice, lack of rac3 was associated with a longer average survival. These data are the first to directly show a stimulatory role for Rac in leukemia in vivo. Moreover, our data suggest that interference with Rac3 activity, for example, by using geranyl-geranyltransferase inhibitors, may provide a positive clinical benefit for patients with Ph-positive acute lymphoblastic leukemia.

Alleles↗

PubMed2005

Directional bias of neurons in V1 and V2 of strabismic monkeys: temporal-to-nasal asymmetry?

PURPOSE: Strabismus that develops shortly after birth is known to cause temporal-to-nasal eye movement asymmetries under monocular viewing. The neural mechanisms underlying this deficit are not well understood. In the current study, the hypothesis that this eye movement anomaly reflects a similar asymmetry in the directional response properties of neurons in the early stages of cortical processing was examined. METHODS: Strabismus was simulated with optical methods in infant monkeys between 4 and 14 weeks of age. When the monkeys were mature, microelectrode recording experiments were conducted in the primary visual cortex (V1) and visual area 2 (V2). After the spatial frequency of sine wave-grating stimuli for each neuron was optimized, each neuron's responsiveness to 24 directions of stimulus movement was measured. The preferred direction and the strength of directional bias were determined by a vector summation method: RESULTS: There was not an overabundance of neurons in V1 or V2 of strabismic monkeys preferring the temporal-to-nasal direction of stimulus movement. However, the average directional bias was significantly reduced in these strabismic monkeys. Interocular suppression was highly prevalent, and this suppression was stronger and more common in neurons dominated by the ipsilateral eye. CONCLUSIONS: The results suggest that the eye movement asymmetries in strabismic subjects do not result from similar asymmetries in the directional properties of V1 or V2 neurons, but rather reflect impoverished cortical signals to the brain stem nuclei that control eye movements.

Animals↗

PubMed2005

[Therapeutic effect of Bushen Rougan Recipe on hepatic fibrosis in rats].

OBJECTIVE: To study the therapeutic effect of Bushen Rougan Recipe (BSRGR) on hepatic fibrosis in rats. METHODS: Forty male Wistar rats were randomly divided into normal control group (n=10), model group (n=15), and BSRGR-treated group (n=15). Rats in the model and BSRGR-treated groups were administered intraperitoneally with 0.5% dimethylnitrosamine (DMN), 10 mg.kg(-1).d(-1), successive 3 days per week for 4 weeks to induce hepatic fibrosis. Then rats in the above 2 groups were given normal saline and BSRGR (10 ml.kg(-1).d(-1), ig) for another 4 weeks, respectively. Rats in the 3 groups were all executed at the end of the 8th week. The serum total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (A) and globulin (G) were determined and the serum hyaluronic acid (HA), laminin (LN) and collagen IV (IV-C) were measured. RESULTS: The rat model of liver fibrosis was successfully induced by DMN. It was found that the serum TBIL, AST and ALT and the liver fibrosis marks were declined in BSRGR-treated group as compared with those in the model group (P<0.01). The content of total serum protein and the A/G in BSRGR-treated group were both increased as compared with those in the model group (P<0.05). CONCLUSION: BSRGR can be used to treat hepatic fibrosis in rats.

Animals↗

PubMed2005

[Changes in endothelin-1 and calcitonin gene-related peptide in myocardium after severe burn and delayed fluid resuscitation in rats at different altitudes on plateau].

OBJECTIVE: To explore changes in endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP) in the myocardium after severe burn and delayed fluid resuscitation in rats at different altitudes. METHODS: Two hundred and forty male Wistar rats were employed as the experimental models with full-thickness burn of 30% total body surface area (TBSA), and they were randomly divided into three groups: delayed fluid resuscitation group (DFR), immediate fluid resuscitation group (IFR) and control group (CG). Samples of myocardial tissue were harvested at 1 hour, 6 hours, 12 hours, 24 hours, 72 hours, 168 hours postburn respectively. The changes in ET-1 and CGRP contents were determined by means of radio immunological assay. RESULTS: (1)The contents of ET-1 and CGRP in DFR group tended to increase at 6 hours after burn, ET-1 was higher 2.8, 3.6 fold, while CGRP higher by 2.2, 1.5 fold (P<0.01), compared with that of CG respectively at 1517 m and 3840 m. The tendency of rise of ET-1 and CGRP was significantly less conspicuous in IFR group than that in DFR group. (2)The contents of ET-1 in DFR group tended to increase at 6 hours and reached the peak at 24 hours after burn at 1517 m, while the levels reached the peak at 72 hours after burn at 3840 m, and the change lasted for 168 hours in DFR group. The contents of CGRP increased significantly at 6 hours and reached the peak at 12 hours at 1517 m, while they reached the peak at 72 hours after burn at 3840 m. CONCLUSION: The myocardial contents of ET-1 tend to increase significantly with the elevation of altitude after severe burn in rats, but the contents of CGRP increased lagged behind. The result show that the higher the altitude is, the more the exhaustion of protective agents of the myocardium, thus resulting in changes in ET-1/CGRP.

Altitude↗