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Biomedical subjects

H Z Chen

Publications and source records attributed to H Z Chen.

At least 19 recordsLinked to original sources

Study of PMS777, a new type of acetylcholinesterase inhibitor, in human HepG2 cells. Comparison with tacrine and galanthamine on oxidative stress and mitochondrial impairment.

Acetylcholinesterase inhibitors are commonly used as cognitive enhancers for dementia in aged people. Among them, tacrine (THA) but not galanthamine, was shown to exhibit hepatotoxicity which reduces its clinical use. PMS777, both a PAF antagonist and a new potent acetylcholinesterase inhibitor was recently demonstrated to reverse scopolamine-induced amnesia in mice without toxicity. In the present study, the effects of THA, galanthamine and PMS777 were compared in HepG2 cells on the oxidative parameters involved in the reported hepatotoxicity of THA. THA (> or = 10 microM) induced an oxidative stress as shown by elevated ROS and MDA production and by a decrease in GSH level. Moreover, mitochondrial membrane potential and redox status were decreased. At low concentrations (< or =10 microM), there was no significant disturbance. None of the oxidative stress markers was affected by PMS777 up to the maximum concentration tested and it is suggested that PMS777 is not cytotoxic for HepG2 cells. Galanthamine was also without cytotoxicity. Our results suggest that the toxic effect of THA above 10 microM may be caused by drug-induced mitochondrial energization impairment and destabilisation of membrane phospholipids associated with an oxidative stress. In contrast by preventing these dysfunctions, PMS777 could be safer than THA.

Cell Survival↗

Environmental risk factors of young onset Parkinson's disease: a case-control study.

While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests certain environmental factors, such as well water drinking, herbicides and pesticides exposure, and neurotoxins, may trigger the chain of oxidative reactions culminating in the death of dopaminergic neurons in substantia nigra to cause parkinsonism. Most studies to date focused on PD with old age onset. However, there is a peculiar group of parkinsonian patients, the young onset Parkinson's disease (YOPD), in whom the age of onset is before 40. It is intriguing to know whether earlier exposure to the putative neurotoxin(s) may contribute to the earlier onset. We therefore conducted this case-control study in which 60 PD patients, 30 YOPD patients and the same number of age- and sex-matched young controls were included. Using logistic regression, we found well water drinking and head injury were risk factors for the development of YOPD. When YOPD patients were compared with PD, we found head injury and exercise were the significant predictors. Keeping all other variables constant, head injury was a risk factor and exercise appeared to be a protective factor. We conclude early exposure to well water drinking and head trauma may trigger and expedite the appearance of parkinsonian features, but such acceleration may be prevented through regular exercise.

Adult↗

Acid-induced polymerization of the group 5 mite allergen from Dermatophagoides pteronyssinus.

House dust mites are the most important source of indoor allergens and cause allergic diseases. Our studies here suggest that the group 5 allergen from Dermatophagoides pteronyssinus (Der p 5) is monomeric at neutral pH, but forms filaments at low pH. Circular dichroism measurements show Der p 5 is a helical protein, and the protein sequence reveals Der p 5 contains coiled-coil helices. The acid-induced filament assembly could be explained in part by the high content of charged residues (40%) in the coiled-coil structure. Interestingly, some of the known Dermatophagoides allergens also contain a heptad repeat, which could potentially form coiled coils. Therefore, coiled-coil helices may be one of the common structural motifs of mite allergens that contribute to their allergenicity.

Allergens↗

[Studies on the cell suspension culture of Saussarea medusa in a stirred tank bioreactor].

The cell suspension culture of Saussarea medusa in a 2L aerated and agitated bioreactor with a four-pitch-blade impeller was investigated. The effects of agitation speed, aeration and inoculum size on cell growth and flavonoids production were studied and it was found that cells had optimum growth and flavonoids production when cultivated at 75 r/min, 700-1000 L/min and an inoculum of 4.0-5.0 g/L. A high cell biomass of 13.8 g/L and flavonoids production of 416 mg/L were achieved after 12 days of cultivation. Time course study revealed that flavonoids biosynthesis was growth-associated. The studies on aggregates size distribution in the bioreactor showed that the aggregates break-up caused by hydrodynamic stress might adversely affect cell growth and lead to significant reduction of cell biomass and flavonoids production.

