Biomedical subjects

Mei Zhang

Publications and source records attributed to Mei Zhang.

At least 145 records · Page 8Linked to original sources

PubMed2003

Decreased pigment epithelium-derived factor and increased vascular endothelial growth factor levels in pterygia.

PURPOSE: Pterygia are histologically composed of proliferating fibrovascular tissue. This study compared expression levels of an angiogenic inhibitor, pigment epithelium-derived factor (PEDF), in pterygia with those in normal corneal and conjunctival tissues. METHODS: The normal human conjunctival and corneal tissues were obtained from surgery or from donor eyes without ocular diseases. Pterygia were excised by therapeutic surgery under a microscope. Pigment epithelium-derived factor and vascular endothelial growth factor (VEGF) were measured by Western blot analysis. Their cellular localizations were determined by immunohistochemistry. RESULTS: Intensive PEDF immunostaining was detected in all the normal corneal and conjunctival samples analyzed, predominantly in the epithelium and endothelium of the cornea and in the epithelium of the limbus and conjunctiva. Under the same immunostaining conditions, pterygial samples showed negative or faint PEDF staining. In contrast, the same pterygial samples all showed intensive VEGF staining, predominantly in the epithelium and in blood vessels. Western blot analysis confirmed that the average PEDF level in pterygia was drastically lower than those in normal corneal and conjunctival tissues, respectively. In contrast, the VEGF level in pterygia was significantly higher than in the normal tissues. CONCLUSION: Pterygia exhibit significantly lower PEDF but higher VEGF levels than those in normal corneas and conjunctivae. The decreased PEDF level in pterygia may play a role in the formation and progression of pterygia.

Case-Control Studies↗

PubMed2003

Correlation of CYP2D6 genotype with perhexiline phenotypic metabolizer status.

Perhexiline is metabolized by CYP2D6 and has concentration-related hepatoxicity and peripheral neuropathy. The risk of toxicity is reduced using therapeutic drug monitoring. CYP2D6 genotyping before therapy may allow earlier appropriate dosing. This study aimed to determine whether assessment of CYP2D6 genotype in patients on perhexiline could predict accurately metabolizer status as determined by the perhexiline metabolic ratio (MR). Blood samples from patients stabilized on perhexiline were analysed for CYP2D6 genotype and for concentrations of perhexiline and its hydroxy metabolite. The MR was determined. Of 74 patients, five were poor metabolizers (PM) defined by a MR<0.4, and the remainder were extensive metabolizers (EM). The genotypes were: *1/*1 (n=21), *1/*4 (n=18), *1/*2 (n=12), *1/*3 (n=2), *1/*5 (n=1), *1/*9 (n=2), *1/*10 (n=2), *2/*4 (n=4), *2/*2 (n=3), *4/*41 (n=3), *2/*41 (n=1), *41/*41 (n=1), *4/*9 (n=1), *4/*5 (n=1), *5/*6 (n=1) and *4/*6 (n=1). Allele frequencies were consistent with those reported in population studies. The 3 PMs with the lowest MR were predicted by genotype (*4/*5, *5/*6, *4/*6). The other 2 PMs had intermediate metabolizer genotypes and were on CYP2D6 inhibiting drugs. Amongst the EMs, the highest MR was associated with *1 and *2 allele combinations and the MR was progressively lower with the presence of alleles with intermediate function (*9, *10, *41) followed by alleles with no functional product (*3, *4, *5, *6). Thus, a gene-dose effect was observed. Genotype predicted PM phenotype and also intermediate metabolizers. Determination of CYP2D6 genotype before therapy with perhexiline may help predict perhexiline dose requirements and reduce the risk of perhexiline concentration-related toxicity.

