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Biomedical subjects

X Meng

Publications and source records attributed to X Meng.

At least 145 records · Page 8Linked to original sources
PubMed1998

Myocardial gene reprogramming associated with a cardiac cross-resistant state induced by LPS preconditioning.

Lipopolysaccharide (LPS) preconditioning induces cardiac resistance to subsequent LPS or ischemia. This study tested the hypothesis that resistance to LPS and resistance to ischemia are two manifestations of cardiac cross-resistance which may involve reprogramming of cardiac gene expression. Rats were preconditioned with a single dose of LPS (0.5 mg/kg ip). Cardiac resistance to LPS was examined with a subsequent LPS challenge. Cardiac resistance to ischemia was determined by subjecting hearts to ischemia-reperfusion. Total RNA was extracted from myocardium for Northern analysis of mRNAs encoding protooncoproteins, antioxidant enzymes, and contractile protein isoforms. Rats preconditioned with LPS 1-7 days earlier acquired cardiac resistance to endotoxemic depression. This resistance temporally correlated with resistance to ischemia. Pretreatment with cycloheximide (0.5 mg/kg ip) abolished resistance to both LPS and ischemia. LPS preconditioning induced the expression of c-jun and c-fos mRNAs. LPS also transiently increased mRNAs encoding catalase and Mn-containing superoxide dismutase. The expression of both alpha- and beta-myosin heavy chain mRNAs was upregulated, whereas the expression of cardiac alpha-actin mRNA was suppressed. We conclude that 1) LPS induces sustained cardiac resistance to both LPS and ischemia, 2) resistance to ischemia and resistance to LPS seem to be two mechanistically indistinct components of cardiac cross-resistance, and 3) the cardiac cross-resistance is associated with reprogramming of myocardial gene expression.

Analysis of Variance↗
PubMed1998

Increased levels of myocardial IkappaB-alpha protein promote tolerance to endotoxin.

Endotoxin [lipopolysaccharide (LPS)] causes tumor necrosis factor-alpha (TNF-alpha)-mediated myocardial contractile depression. Tolerance to the cardiac toxicity of LPS can be induced by a prior exposure to LPS or by pretreatment with glucocorticoids. The mechanisms by which the myocardium acquires tolerance to LPS remain unknown. LPS causes phosphorylation and degradation of inhibitory kappaB-alpha (IkappaB-alpha), releasing nuclear factor-kappaB (NF-kappaB) to activate TNF-alpha gene transcription. We hypothesized that LPS induces supranormal synthesis of myocardial IkappaB-alpha protein and thus renders the myocardium tolerant to subsequent LPS. Rats were challenged with LPS after pretreatment with LPS, dexamethasone, or saline. In saline-pretreated rats, LPS caused a rapid decrease in myocardial IkappaB-alpha protein levels, activation of NF-kappaB, and increased TNF-alpha production. These events were followed by myocardial contractile depression. After the initial decrease in myocardial IkappaB-alpha, IkappaB-alpha protein levels rebounded to a level greater than control levels by 24 h. Dexamethasone pretreatment similarly increased myocardial IkappaB-alpha protein levels. In rats pretreated with either LPS or dexamethasone, myocardial IkappaB-alpha protein levels remained similar to control levels after LPS challenge. The preserved level of myocardial IkappaB-alpha protein was associated with diminished NF-kappaB activation, attenuated myocardial TNF-alpha production, and improved cardiac contractility. We conclude that LPS and dexamethasone upregulate myocardial IkappaB-alpha protein expression and that an increased level of myocardial IkappaB-alpha protein may promote cardiac tolerance to LPS by inhibition of NF-kappaB intranuclear translocation and myocardial TNF-alpha production.

Animals↗
PubMed1998

TNF-alpha and myocardial depression in endotoxemic rats: temporal discordance of an obligatory relationship.