Bioreactors↗

NKT cells in the rat: organ-specific distribution of NK T cells expressing distinct V alpha 14 chains.

Rat invariant TCR alpha-chains and NKT cells were investigated to clarify whether CD1d-mediated recognition by NKT cells is conserved further in evolution. Rats had multiple-copies of TRAV14 genes, which can be categorized into two types according to the diversity accumulated in the CDR2 region. Rats retained invariant TCR alpha forms with the homogeneous junctional region similar to mouse invariant TRAV14-J281. The proportion of invariant TCR among V alpha 14+ clones was 12.9% in the thymus and increased in the periphery, 31% in the spleen and 95% in hepatic sinusoidal cells. The invariant TRAV14-J281 was expressed by liver sinusoidal and splenic NKT cells with CD8, CD44high, and TCR V beta 8. Type 1 invariant TCR alpha was expressed more frequently in hepatic lymphocytes, while type 2 invariant TCR alpha was expressed predominantly in the spleen. Both types of cells cytolyzed to and were stimulated to proliferate by CD1d-expressing cells in a CD1d-restricted manner. These results suggested that rat NKT cells bearing distinct V alpha 14 chains are distributed in a tissue-specific pattern. NKT cell populations in rats were more variable than those in mice, indicating that they play novel roles in nature. The implication of the molecular interaction between the structurally diverse invariant TCR alpha and CD1d/ligand complex in different organs is discussed.

Amino Acid Sequence↗

Crystallization and preliminary X-ray diffraction analysis of group 5 mite allergen from Dermatophagoides pteronyssinus.

Crystals of the 14-kDa group 5 allergen from Dermatophagoides pteronyssinus (Der p 5) have been obtained at low pH and diffract to 3-A resolution using a conventional x-ray source. The crystals belong to tetragonal space group P41212 or P43212, with unit cell parameters a = b = 114 A and c = 234 A. A self-rotation search revealed a 432 point symmetry and thus suggested 96 molecules in one unit cell, hence 12 monomers in each asymmetric unit.

Animals↗

Structural organization of rat CD1 typifies evolutionarily conserved CD1D class genes.

The non-major histocompatibility complex (MHC)-encoded CD1 family has recently emerged as a new antigen-presenting system that is distinct from either MHC class I or class II molecules. In the present study, we determined the genomic structure of the rat CD1 locus. It was extremely similar to mouse CD1 genes, especially to CD1D1. The 5' flanking region of the CD1 gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL2-A and NF-IL6. Some regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were absent. It is of interest that a tyrosine-based motif for endosomal localization found in the human CD1b cytoplasmic tail was encoded by a single short exon which was conserved in all CD1 molecules except for CD1a. Southern blot and direct sequencing analyses of inbred rat strains suggested very limited polymorphism in the 5' region where a hydrophobic ligand-binding groove is encoded; a single base substitution resulted in amino acid alteration of alanine (GCT) to valine (GTT) at codon 119. Comparison of the overall exon-intron organization of CD1 genes revealed that the length of the intron was also characteristic to each of the two classes of CD1 genes, classic CD1 and CD1D; such categorization has hitherto been made according to the sequence similarity of the coding region. This finding provides further support for the hypothesis that the two classes have different evolutionary histories. In contrast to the complete absence of the classic CD1 in rats and mice, the entire region of nonpolymorphic CD1D has been conserved through mammalian evolution. Similar functional properties of rodent CD1 and human CD1d are implied.

Amino Acid Sequence↗

Effect of losartan and captopril on expression of cardiac angiotensin II AT1 receptor mRNA in rats following myocardial infarction.