Adult↗

PubMed2003

Effects of mutant ubiquitin on ts1 retrovirus-mediated neuropathology.

ts1 is a temperature-sensitive mutant of Moloney murine leukemia virus that induces a rapid spongiform encephalopathy in mice infected as newborns. The pathological features include the formation of ubiquitinated inclusions resembling Lewy bodies. To determine how perturbation of the ubiquitin-proteasome pathway might affect ts1-mediated neurodegeneration, the virus was introduced into transgenic mice in which the assembly of ubiquitin chains was compromised by the expression of dominant-negative mutant ubiquitin. The onset of symptoms was greatly delayed in a transgenic mouse line expressing K48R mutant ubiquitin; no such delay was observed in mice expressing a wild-type ubiquitin transgene or K63R mutant ubiquitin. The extended latency was found to correlate with a delayed increase in viral titers. Pathological findings in K48R transgenic mice at 60 days were found to be similar to those in the other strains at 30 days, suggesting that while delayed, the neurodegenerative process in K48R mice was otherwise similar. These data demonstrate the sensitivity of retroviral replication to the partial disruption of ubiquitin-mediated proteolysis in vivo, a finding that may have therapeutic potential.

Animals↗

PubMed2003

Paracrine overexpression of IGFBP-4 in osteoblasts of transgenic mice decreases bone turnover and causes global growth retardation.

Insulin-like growth factor binding protein 4 (IGFBP-4) is abundantly expressed in bone and is generally believed to function as an inhibitor of IGF action. To investigate the function of locally produced IGFBP-4 in bone in vivo, we targeted expression of IGFBP-4 to osteoblasts using a human osteocalcin promoter to direct transgene expression. IGFBP-4 protein levels in calvaria of transgenic (OC-BP4) mice as measured by Western ligand blot were increased 25-fold over the endogenous level. Interestingly, levels of IGFBP-5 were decreased in the OC-BP4 mice, possibly because of a compensatory alteration in IGF-1 action. Morphometric measurements showed a decrease in femoral length and total bone volume in transgenic animals compared with the controls. Quantitative histomorphometry at the distal femur disclosed a striking reduction in bone turnover in the OC-BP4 mice. Osteoblast number/bone length and bone formation rate/bone surface in OC-BP4 mice were approximately one-half that seen in control mice. At birth, OC-BP4 mice were of normal size and weight but exhibited striking postnatal growth retardation. Organ allometry (mg/g body weight) analysis revealed that, whereas most organs exhibited a proportional reduction in weight, calvarial and femoral wet weights were disproportionally small (approximately 70% and 80% of control, respectively). In conclusion, paracrine overexpression of IGFBP-4 in the bone microenvironment markedly reduced cancellous bone formation and turnover and severely impaired overall postnatal skeletal and somatic growth. We attribute these effects to the sequestration of IGF-1 by IGFBP-4 and consequent impairment of IGF-1 action in skeletal tissue.

Animals↗

PubMed2003

[Clinical characteristics of patients with dry eye syndrome].

OBJECTIVE: To learn the clinical characteristics of patients with dry eye syndrome. METHODS: The following items were recorded in 115 patients (229 eyes) with dry eye, including symptoms, causation, systematic diseases, slit-lamp examination, tear break-up time, basal and reflex Schirmer's test, vital staining (fluorescent and rose bangle) and meibomian gland dysfunction examination. Rheumatoid factor and auto-antibody detection were performed in Sjögren's syndrome suspected patients. RESULTS: Aqueous tear deficiency (ATD, 48.7%) ranked the most common type, followed by over-evaporation dry eye (34.8%), mixed type (13.9%) and conjunctivochalasis (3.5%). In all the causes of the dry eye, about 11.3% had Sjögren syndrome (SS). Females suffering from dry eye were more than males, especially SS. Dryness was the most common symptom (84.0%), especially in ATD patients, then followed by ocular fatigue (72.0%), foreign body sensation (64.0%) and impairment of vision (56.0%). The ocular irritation was more severe in meibomain gland dysfunction (MGD) patients than in ATD patients. Among the results of tear break-up time (BUT), rose bangle (Rb) staining and fluorescent (Fl) staining in all types of dry eye, significant relationship was found among them, especially between Rb and Fl score (r = 0.612, P = 0.000). SS patients had much more severe abnormality in all the four signs than non-SS aqueous tear deficiency (NSTD) and MGD patients. However, in the comparisons of BUT, Rb and Fl between NSTD and MGD patients, there were no significant differences. CONCLUSION: Symptoms combined with examinations of BUT, Schirmer's test, Fl and Rb staining and meibomian gland function are the necessary means to diagnose most of the dry eye patients.