Exogenous tumor necrosis factor-alpha (TNF-alpha) induces delayed myocardial depression in vivo but promotes rapid myocardial depression in vitro. The temporal relationship between endogenous TNF-alpha and endotoxemic myocardial depression is unclear, and the role of TNF-alpha in this myocardial disorder remains controversial. Using a rat model of endotoxemia not complicated by shock, we sought to determine 1) the temporal relationship of changes in circulating and myocardial TNF-alpha with myocardial depression, 2) the influences of protein synthesis inhibition or immunosuppression on TNF-alpha production and myocardial depression, and 3) the influence of neutralization of TNF-alpha on myocardial depression. Rats were treated with lipopolysaccharide (LPS, 0.5 mg/kg ip). Circulating and myocardial TNF-alpha increased at 1 and 2 h, whereas myocardial contractility was depressed at 4 and 6 h. Pretreatment with cycloheximide or dexamethasone abolished the increase in circulating and myocardial TNF-alpha and preserved myocardial contractile function. Similarly, treatment with TNF binding protein immediately after LPS prevented myocardial depression. We conclude that endogenous TNF-alpha mediates delayed myocardial depression in endotoxemic rats and that inhibition of TNF-alpha production or neutralization of TNF-alpha preserves myocardial contractile function in endotoxemia.

Analysis of Variance↗
PubMed1998

Extracellular matrix modulates macrophage functions characteristic to atheroma: collagen type I enhances acquisition of resident macrophage traits by human peripheral blood monocytes in vitro.

Activated resident macrophages sustain atheroma, and a high macrophage content is associated with plaque vulnerability. Factors leading to differentiation and activation of these blood-derived cells remain largely uncharacterized. We investigated the contribution of interaction with collagen type I, the predominant component of atherosclerotic matrix, to differentiation and modulation of characteristic macrophage functions, including intracellular lipid accumulation and production of the typical matrix-degrading enzyme matrix metalloproteinase (MMP)-9. When used as an adhesion substrate for human peripheral blood monocytes in vitro, collagen type I increased monocyte differentiation, assessed by analysis of CD71 expression and cell spreading. Culturing on collagen type I doubled the number of differentiated monocytes at 24 hours (44.9+/-1.4% versus 18.4+/-1.7% on uncoated dishes, P<.001, n=3 independent experiments) and was a stronger stimulus for differentiation than phorbol myristate acetate, a known inducer of monocyte differentiation. The effect of substrate on intracellular accumulation of modified lipoproteins was assessed by quantitative confocal microscopy of monocytes incubated with fluorescent acetylated LDL. The collagen type I substrate also doubled the number of macrophages containing intracellular lipid and significantly increased the individual intracellular loading. Monocytes cultured on collagen type I also released more MMP-9 than did cells plated directly on plastic. The role of monocyte spreading was further assessed by treatment with colchicine, an inhibitor of cytoskeletal function, or with genistein, a nonspecific inhibitor of tyrosine kinases, shown to participate in cell adhesion. Cell spreading was inhibited in 72.3+/-6.7% of colchicine-treated and in 62.4+/-6.4% of genistein-treated monocytes (n=3, P<.01 in both cases). The same conditions also decreased secretion of MMP-9, and genistein reduced the number of acetylated LDL-containing cells (from 286+/-7 to 184+/-8 cells/mm2 with genistein, n=3, P<.001). Data showed a strong correlation (r>.98) between monocyte spreading on collagen type I and intracellular lipid accumulation. Our results indicate that interaction with vascular matrix may play an important role in differentiation of peripheral blood monocytes into resident lipid-laden macrophages, which act as central stimulators throughout the natural history of atheroma.

Arteriosclerosis↗
PubMed1998

Interaction and dissociation by ligands of estrogen receptor and Hsp90: the antiestrogen RU 58668 induces a protein synthesis-dependent clustering of the receptor in the cytoplasm.

