Biomedical subjects

Z Tan

Publications and source records attributed to Z Tan.

At least 37 records · Page 2Linked to original sources

PubMed2001

[Down-regulation of ETA receptor of vascular smooth muscle cells by 17 beta-estradiol].

In the present study, the effects of 17 beta-estradiol on vascular reactivity of ovariectomized rats and proliferation of cultured rat aortic smooth muscle cells were studied. The vascular reactivity was significantly increased in ovariectomized rats compared with the sham-operated animals. The selective ETA receptor antagonist BQ123 inhibited the increase in [3H]-TdR incorporation in response to ET-1 on vascular smooth muscle cells (VSMCs). 17 beta-estradiol also attenuated the ET-1 effects in a dose-dependent manner. The results of RT-PCR and Western blot show that expression of ETA receptor was decreased after treatment with 17 beta-estradiol. The effect of 17 beta-estradiol was partially inhibited by estrogen receptor antagonist tamoxifen. The above results demonstrate that proliferation of VSMCs stimulated by ET-1 was mainly mediated through ETA receptor. Due to the down-regulation of ETA receptor and mediation of estrogen receptor, 17 beta-estradiol inhibits the ET-1-induced proliferation of VSMCs and decreases the vascular reactivity of ovariectomized rats.

Animals↗

PubMed2001

[Glutamate induced modulation of free Ca2+ in isolated inner hair cells of the guinea pig cochlea].

OBJECTIVE: To investigate the modulation effect of glutamate (Glu) on intracellular free Ca2+ concentration([Ca2+]i) of inner hair cell (IHC). METHODS: Using the laser scanning confocal microscope (LSCM), the exogenous Glu-induced changes in [Ca2+]i of isolated 10 IHCs and 10 OHCs of guinea pig cochlea were observed with fluo-3, a fluorescent probe for [Ca2+]i. RESULTS: The IHCs were identified by their unique flask shape with a distinct neck and spherical base and a large spherical nucleus. In most cases, normal cell shapes could be maintained about two hours after isolation. The images of [Ca2+]i from LSCM were similar to those from inverted microscopy. Fluorescence of Fluo-3 distributed in the isolated IHCs with brighter staining in the nucleus. In the presence of low concentration of Glu (3.85 mumol/L), there was an increase of [Ca2+]i in IHCs, whereas no change in OHCs was found. Of the 10 IHCs, increases of [Ca2+]i were observed in 9 and no change in 1. Of the 10 OHCs, 7 showed no [Ca2+]i change and only 3 showed minor reduction of [Ca2+]i. An increase of the Glu concentration (21.88 mumol/L) induced a corresponding increase of [Ca2+]i in IHCs, but eventually resulted in a gradual decrease of [Ca2+]i with a distortion of the normal shape, which indicated that the IHCs were degenerated and swelling. CONCLUSION: These results suggested that exogenous Glu is capable of modulating [Ca2+]i of IHC and may be act on autoreceptor in a positive feedback manner. Excessive Glu induced the accumulation of IHC [Ca2+]i which finally resulted in the degeneration and edema of IHC and the reduction of IHC [Ca2+]i.

Animals↗

PubMed2000

Chemical hypoxia-ischemia induces apoptosis in cerebromicrovascular endothelial cells.

Cerebral endothelial cell (CEC) death from ischemia may exacerbate brain injury by altering microvascular integrity, but little is known concerning the pattern of CEC death and disruption of tight junction between two CECs to ischemia. To address these questions, CECs were isolated from bovine, cultured, and placed in glucose-free medium containing sodium cyanide. Trypan blue staining shown that sodium cyanide resulted in a dose-dependent insult of CECs (10-80 mM). CEC injury increased progressively with the duration of 20 mM cyanide exposure, becoming significant (71%) after 12 h. The mode of cell death induced by cyanide is clearly apoptosis in CECs, as shown by Hoechst 33,342 staining and transmission electron microscope, i.e. cyanide induced condensation and margination of chromatin, nuclear fragmentation and shrinkage of cell body and condensed apoptotic bodies in CECs. Most importantly, we found that the tight junction between two CECs was disrupted 12 h after chemical-ischemia, i.e. when CECs underwent apoptosis, the tight junctional complexes became thinner and rough; the cleft of tight junction between two CECs became blurred and more wider, and membranes of tight junction were course and irregular; and the adherens junctions were damaged. These results indicate that chemical hypoxia-ischemia induces apoptotic cell death in CECs and alters the microvascular integrity by disrupting tight junction complexes, and suggest that CEC apoptotic death and disruption of tight junction may exacerbate ischemic insults to brain. Thus, prevention of CEC apoptotic death may contribute to improvements of ischemic insults.