Adolescent↗

PubMed2003

Gene expression profile changes in NB4 cells induced by arsenic trioxide.

AIM: To investigate the gene expression profiles of acute promyelocytic leukemia (APL) cell line NB4 treated with arsenic trioxide (As2O3) using cDNA microarray. METHODS: Two cDNA probes were prepared through reverse transcription from mRNA of NB4 cells treated with or without arsenic trioxide. The probes were labeled with Cy3 and Cy5 fluorescence dyes individually, hybridized with cDNA microarray representing 1003 different human genes, and their fluorescent intensities were scanned. The genes were screened through the analysis of the difference in two gene expression profiles. RESULTS: The analysis of gene expression profiles indicated that after the treatment of arsenic trioxide (0.5 micromol/L) 3 genes were up-regulated, among which, PSMB6 gene was involved in proteasome degradation pathway, and 18 genes related to RNA processing, protein synthesis, and signal transduction were down-regulated. CONCLUSION: PSMB6 and ITGB1 genes may be related to the differentiation and/or apoptosis of NB4 cells induced by As2O3.

Antineoplastic Agents↗

PubMed2003

[Development of salivary gland tumors in pleomorphic adenoma gene 1 transgenic mice].

OBJECTIVE: Activation and overexpression of pleomorphic adenoma (PLAG1) gene due to t(3;8)(p21;q12) translocation are associated with the development of human pleomorphic adenomas of the salivary glands. This study was conducted to generate ubiquitously-expressed or tissue-specific expressed PLAG1 transgenic mice and to elucidate the role of PLAG1 gene in tumorigenesis in vivo. METHODS: Human PLAG1 cDNA was cloned from salivary gland tumor or placenta tissues by RT-PCR. Ubiquitous expression vector pCMV-EGFP/PLAG1 driven by CMV promoter and tissue-specific expression vector pMMTV-PLAG1 driven by MMTV LTR were constructed. NIH3T3 cells transiently transfected with pCMV-EGFP/PLAG1 showed high expression of PLAG1 in nucleus. Transgenes were microinjected into pronucleus of zygotes to generate transgenic mice. RESULTS: It was found that the human PLAG1 cDNA cloned from several salivary gland tumor and normal placenta tissues consistently showed a variation of a single nucleotide at the same position when compared with the human PLAG1 cDNA sequence in Genbank (Accession No. U65002), which led to T458P at protein level. It might be a single nucleotide polymorphism (SNP)locus. Fused EGFP/PLAG1 protein was found to be localized in the nucleus of NIH3T3 cells transiently transfected with pCMV-EGFP/ PLAG1. Several pCMV-EGFP/PLAG1 and pMMTV-PLAG1 transgenic mouse lines were obtained respectively. As might be expected, pMMTV-PLAG1 transgenic mice spontaneously developed salivary gland tumors in three independent lines, among which, line 42 showed tumorigenic phenotype in 100% of transgenic mice within three months after birth. CONCLUSION: Overexpression of PLAG1 gene plays a crucial role in tumorigenesis of salivary gland tumors.

Animals↗

PubMed2003

Effect of spleen on immune function of rats with liver cancer complicated by liver cirrhosis.

OBJECTIVE: To establish a rat model of liver cancer complicated by liver cirrhosis and explore the effects of the spleen on immune function in this model. METHODS: Liver cirrhosis was inflicted in rats by percutaneous injection of 40% CCl4 on the back. Walker-256 tumor cells were inoculated in the cirrhotic liver and splenectomy was performed. Two weeks later, the growth and metastasis of tumor were observed and the amount of ascites and the activity of NK cells and CD25 cells were investigated. RESULTS: The amount of ascites and tumor volume were significantly higher in splenectomy group than in controls (P<0.01). Two weeks after inoculation, the activity of NK cells in both groups was decreased as compared with that before the inoculation (P<0.01). There was no significant difference between the two groups before and after the inoculation (P>0.05). The number of CD25 in both groups was higher than that before the inoculation (P<0.01). However, there was no significant difference between the two groups before and after the inoculation (P>0.05). CONCLUSIONS: Splenectomy in early stage of tumor inoculation can stimulate the tumor growth and metastasis. The activity of NK cells and the number of CD25 are inhibited by tumor itself, not by splenectomy.