The in vivo interaction of estrogen receptor (ER) and Hsp90, demonstrated in the absence of hormone by a nuclear cotranslocation assay of the cytoplasmic Hsp90 with the karyophilic receptor, was disrupted by agonist and antagonist ligands, which, after dissociating the Hsp90, allowed the chaperone protein to be relocalized in the cytoplasm. The pure antiestrogen RU 58668 (RU), which was unable to stimulate an estrogen-dependent reporter gene and completely inhibited its estradiol-induced activity, also profoundly modified the subcellular distribution of ER in a specific time- and dose-dependent manner; ER appeared as speckled fluorescent clusters mainly located in the perinuclear region of the cytoplasm. The kinetics of appearance and reversal of the RU-dependent ER mislocalization in the presence or absence of cycloheximide demonstrated 1) that this effect was reversed by RU withdrawal or estradiol (E2) treatment, and 2) that cycloheximide with RU inhibited and reversed the ER cytoplasmic mislocalization induced by RU alone. These results point to a protein synthesis-dependent step in the mechanism of action of this antiestrogen. After RU treatment, a large portion of ER was found in the particulate fraction of the cytoplasm. However, confocal and electron microscopic analysis showed that ER clusters were not associated with specific cytoplasmic organelles or compartments. Using ER mutants, it was found that the ligand binding domain was sufficient for RU to produce receptor mislocalization, while the constitutive nuclear localization signals were dispensable. We propose that the antiestrogenic properties of RU are primarily due to the induction of an aggregation-prone receptor conformation that cannot undertake the constitutive and the ligand-induced nuclear localization function of the receptor because it is sequestered in the cytoplasm by fast turning over protein(s). We predict that antiestrogens able to block ER nuclear localization will behave as pure antihormones and will inhibit all the nuclear action of ER elicited by agonistic ligands or by ligand-independent mechanisms such as growth factor stimulation.

Animals↗
PubMed1998

[Correlation of interleukin 1 beta-converting enzyme(ICE) gene expression with gut epithelial cell apoptosis in septic mice].

OBJECTIVE: To investigate the correlation of gut epithelial cell apoptosis with ICE, IL1 beta gene expression in septic mice. METHODS: Sepsis was induced in mice by cecal ligation and puncture(CLP). Sham-operation group underwent the same manipulation but without CLP. 1, 3, 6 hours after CLP, gut epithelial cells, were isolated. IL1 beta, ICE gene expression was detected quantitatively by RT-PCR. Epithelial cell apoptosis was assessed by flow cytometric method and biochemically by DNA electrophoresis. RESULTS: The survival rate of CLP mice was 1/10 as compared to 10/10 of sham-operation mice. IL1 beta, ICE mRNA expression in CLP mice was significantly higher than that in the sham-operation group(P < 0.01); IL1 beta mRNA expression was parallel to ICE mRNA expression. The number of epithelial cell apoptosis was correlated excellently to the level of ICE, IL1 beta mRNA expression. Epithelial cell apoptosis could not be detected in sham-operation group at the indicated time points. CONCLUSION: ICE, IL1 beta gene overexpression may be involved in the vulnerability of epithelial cell apoptosis in septic mice.

Animals↗
PubMed1998

[Experimental study on mice scheduled-bone marrow transplantation].

OBJECTIVE: To enhance the grafting efficiency of bone marrow transplantation. METHODS: Lethally irradiated recipient Kunming mice were transplanted with bone marrow cells from normal Kunming mice either in one large (10(7)) number (BMT group) or in four separate small (10(5)-10(6)) numbers (scheduled BMT group) and the survival rate, hematopoiesis reconstitution and acute graft versus host disease (aGVHD) were compared between the two groups. RESULTS: Both BMT and SBMT (10(5) x 4) groups obtained the same survival rate of 30%. In SBMT (10(6) x 4) group, the peripheral WBC count, bone marrow nucleated cells and CFU-E, CFU-GM, CFU-S and CFU-F yields all returned to normal 17 days after irradiation. The degree of GVHD in SBMT group was less severe than that in BMT group, and the survival rate (60%) was significantly higher than that in BMT group (30%). CONCLUSION: SBMT can significantly enhance the grafting efficiency.

Animals↗
PubMed1998

[Ultrasound bone measurement of the tibia: comparison with vertebral dual-energy X-ray absorptiometry and appendicular single photon absorptiometry].