Animals↗

PubMed2000

Identification of a novel ligand-receptor pair constitutively activated by ras oncogenes.

The Ras signaling pathway is thought to control the expression of a subset of yet to be defined genes that are crucial for cell growth and differentiation. Here we have identified by differential display a novel oncogenic Ras target, mob-5, encoding a 23-kDa cytokine-like secreted protein. Mob-5 expression could be induced by oncogenic Ha-ras and Ki-ras, but not by normal ras activation. Inhibitors of both Ha-Ras and mitogen-activated protein kinase kinase completely abolished the mob-5 expression in ras transformed cells, with concomitant loss of the transformation phenotype. Using an alkaline phosphatase-tagged Mob-5 as ligand, a putative Mob-5 receptor was identified on the cell surface of oncogenic ras transformed cells. Thus, the Mob-5/Mob-5 receptor may represent a novel putative autocrine loop coordinately activated by ras oncogenes.

Amino Acid Sequence↗

PubMed2000

Determining the growing season of land vegetation on the basis of plant phenology and satellite data in Northern China.

The objectives of this study are to explore the relationships between plant phenology and satellite-sensor-derived measures of greenness, and to advance a new procedure for determining the growing season of land vegetation at the regional scale. Three phenological stations were selected as sample sites to represent different climatic zones and vegetation types in northern China. The mixed data set consists of occurrence dates of all observed phenophases for 50-70 kinds of trees and shrubs from 1983 to 1988. Using these data, we calculated the cumulative frequency of phenophases in every 5-day period (pentad) throughout each year, and also drew the cumulative frequency distribution curve for all station-years, in order to reveal the typical seasonal characteristics of these plant communities. The growing season was set as the time interval between 5% and 95% of the phenological cumulative frequency. Average lengths of the growing season varied between 188 days in the northern, to 259 days in the southern part of the research region. The beginning and end dates of the surface growing season were then applied each year as time thresholds, to determine the corresponding 10-day peak greenness values from normalized difference vegetation index curves for 8-km2 pixels overlying the phenological stations. Our results show that, at the beginning of the growing season, the largest average greenness value occurs in the southern part, then in the northern, and finally the middle part of the research region. In contrast, at the end of the growing season, the largest average greenness value is measured in the northern part, next in the middle and lastly the southern part of the research region. In future studies, these derived NDVI thresholds can be applied to determine the growing season of similar plant communities at other sites, which lack surface phenological data.

China↗

PubMed2000

p53 accumulation due to down-regulation of ubiquitin: relevance for neuronal apoptosis.

The p53 tumor suppressor protein is a major regulator of cell growth arrest and apoptosis in response to DNA damage. Both p53 function and stability are tightly controlled by Mdm2, which binds to the p53 N-terminus and targets p53 for ubiquitin-mediated proteolysis. Previous studies suggest that adrenalectomy-induced neuronal apoptosis is p53-dependent. Here we demonstrate both nuclear accumulation and functional activation of p53 protein in apoptotic hippocampal neurons from adrenalectomized rats. Increased p53 expression occurred despite the accumulation of its negative regulator, Mdm2, and the formation of p53-Mdm2 complexes. The persistence of p53 expression was explained by a striking decrease in free ubiquitin in p53-positive neurons. The addition of exogenous ubiquitin to p53-Mdm2 complexes from apoptotic neurons restored p53 degradation. These findings demonstrate a novel mechanism of p53 stabilization mediated by decreased ubiquitin levels. Regulation of free ubiquitin may therefore be an effective way to modulate p53-dependent apoptosis in certain cell types.

Adrenalectomy↗

PubMed2000

Atomic force microscopy analysis of intermediates in cobalt hexammine-induced DNA condensation.

The packaging pathway of cobalt hexammine-induced DNA condensation on the surface of mica was examined by varying the concentration of Co(NH3)6(3+) in a dilute DNA solution and visualizing the condensates by atomic force microscopy (AFM). Images reveal that cobalt hexammine-induced DNA condensation on mica involves well-defined structures. At 30 microM Co(NH3)6(3+), prolate ellipsoid condensates composed of relatively shorter rods with linkages between them are formed. At 80 microM Co(NH3)6(3+), the condensed features include toroids with average diameter of approximately 240 nm as well as U-shaped and rod-like condensates with nodular appearances. The results imply that the condensates, whether toroids, U-shaped or rod-like structures have similar intermediate state which includes relatively shorter rod-like segments. The average size of the condensed toroids after incubated at room temperature for 5 h (approximately 240 nm) is much larger than that incubated for 0.5 h (approximately 100 nm). The results indicate that the condensation of DNA by Co(NH3)6(3+) is a kinetic-controlled process.