AIM: To study the effects of losartan (Los) and captopril (Cap) treatment on expression of cardiac angiotensin II (Ang) AT1 receptor mRNA in rats following myocardial infarction (MI). METHODS: Twenty-four rats with MI after coronary ligation for 7 d were randomly divided into 4 groups: A) Cap in drinking water, ad lib (2 g.L-1), B) i.g. Los 10 mg.kg-1.d-1, C) i.g. Los 30 mg.kg-1.d-1, and D) placebo for 6 wk. Sham-ligation rats (group E) served as controls. The levels of cardiac Ang AT1 receptor mRNA expression in each group (n = 6) were examined by Dot blot using digoxigenin-labeled cDNA probes. RESULTS: Comparing with reflected peak areas of hybridization positive signals in group D (2640 +/- 201 micron 2), the expression of the cardiac Ang AT1 receptor mRNA was much lower in the 3 treated groups (group A 1360 +/- 134 micron 2, group B 1430 +/- 244 micron 2, group C 1310 +/- 95 micron 2) (P < 0.01). But no difference was found between the 3 treated groups and sham-ligation group (1230 +/- 233 micron 2) (P > 0.05). CONCLUSION: Los and Cap attenuated the increase of cardiac Ang AT1 receptor mRNA expression in rats following MI.

Angiotensin Receptor Antagonists↗

[Protective effect of captopril on cultured rat myocardial cells with anoxia and reoxygenation injury].

The effect of captopril (Cap) on electric activity of cultured rat myocardial cells under anoxia and reoxygenation was studied with standard microelectrode techniques. Results showed that anoxic solution caused lowerings of MDP, APA, and Vmax, and a shortening of APD50. All myocytes revealed multiform arrhythmias, and most cells stopped beating within 30 min, while only 40% of the cells exhibited arrhythmias but none stopped beating in the presence of 40 mg.L-1 under the same condition. During reoxygenation, most cells resumed beating in 10 min but some of these cells stopped beating again. The electric activities in rebeating cells during reoxygenation for 30 min were lower than those in normoxic cells. Cap (40 mg.L-1)-treated cells rebeat quickly after reoxygenation and no cell stopped beating any more, with parameters higher than those in untreated cells. These results demonstrate that Cap yields some beneficial effects on preventing anoxia and reoxygenation injury in cultured rat myocardial cells.

Action Potentials↗

Detection of cytomegalovirus genome by in situ hybridization in paraffin embedded endomyocardial biopsy specimens of viral myocarditis.

Cytomegalovirus (CMV) genes were detected by in situ hybridization in 25 Chinese patients with viral myocarditis (VMC). The positive hybridization signals were found in cardiomyocytes (6 cases, 24%), capillary endothelial cells (4 cases, 16%) and interstitial cells (7 cases, 28%). The difference between VMC and control group (16 cases died of brain trauma and 10 cases of congenital heart diseases was statistically significant. There was no definite pathomorphological relationship between the detection of CMV genes and myocardial lesions. The results suggest that CMV infection may be one of the causes of myocarditis and chronic stimulation of the immune system induced by CMV may be a possible pathogenesis of this disease.

Adolescent↗

[Protective effects of nicorandil on action potentials in anoxia and reoxygenated ventricular myocardium of guinea pig].

Standard microelectrode techniques were used to study the effects of nicorandil (500 mumol.L-1) on action potentials in anoxia and reoxygenated ventricular myocardium of guinea pig. The main results: (a) Nicorandil shortened the action potentials duration (APD) and increased the ratio of effective refractory period (ERP) to APD90 (ERP/APD90). It did not cause significant changes in resting potential (RP), the maximal rate of rise of phase 0 (Vmax) and action potential amplitude (APA); (b) Exposure of the preparation to anoxic conditions (hypoxia, acidosis, glucose deprivation, and hyperkalemia) for 20 min, resulted in a marked depolarization of RP, a shortening of APD, reductions of APA and Vmax, and an increase in the ratio of ERP/APD90; (c) Nicorandil did not produce any additional effect on these parameters during anoxia except aggravated shortening of APD; (d) The changes of action potential parameters during anoxia were all completely reversed when the preparation was reoxygenated in the absence of the drug for 20 min. In the presence of the drug, however, APD was only partially reversed; (e) Nicorandil decreased the incidence of abnormal automaticity occurring during reoxygenation from 14/16 to 4/16. It is concluded that nicorandil antagonizes the cellular mechanisms which underlie the reoxygenation arrhythmias and prevent the reoxygenation-induced arrhythmias.

Action Potentials↗