OBJECTIVE: Ultrasonic techniques have been used to assess the mechanical properties of bone. Recently, a new ultrasonic bone instrument, which measured the SOS (speed of sound) at the tibial shaft, has been introduced (Sound Scan 2000, Myriad Ultrasound Systems Ltd.). The aim of this work was to investigate the correlation of tibial SOS with bone mineral density (BMD). METHODS: The tibial SOS was measured in 213 healthy women (aged 22-83 years) and 56 female primary osteoporosis with vertebral fractures (aged 53-82 years). Values of SOS were compared with BMD assessed by dual energy x-ray absorptiometry (DEXA) at spine and hip sites and single photon absorptiometry (SPA) at the distal forearm. RESULTS: Tibial SOS correlated more closely with the BMD of lumbar, hip and forearm (r = 0.387-0.928, P < 0.001). The tibia SOS values and the BMD values measured by the DEXA and SPA were negatively correlated to age and years since menopause. In particular, they were obviously lower in the group of 50 years old. The tibial SOS of vertebral fracture group was significantly lower than that of well-matched non-fracture-group (n = 104, aged 51-84 years). CONCLUSIONS: Tibial SOS was significantly correlated with BMD measured by DEXA or SPA respectively and able to discriminate patients with vertebral fracture from the age-matched controls.

Absorptiometry, Photon↗
PubMed1998

[An antimicrobial experimental study on the traditional drug Anuqitabiao used by the Yi minority nationality].

The result of experimental study on the antimicrobial effect in vitro of the decoction, water-soluble ingredients and liposoluble ingredients of Anuqitabiao shows that decoction and water-soluble ingredients have certain inhibitory effect on all the tested bacteria, while the liposoluble ingredients do not, indicating the antimicrobial ingredients to be water-soluble. The result of antimicrobial experiment in vivo shows that neither different concentrations nor different separated parts of the decoction have any obvious protective effect on the pneumonococci-infected or staphylococciaureus-infected mice.

Animals↗
PubMed1998

[Inferior pulmonary ligament spindle-shaped covering on the anastomotic orifice in the surgery of cardiac carcinoma: experience in 772 patients with no anastomotic leakage or stricture successively].

OBJECTIVE: To prevent anastomotic leakage and stricture after the resection of cardiac carcinoma. METHODS: Since complications are the main causes of postoperative death and poor living quality, we modified anastomotic method, and projected anastomotic orifice to be covered with inferior pulmonary ligament(IPL) in spindle shape. RESULTS: From March 1987 to December 1996, 772 cases of cardiac carcinoma underwent surgical treatment with this method and no anastomotic leakage and stricture developed. CONCLUSION: The IPL has strong ability to adhere and heal. Anastomotic orifice is covered tightly and safely. No forth row 13 needed in not introsed anastomotic orifice, thus preventing stricture, because of lung expanding, IPL adheres to anastomotic orifice tightly, making stump space disappeared. IPL possesses well tenacity and can be used easily.

Adult↗
PubMed1998

[Comparative study of portal-systemic shunt rate measured by formula and radioactive method].

OBJECTIVE: To establish a new simple and useful formula for the observation of portosystemic shunt. METHOD: In the same animals and the same patients, portosystemic shunt rate was measured individually by the two different methods, i.e. formula and radio active method. Using the results of the radio active method as a gold standard, the reliability of the formula method was assessed tested. RESULT: In 11 normal dogs, the portal-systemic shunt rate measured by the formula and radio active methods was 7.03% and 7.55% respectively (P > 0.05). In 9 portosystemic shunting model dogs, the portosystemic shunt rate calculated from the two methods was 48.64% and 51.11% respectively (P > 0.05). In 22 patients with portal hypertension, the preoperative results from the formula and radioactive methods were 52.38% and 55.86% respectively (P > 0.05). In these patients, the postoperative portal-systemic shunt rate was 26.22% and 31.00% respectively (P > 0.05). CONCLUSION: These results fully testified the reliability of the formula method we had established.