Adsorption↗

PubMed2000

Complete genomic sequence of 195 Kb of human DNA containing the gene GABRG2.

GABA (gamma-aminobutyric acid), as the main inhibitory neurotransmitter in the brain, plays an essential role for the overall balance between neuronal excitation and inhibition by acting on GABAA receptors, which are ligand-gated chloride channels. Impaired GABAergic function contributes to certain forms of epilepsy, schizophrenia, Alzheimer's Disease, and other neurological disorders. In order to identify possible genetic features and to further study biological regulation of GABAA receptor genes whose promoter elements and sequence anomalies may contribute to epileptic disorders, as an initial step, we shot-gun sequenced a BAC clone, dj082c10 (195,909-bp in size), encompassing human gamma(2) subunit of GABAA receptor (GABRG2). It is, we believe, the first genomic sequence of the GABA receptor gamma subunit family. Four contigs were assembled from 2950 reads prior to gap in an average redundancy of eight folds over the entire region. The precision of the consensus sequence was predicted to be 99.999% after closing gaps and finishing weak regions. The nine exons of GABRG2 spans an 85-kb region that had 81 SINEs comprising 22.32%, and nine L1 elements comprising 3.40%, respectively. However, the density of L1 in the regions flanking GABRG2 gene (29.45% by 45 elements) is significantly higher than that within the gene. The length of GABRG2 introns varies in the range of 1.5 kb to 38.1 kb.

Amino Acid Sequence↗

PubMed2000

[A preliminary study on the activation of superoxide dismutase by Tiopronin in patients with chronic hepatitis B].

OBJECTIVE: To observe the clearance effect of Tiopronin on oxygen free radicals in chronic hepatitis B patients. METHODS: The ranthine oxidase assay was used to detect superoxide dismutase (SOD) in 80 chronic hepatitis B patients, the ALT, TBil, TP and AIG ratio of the patients were also tested. The 80 chronic hepatitis B patients were divided into two groups, the control group was treated with routine liver protective and jaundice regressing drugs while the treated group was additionally administered with Tiopromin besides the routine treatment. RESULTS: In two groups of patients with similar ages and sexes, there showed no differences in levels of SOD, ALT, TBil, TP and ALB before treatment, as the SOD in treated group and control group were 106.57 (40.68 NU/ml and 105.18(44.59 NU/ml respectively, while the normal value for SOD in 16 normal persons was 165.9(23.36 NU/ml. After treatment, there were significant differences (P< 0.01) in SOD, ALT, TBil and ALB levels which showed SOD 187.93(35.24 NU/ml, ALT 38.41(22.22 U/L, TBil 23.15(12.46 micromol/L, ALB 43.28 (4.21 g/L in the treated group and SOD 157.96(47.29 NU/ml, ALT 68.52(34.19 U/L, TBil 30.38(21.80 micromol/L and ALB 40.36(5.19 g/L in the control group. CONCLUSIONS: There showed a good therapeutic effect of Tiopronin on the clearance of oxygen free radicals in chronic hepatitis B patients and also it can improve the liver function.

Adult↗

PubMed2000

[Effect of emodin on fibroblasts in lupus nephritis].

OBJECTIVE: To observe the effects of emodin on human fibroblasts in culture of kidney in patients with lupus nephritis (LN). METHODS: Fibroblasts were isolated from culture of kidney of LN patients, and the effect of emodin on 3H-TdR incorporated rate of fibroblasts was observed. The apoptosis and c-myc gene expression were detected in the same time by flow cytometry. RESULTS: Emodin could inhibit the proliferation of fibroblasts, and promote the programmed cell death through upregulate c-myc gene expression in human renal fibroblasts. CONCLUSION: Emodin can inhibit proliferation and promote apoptosis of fibroblasts, which may be important in ameliorate interstitial fibrosis, thus improving prognosis of LN.

Apoptosis↗

PubMed2000

[p16, p53 and c-erbB-2 gene expression in bladder carcinoma].