Animals↗

PubMed2003

[Clinical observation on treatment of aplastic anemia patients by zaizhang decoction combined with Western medicine].

OBJECTIVE: To study the effect of Composite Zaizhang decoction (ZZD) on immune function of chronic aplastic anemia (CAA) patients. METHODS: To determine the levels of T-lymphocyte subset, serum tumor necrosis factor (TNF-alpha) and interleukin-2 (IL-2) in CAA patients before and after treatment, and to analyse the regulation of their changes comparatively with the group treated with conventional treatment and a normal control group. RESULTS: Before treatment, CD4 was lower, CD8 higher, CD4/CD8 ratio also lower, TNF-alpha and IL-2 were higher in the ZZD treated group than those in the normal control group, with significant difference (P < 0.05), but after ZZD treatment, these indexes were all inversely changed, as compared with those before treatment and with those in the control group, the difference was significant (P < 0.05). CONCLUSION: ZZD might relieve the hemopoietic inhibition so as to promote the recovery of hemopoietic function through improving the T-lymphocyte subset and reducing the release of hemopoietic negative ragulatory factors such as TNF-alpha and IL-2 etc.

Adolescent↗

PubMed2003

[Research advances on function of promyelocytic leukemia (PML) protein].

Through reviewing research advances on promyelocytic leukemia(PML) protein at home and abroad in recent years, the authors summarized the biological functions of PML protein in this paper. Recent researches indicated that all PML protein isoforms have RBCC (Ring finger domain, B-box, Coiled-Coil domain, RBCC)or TRIM (TRIpartite motif). There was a close relationship between the three SUMO-1 (small ubiquitin-related modifier, SUMO-1) modification site of PML protein and its location in nuclear bodies (NBs). Moreover, the location of PML protein in NBs is very important for the exertion of the function of PML protein and the formation of NBs. PML protein possesses multiple biological functions, such as intrinsic antiviral activities, suppressing the growth of tumor, participating in the differentiation of hemopoietic progenitor, regulating transcription of genes, inducing cell apoptosis, and so on. The PML gene haploinsufficiency and the formation of PML-RARalpha fusion protein are not only the pathogenesis of APL but also the target of treatment.

Animals↗

PubMed2003

[Confocal microscopy in transplanted human corneas].

PURPOSE: The aim of the study was in-real time observation and morphological evaluation of the transplanted human corneas, using confocal 2.0 microscopy. METHODS: Twelve eyes of 12 patients on 3-7 days after lamellar keratoplasty (LKP), 8 eyes of 8 patients at 1 year after LKP, and 10 eyes of 10 patients at 3-7 days after penetrating keratoplasty (PKP), 11 eyes of 11 patients at 1 year after PKP were examined by confocal 2.0 microscopy in vivo. Images were recorded by continuously focusing the optical section through the full thickness central cornea. RESULTS: 3-7 days after LKP, small stromal cells, cranny-like dark strias and nerves were seen in transplanted corneas. There were highly reflective regions and dots in the lamellar interface. One year after LKP, the nerves disappeared. There were less highly reflective regions, but the dots still can be seen. Some gross dark strias were seen in the posterior stroma and the density of the endothelium cells was normal. 3-7 days after PKP, keratocytes were activated. Nerves and gross dark strias could be seen in transplanted corneas. The density of the endothelium cells was normal, with some highly reflective dots deposited among them. One year after PKP, the nerves disappeared, and strias still existed. The density of the endothelium cells decreased significantly. CONCLUSIONS: Confocal scanning microscopy is a new tool for the study of cellular morphology and construction of transplanted human corneas. It can be used in the evaluation of operation effect, clinical observation and follow-up.

Adult↗

PubMed2003

[Effect of danshen injection on expression of platelet membrane glycoproteins in patients with type II diabetes mellitus].