Adult↗
PubMed1998

Interleukin-10 stabilizes inhibitory kappaB-alpha in human monocytes.

Interleukin-10 (IL-10) protects animals from lethal endotoxemia. This beneficial effect is mediated, in part, by inhibition of inflammatory cytokine production, including tumor necrosis factor-alpha (TNF-alpha). Evidence suggests that IL-10 may inhibit activation of the transcription factor nuclear factor-kappaB (NF-kappaB) through an unknown mechanism. NF-kappaB activation in response to inflammatory signals is dependent upon degradation of its associated inhibitory peptide, inhibitory kappaB-alpha (IkappaB-alpha). We hypothesized that IL-10 prevents human monocyte NF-kappaB activation and resultant TNF-alpha production by stabilization of IkappaB-alpha. The purpose of this study was to determine the effect of IL-10 on lipopolysaccharide (LPS)-induced human monocyte TNF-alpha production, NF-kappaB activation, and IkappaB-alpha degradation. Monocytes were isolated from human donors. Cells were stimulated with endotoxin (LPS, 100 ng/mL) with and without human IL-10 (10 ng/mL). Following stimulation, TNF-alpha was measured in cell supernatants by ELISA, NF-kappaB activity by electrophoretic mobility shift assay, and IkappaB-alpha levels by Western blot. We observed that after LPS stimulation of human monocytes, TNF-alpha increased to 798+/-67 pg/mL (p < .001 versus control). IL-10 attenuated LPS-stimulated TNF-alpha production (297+/-54; p < .001 versus LPS alone). After LPS stimulation in human monocytes, IkappaB-alpha protein levels decreased, and NF-kappaB DNA binding increased. IL-10 pretreatment prevented LPS-induced decreases in IkappaB-alpha protein levels and attenuated NF-kappaB DNA binding. IL-10 appears to prevent activation of NF-kappaB by preserving IkappaB-alpha protein levels, leading to a reduction in TNF-alpha release.

Animals↗
PubMed1997

Mating type switching in yeast controlled by asymmetric localization of ASH1 mRNA.

Cell divisions that produce progeny differing in their patterns of gene expression are key to the development of multicellular organisms. In the budding yeast Saccharomyces cerevisiae, mother cells but not daughter cells can switch mating type because they selectively express the HO endonuclease gene. This asymmetry is due to the preferential accumulation of an unstable transcriptional repressor protein, Ash1p, in daughter cell nuclei. Here it is shown that ASH1 messenger RNA (mRNA) preferentially accumulates in daughter cells by a process that is dependent on actin and myosin. A cis-acting element in the 3'-untranslated region of ASH1 mRNA is sufficient to localize a chimeric RNA to daughter cells. These results suggest that localization of mRNA may have been an early property of the eukaryotic lineage.

Actins↗
PubMed1997

Hyperplasia of lymphatic vessels in VEGF-C transgenic mice.

No growth factors specific for the lymphatic vascular system have yet been described. Vascular endothelial growth factor (VEGF) regulates vascular permeability and angiogenesis, but does not promote lymphangiogenesis. Overexpression of VEGF-C, a ligand of the VEGF receptors VEGFR-3 and VEGFR-2, in the skin of transgenic mice resulted in lymphatic, but not vascular, endothelial proliferation and vessel enlargement. Thus, VEGF-C induces selective hyperplasia of the lymphatic vasculature, which is involved in the draining of interstitial fluid and in immune function, inflammation, and tumor metastasis. VEGF-C may play a role in disorders involving the lymphatic system and may be of potential use in therapeutic lymphangiogenesis.

Animals↗
PubMed1997

The RNA-binding protein, TB-RBP, is the mouse homologue of translin, a recombination protein associated with chromosomal translocations.