OBJECTIVE: To investigate the expression of p16, p53 and c-erbB-2 proteins in bladder carcinoma and to analyze their correlation with tumor grade, clinic stage and metastasis. METHODS: Immunohistochemical method was used to detect the p16, p53 and c-erbB-2 gene expressions in 75 cases of bladder carcinoma. RESULTS: Positive rates of p16, p53 and c-erbB-2 in 75 cases of bladder cancer were 41.3%, 44.0% and 40.0%, respectively. p16 and c-erbB-2 gene expressions were related to the tumor grade and clinic stage (P < 0.05); p53 and c-erbB-2 gene expressions were related to the clinic stage and metastasis (P < 0.01). Oncogenes and/or antioncogenes altered expressions were found in 77.3% cases of bladder carcinoma, and oncogenes and/or antioncogenes with multiple altered expressions were found in 53.3% cases. CONCLUSION: The analysis of multiple oncogene and/or antioncogene is more valuable than that of single oncogene and/or antioncogene. The altered expression of oncogene c-erbB-2 and antioncogenes p16 and p53 might play a promotive role in the tumorigenesis and development of bladder tumors.

Adult↗

PubMed1999

Effects of local anesthetics on phospholipase D activity in differentiated human promyelocytic leukemic HL60 cells.

Local anesthetics impair certain functions of neutrophils, and phospholipase D (PLD) is considered to play an important role in the regulation of these functions. To understand the mechanisms by which local anesthetics suppress the functions of neutrophils, we examined the effects of local anesthetics on PLD in neutrophil-like differentiated human promyelocytic leukemic HL60 cells. Tetracaine, a local anesthetic, inhibited formyl-methionyl-leucyl-phenylalanine (fMLP)- and 4beta-phorbol 12-myristate 13-acetate (PMA)-induced PLD activation, but potentiated fMLP-stimulated phospholipase C activity. All four local anesthetics tested suppressed PMA-induced PLD activation to different extents, and the order of their potency was tetracaine > bupivacaine > lidocaine > procaine. In a cell-free system, tetracaine suppressed guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)-induced PLD activation as well as PMA-induced PLD activation. Western blot analysis revealed that tetracaine prevented the membrane translocation of PLD-activating factors, ADP-ribosylation factor, RhoA, and protein kinase Calpha. Tetracaine also inhibited the activity of recombinant hPLD1a in vitro. These results suggest that local anesthetics suppress PLD activation in differentiated HL60 cells by preventing the membrane translocation of PLD-activating factors, and/or by directly inhibiting the enzyme per se. Therefore, it could be assumed that local anesthetics would suppress the functions of neutrophils by inhibition of PLD activation.

Anesthetics, Local↗

PubMed1999

Intramitotic and intraclonal variation in proliferative potential of human diploid cells: explained by telomere shortening.

Normal human diploid cells can only divide for a limited number of times (known as the Hayflick limit). They manifest two unique features during in vitro senescence. The division capability of individual cells in a clone, though all derived from a same ancestor, is heterogeneous with a distinct bimodal distribution. Two sister cells derived from a same parent cell can have a large difference in their doubling potentials. These two unique features have not been properly explained by any known physiological process since their observation in 1980. Here I represent a telomere-shortening model based on recent experimental measurement of telomere deletion in human cells. Using computer simulation, I show that the model satisfactorily explains the intraclonal and intramitotic variation in division capability of human diploid cells. Moreover, the simulations predict that human cells may only monitor the shortening of a few, most likely two, telomeres to regulate their proliferative potential.

Clone Cells↗

PubMed1999

Telomere shortening and the population size-dependency of life span of human cell culture: further implication for two proliferation-restricting telomeres.

Cultures of normal human cell can only undergo a finite number of population doublings. The proliferative life span of a culture is affected by population size, i.e., the number of cells a culture maintains. A 1000-fold transient reduction in population size can reduce the life span by as many as eight population doublings. The limited proliferative potential of human cells has been speculated to be a result of telomere shortening that occurs during DNA synthesis at each round of cell division. In this paper, I use computer simulation to test the telomere theory of cell aging against the population size-dependency of life span of human cell culture. It is found that telomere shortening well explains the above phenomenon. In addition, the results suggest that the proliferative potential of human cells might be limited by the shortening of only a few, most likely two, specific telomeres, providing further support to the same conclusion put forward in my previous paper (Tan, 1999).

Cell Division↗

PubMed1999

Local anesthetics inhibit muscarinic receptor-mediated activation of extracellular signal-regulated kinases in rat pheochromocytoma PC12 cells.