OBJECTIVE: To investigate the effect of Danshen Injection on platelet membrane glycoprotein expression and fibrinogen binding in patients with type II diabetes mellitus (DM). METHODS: 82 patients and 30 normal individuals were enrolled into this study. Platelet glycoprotein (GP) Ib, Gp IIb, GP IIIa, GP IIb-IIIa complex and p-selectin expression as well as fibrinogen binding were analyzed by flowcytomery. RESULTS: The platelet membrane GP IIb-IIIa complex, p-selectin expression and fibrinogen binding were higher in patients with vascular diseases than those of normal subjects and the patients without vascular diseases. Platelet surface GP Ib expression in patients with vascular diseases was lower than the other two groups. On the other hand, the GP IIb and GP IIIa were not significantly changed. There was no difference between the patients without vascular disease and the normal. Danshen Injection may improve above-mentioned the marks. CONCLUSION: Dan Shen Injection may reduce the activity of platelet membrane glycoproteins and improve the vascular disease.

Adult↗

PubMed2003

[Cardioprotective effect and influence on NOS expression of Montelukast sodium in rats].

AIM: To determine the protective effect and influence on NOS expression of Montelukast sodium--a leukotriene antagonist on myocardial necrosis in rats. METHODS: Myocardial ischemia and necrosis were induced in rats by isoproterenol (2 mg.kg-1, s.c., qd for 2 d). Serum activity of LDH, CK, MDA, NO content in myocardium and scope of myocardial necrosis were measured. nNOS, iNOS and eNOS were investigated by immunohistochemical evaluation. RESULTS: Decreased serum level of LDH, CK, MDA and attenuated myocardial necrosis area were found in rats pretreated with Montelukast sodium 10 and 30 mg.kg-1. Montelukast sodium 30 mg.kg-1 also enhanced NO content in myocardium. Montelukast sodium activated the eNOS expression and reduced the iNOS expression. CONCLUSION: Montelukast sodium is cardioprotective during myocardial injury in rats by halting the leukotrienes-induced inflammatory response and upregulating the eNOS expression as well as downregulating the iNOS expression. This may represent an approach to the treatment of myocardial ischemia with leukotriene antagonists.

Acetates↗

PubMed2003

[Effect of resveratrol alone and its combination with cyclosporin A on the immune function of human peripheral blood T lymphocytes].

AIM: To investigate the effect of resveratrol (Res) alone and its combination with cyclosporin A (CsA) on the proliferation of human peripheral blood T lymphocytes (hPBTCs), transformation into lymphoblasts, as well as IL-2 and INF-gamma production. METHODS: The proliferation of hPBTCs was detected by MTT colorimetry. The lymphocyte transformation rate was examined by morphologic method. The levels of IL-2 and INF-gamma in lymphocyte culture supernatant were detected by ELISA. RESULTS: When the concentration of resveratrol was over 2.5 mg/L, especially 10 mg/L, the proliferation and transformation rate of hPBTCs decreased significantly (P<0.05). The levels of IL-2 and INF-gamma in lymphocyte culture supernatant reduced markedly (P<0.05), on condition that the concentration of resveratrol was over 5 mg/L. The combination of more than 2.5 mg/L of resveratrol with cyclosporine A had synergism. CONCLUSION: Resveratrol can suppress notably the proliferation and transformation of human lymphocytes and the combination of resveratrol at a given concentration with cyclosporine A can enhance immune suppression.

Cyclosporine↗

PubMed2002

Highly coordinated gene regulation in mouse skeletal muscle regeneration.