The mouse RNA-binding protein, TB-RBP, suppresses translation in vitro and attaches mRNAs to microtubules by binding to conserved elements in the 3' untranslated regions of specific mRNAs. We have now purified TB-RBP from testicular and brain cytoplasmic extracts and cloned its cDNA. We find that the mouse TB-RBP cDNAs contain an open reading frame of 228 amino acids with a leucine zipper domain within its C terminus, a transmembrane helix, and a group of putative phosphorylation sites. TB-RBP shows 99% identity to the human protein, translin, a recombination hotspot-binding protein associated with chromosomal translocations [Aoki, K., Suzuki, K., Sugano, T., Tasaka, T., Nakahara, K., Kuge, O., Omori, A. & Kasai, M. (1995) Nat. Genet. 10, 167-174]. As shown for translin, TB-RBP also binds to single-stranded DNAs containing a broad range of consensus sequences, many of which are similar to the Y and H RNA-binding sequences. Recombinant TB-RBP was synthesized and an antiserum was prepared against the recombinant protein. The identity between translin and TB-RBP was confirmed by demonstrating that immunoprecipitation of TB-RBP from testicular extracts abolished formation of the RNA-TB-RBP complex. Based upon its DNA binding to target sequences in clustered breakpoint regions, we propose that TB-RBP may be involved in DNA recombination or DNA repair in male germ cells.

Amino Acid Sequence↗
PubMed1997

Upregulation of aquaporin-2 water channel expression in chronic heart failure rat.

Aquaporin-2 (AQP2) mediates vasopressin-regulated collecting duct water permeability. Chronic heart failure (CHF) is characterized by abnormal renal water retention. We hypothetized that upregulation of aquaporin-2 water channel could account for the water retention in CHF. Male rats underwent either a left coronary artery ligation, a model of CHF, or were sham operated. 31-33 d after surgery, mean arterial pressure (MAP) and cardiac output were measured in conscious animals, and the animals were killed 24 h later. Cardiac output (CO) and plasma osmolality were significantly decreased and plasma vasopressin increased in the CHF as compared to the sham-operated rats. Both mRNA and protein AQP2 were significantly increased in the kidneys of the CHF rats. The effect of oral administration of a nonpeptide V2 vasopressin receptor antagonist, OPC 31260, was therefore investigated. OPC 31260 induced a significant increase in diuresis, decrease in urinary osmolality, and rise in plasma osmolality in the OPC 31260-treated CHF rats as compared to untreated CHF rats. The mRNA and protein AQP2 were significantly diminished in both cortex and inner medulla of the treated CHF rats. In conclusion, an early upregulation of AQP2 is present in CHF rats and this upregulation is inhibited by the administration of a V2 receptor antagonist. The results indicate a major role for vasopressin in the upregulation of AQP2 water channels and water retention in experimental CHF in the rat.

Animals↗
PubMed1997

Protein kinase C isoform diversity in preconditioning.

Protein kinase C (PKC) appears to be a common intracellular effector and signal collector during cardiac preconditioning; however, it remains unknown whether agonists that activate different PKC isoforms are also linked to select aspects of myocardial protection. Using agonists that are known to activate unique combinations of PKC isoforms, we interrogated the relationship between isoform activation and the different aspects (pH, function, and viability) of endogenous myocardial protection. To study this, isolated rat hearts were subjected to ischemia-reperfusion (I/R) (20 min/40 min), without (control = Ctrl) or with receptor-dependent [phenylephrine (PE), 50 microM; adenosine (ADO), 125 microM] or -independent [phorbol myristate acetate (PMA), 100 nM] activation of PKC. Function, pH, and viability were assessed by rate pressure product (%RPP) and coronary flow (CF; ml/min), by 31P NMR, and by CF creatine kinase (CK; U/liter) leak, respectively. PMA, which activates PKC delta but not eta, resulted in intracellular pH (pHi) and viability protection, but did not protect against postischemic myocardial stunning. ADO, which activates PKC eta but not delta, protects against stunning, but not acidosis or necrosis. PE, which activates PKC delta and eta, provided global myocardial protection against necrosis, acidosis, and stunning. Different PKC isoforms may be linked to distinct aspects of myocardial protection. Targeted activation of PKC isoforms may allow precise mechanistic application of preconditioning-like myocardial protection.

Animals↗