BACKGROUND: Because protein phosphorylation is a key mechanism for controlling cellular functions and extracellular signal-regulated kinase (ERK) plays a role in cellular signal transduction, the authors wanted to determine whether local anesthetics interfere with biochemical signaling molecules. METHODS: Protein tyrosine phosphorylation and ERK activation induced by carbachol, an agonist for muscarinic acetylcholine receptors, were examined in rat pheochromocytoma PC12 cells, a model for investigating signal transduction. Carbachol-induced tyrosine-phosphorylated proteins of 44 and 42 kd were determined by Western blot analysis and identified as activated ERK1 and ERK2 using anti-ERK antibody. The ERK activation was blocked by preincubation with atropine or an M3 muscarinic acetylcholine receptor antagonist 4-diphenyacetooxy-1, 1-dimethylpiperidinium, indicating that is was mediated by M3 muscarinic acetylcholine receptor activation. Then, in the presence of local anesthetic, the carbachol-induced tyrosine phosphorylation and ERK activation were evaluated. The effects of three Na+ current-modifying reagents on carbachol-induced ERK activation were also evaluated. RESULTS: Procaine (10(-4) to 10(-3) M) inhibited carbachol-induced tyrosine phosphorylation and ERK activation in a concentration-dependent manner. Although tetracaine, lidocaine, and bupivacaine similarly suppressed carbachol-induced tyrosine phosphorylation and ERK activation, neither tetrodotoxin, veratridine, nor ouabain affected the carbachol-induced ERKs activation. Both ERKs were also activated by 4beta-phorbol 12-myristate 13-acetate, an activator of protein kinase C, and fluoroaluminate (AlF4-), respectively, but procaine did not affect ERK activation induced by these two substances. The inhibition of carbachol-induced ERK activation by procaine was not modified by a phosphatase inhibitor, calyculin A. CONCLUSIONS: The current results indicate that local anesthetics inhibit the activity of the signal-transducing molecule(s) leading to M3 muscarinic acetylcholine receptor-mediated ERK activation in PC12 cells. Such action is unlikely to be a result of the drug's action on Na+ channels or on the electrochemical gradients of the neuronal cell membrane.

Anesthetics, Local↗

PubMed1999

Treatment of epigastralgia by external application of huweigao at shenque point.

140 cases of epigastralgia were divided into two groups at random. The 100 cases in the treatment group were treated with Huweigao externally applied at Shenque (Ren 8), and the 40 cases in the control group by oral administration of Weinaian capsule. After a one-month treatment, the total symptom-relieving rate and the gastroscopy-proved effective rate were 94.0% and 52.6% respectively in the treatment group, much superior to those in the control group.

Acupuncture Points↗

PubMed1998

Immunohistochemical localization of redox factor-1 (Ref-1) in Alzheimer's hippocampus.

Redox factor-1 (Ref-1) is a dual-function protein involved in both DNA repair and transcriptional regulation. Ref-1 is modulated by cerebral ischemia and other oxidative stressors, and also regulates the DNA-binding activities of transcription factors implicated in Alzheimer's disease (AD)-related neurodegeneration. The present study examined Ref-1 expression in the AD hippocampus by immunohistochemistry. Although Ref-1 immunostaining was relatively low in control brain sections, senile plaques and other plaque-like structures in the AD brain were Ref-1-positive. Cells with increased Ref-1 immunoreactivity were also observed in regions of neuronal injury. These results suggest that Ref-1 might contribute to senile plaque formation, and that overexpression of Ref-1 in injured neurons may be part of a response to oxidative stress and an attempt to repair damaged DNA in AD.

Aged↗

PubMed1998

Genetic engineering of proteins with cell membrane permeability.

The discovery of methods for generating proteins with inherent cell membrane-translocating activity will expand our ability to study and manipulate various intracellular processes in living systems. We report a method to engineer proteins with cell-membrane permeability. After a 12-amino acid residue membrane-translocating sequence (MTS) was fused to the C-terminus of glutathione S-transferase (GST), the resultant GST-MTS fusion proteins were efficiently imported into NIH 3T3 fibroblasts and other cells. To explore the applicability of this nondestructive import method to the study of intracellular processes, a 41-kDa GST-Grb2SH2-MTS fusion protein containing the Grb2 SH2 domain was tested for its effect on the epidermal growth factor (EGF)-stimulated signaling pathway. This fusion protein entered cells, formed a complex with phosphorylated EGF receptor (EGFR), and inhibited EGF-induced EGFR-Grb2 association and mitogen-activated protein kinase activation.

3T3 Cells↗