Mammalian skeletal muscles are capable of regeneration after injury. Quiescent satellite cells are activated to reenter the cell cycle and to differentiate for repair, recapitulating features of myogenesis during embryonic development. To understand better the molecular mechanism involved in this process in vivo, we employed high density cDNA microarrays for gene expression profiling in mouse tibialis anterior muscles after a cardiotoxin injection. Among 16,267 gene elements surveyed, 3,532 elements showed at least a 2.5-fold change at one or more time points during a 14-day time course. Hierarchical cluster analysis and semiquantitative reverse transcription-PCR showed induction of genes important for cell cycle control and DNA replication during the early phase of muscle regeneration. Subsequently, genes for myogenic regulatory factors, a group of imprinted genes and genes with functions to inhibit cell cycle progression and promote myogenic differentiation, were induced when myogenic stem cells started to differentiate. Induction of a majority of these genes, including E2f1 and E2f2, was abolished in muscles lacking satellite cell activity after gamma radiation. Regeneration was severely compromised in E2f1 null mice but not affected in E2f2 null mice. This study identifies novel genes potentially important for muscle regeneration and reveals highly coordinated myogenic cell proliferation and differentiation programs in adult skeletal muscle regeneration in vivo.

Animals↗

PubMed2002

Gluing the respiratory chain together. Cardiolipin is required for supercomplex formation in the inner mitochondrial membrane.

Cytochrome bc(1) complex (complex III) and cytochrome c oxidase complex (complex IV) are multisubunit homodimers that are essential components of the mitochondrial respiratory chain. Complexes III and IV associate to form a supercomplex that can be displayed using blue native polyacrylamide gel electrophoresis. Both homodimeric complexes contain tightly associated cardiolipin (CL) required for function. We report here that in a crd1Delta strain of yeast (null in expression of CL synthase) approximately 90% of complexes III and IV were observed as individual homodimers; only the supercomplex was observed with CRD1 wild type cells. Introduction of a plasmid born copy of the CRD1 gene under exogenous regulation by doxycycline made possible controlled variation in the in vivo CL levels. At an intermediate level of CL, a mixture of individual homodimers (30%) and supercomplex (70%) was observed. These results strongly indicate that CL plays a central role in higher order organization of components of the respiratory chain of mitochondria.

Anti-Bacterial Agents↗

PubMed2002

Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization.

To examine the local actions of IGF signaling in skeletal tissue in a physiological context, we have used Cre-mediated recombination to disrupt selectively in mouse osteoblasts the gene encoding the type 1 IGF receptor (Igf1r). Mice carrying this bone-specific mutation were of normal size and weight but, in comparison with normal siblings, demonstrated a striking decrease in cancellous bone volume, connectivity, and trabecular number, and an increase in trabecular spacing. These abnormalities correlated with a striking decrease in the rate of mineralization of osteoid that occurred despite an unexpected osteoblast and osteoclast hyperactivity, detected from the significant increments in both osteoblast and erosion surfaces. Our findings indicate that IGF1 is essential for coupling matrix biosynthesis to sustained mineralization. This action is likely to be particularly important during the pubertal growth spurt when rapid bone formation and consolidation are required.

Animals↗

PubMed2002

MLN64 mediates mobilization of lysosomal cholesterol to steroidogenic mitochondria.

This study demonstrates that the steroidogenic acute regulatory protein-related lipid transfer (START) domain-containing protein, MLN64, participates in intracellular cholesterol trafficking. Analysis of the intracellular itinerary of MLN64 and MLN64 mutants tagged with green fluorescent protein showed that the N-terminal transmembrane domains mediate endocytosis of MLN64 from the plasma membrane to late endocytic compartments. MLN64 constitutively traffics via dynamic NPC1-containing late endosomal tubules in normal cells; this dynamic movement was inhibited in cholesterol-loaded cells, and MLN64 is trapped at the periphery of cholesterol-laden lysosomes. The MLN64 START domain stimulated free cholesterol transfer from donor to acceptor mitochondrial membranes and enhanced steroidogenesis by placental mitochondria. Expression of a truncated form of MLN64 (DeltaSTART-MLN64), which contains N-terminal transmembrane domains but lacks the START domain, caused free cholesterol accumulation in lysosomes and inhibited late endocytic dynamics. The DeltaSTART-MLN64 dominant negative protein was located at the surface of the cholesterol-laden lysosomes. This dominant negative mutant suppressed steroidogenesis in COS cells expressing the mitochondrial cholesterol side chain cleavage system. We conclude that MLN64 participates in mobilization and utilization of lysosomal cholesterol by virtue of the START domain's role in cholesterol transport.

Animals↗