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Yang Z Cerniway RJ Byford AM Berr SS French BA Matherne GP 《American journal of physiology. Heart and circulatory physiology》2002,282(3):H949-H955
Previous studies have shown that high-level (300-fold normal) cardiac overexpression of A1-adenosine receptors (A1-ARs) in transgenic (TG) mice protects isolated hearts against ischemia-reperfusion injury. However, this high level of overexpression is associated with bradycardia and increased incidence of arrhythmia during ischemia in intact mice, which interfered with studies to determine whether this line of TG mice might also be protected against myocardial infarction (MI) in vivo. For these studies, we therefore selected a line of TG mice that overexpresses the A1-AR at more moderate levels (30-fold normal), which affords cardioprotection in the isolated heart while minimizing bradycardia and arrhythmia during ischemia in intact mice. Wild-type (WT; n = 10) and moderate-level A1-AR TG (n = 10) mice underwent 45 min of left anterior descending coronary artery occlusion, followed by 24-h reperfusion. Infarct size and region at risk were determined by triphenyltetrazolium chloride and phthalo blue staining, respectively. Infarct size (% region at risk) in WT mice was 52 +/- 3%, whereas overexpression of A1-ARs in the TG mice markedly reduced infarct size to 31 +/- 3% (P < 0.05). Furthermore, contractile function (left ventricular ejection fraction) as determined by cardiac magnetic resonance imaging 24 h after MI was better preserved in TG vs. WT mice. Cardiac overexpression of A1-ARs reduces infarct size by 40% and preserves cardiac function in intact mice after MI. 相似文献
104.
Erami C Zhang H Ho JG French DM Faber JE 《American journal of physiology. Heart and circulatory physiology》2002,283(4):H1577-H1587
Previous studies suggesting that norepinephrine is directly trophic for the vascular wall have been confounded by concomitant hemodynamic disturbances. Herein, a microcatheter connected to an osmotic minipump was implanted adjacent to the rat carotid for 2-wk perivascular suffusion of agents at systemic levels ~1,000 times below the threshold for altering arterial pressure. Norepinephrine decreased lumen and adventitial areas and circumference by 10, 14, and 5%, respectively (all P < 0.05); a nonsubtype-specific alpha(1)-adrenoceptor (AR) antagonist had no effect. When begun at the time of balloon injury, 2-wk norepinephrine increased lumen loss by 45%, increased neointimal area by 64% and collagen content by 33%, and reduced vessel circumference by 5% (all P < 0.05). alpha(1)-AR antagonists decreased neointimal area by 33% (all P < 0.05). alpha(1)A-AR antagonist reduced lumen loss by 70%, neointimal area by 54%, circumference decline by 84%, and adventitial thickening by 87% (all P < 0.05), whereas alpha(1B)-, alpha(1D)-, alpha(2)- and beta-AR antagonists were without effect. These are the first in vivo studies demonstrating that norepinephrine is directly trophic for the vascular wall and augments injury-induced intimal lesion growth. 相似文献
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The heteromeric lymphotoxin alphabeta ligand (LT) binds to the LTbeta receptor (LTbetaR) and provides an essential trigger for lymph node (LN) development. LTbetaR signaling is also critical for the emergence of pathological ectopic lymph node-like structures and the maintenance of an organized splenic white pulp. To better understand the role of LT in development, the expression patterns of LTbeta and LTbetaR mRNA were examined by in situ hybridization in the developing mouse embryo. Images of LTbeta ligand expression in developing peripheral LN in the E18.5 embryo revealed a relatively early phase structure and allowed for comparative staging with LN development in rat and humans. The LTbetaR is expressed from E16.5 onward in respiratory, salivary, bronchial, and gastric epithelium, which may be consistent with early communication events between lymphoid elements and epithelial specialization over emerging mucosal LN. Direct comparison of mouse fetal and adult tissues by FACS analysis confirmed the elevated expression of LTBR in some embryonic epithelial layers. Therefore, surface LTBR expression may be elevated during fetal development in some epithelial layers. 相似文献
108.
Ducros V Demuth K Sauvant MP Quillard M Caussé E Candito M Read MH Drai J Garcia I Gerhardt MF;SFBC Working group on homocysteine. French Society for Clinical Biology 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,781(1-2):207-226
It is now widely accepted that increased total plasma homocysteine (tHcy) is a risk factor for cardiovascular disease. Hyperhomocysteinemia can be caused by impaired enzyme function as a result of genetic mutation or vitamin B (B(2), B(6), B(9), B(12)) deficiency. A lot of methods are now available for tHcy determination. High-pressure liquid chromatography (HPLC) with fluorescence detection are at present the most widely used methods but immunoassays, easier to use, begin to supplant in-house laboratory methods. In order to help with the choice of a main relevant homocysteine analytical method, the characteristics, performances and limits of the main current methods are reviewed. One major drawback among all these available methods is the transferability which is not clearly established to date. The impact of both inter-method and inter-laboratory variations on the interpretation of the tHcy results are discussed. 相似文献
109.
We review the findings of a longitudinal study of transmission of the intracellular tick-borne bacterium Anaplasma phagocytophilum from sheep to Ixodes ricinus ticks under natural conditions of tick attachment in the UK. In this study, sheep-to-tick transmission efficiency varied
in a quadratic relationship with the number of adult ticks that were feeding on the sheep. We raise the hypothesis that this
relationship may be due to conflicting effects of the density of ticks on bacterial survival and target cell (neutrophil)
fluxes at the tick-host interface: in the same sheep at the same time, resistance to ticks was progressively inhibited with
increasing number of feeding adult ticks, and investigation of serological responses to tick antigens suggesting loss of resistance
may be associated with polarisation of host Th1 to Th2 type responses to ticks. We also raise the hypothesis that these properties,
with superimposed effects on tick survival, may mean that variation in tick density is an important causal factor of observed
variations in the force of A. phagocytophilum infection amongst different geographic foci.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
110.
Lee S Macquillan GC Keane NM Flexman J Jeffrey GP French MA Brochier J Price P 《Immunology and cell biology》2002,80(4):391-397
Type 1 (T1) cytokine responses are required for the clearance of hepatitis C virus by cytotoxic T lymphocytes, but can promote liver damage. Interferon-alpha (IFN alpha) can be expected to promote T1 cytokine responses, so treatment outcome may depend on the T1/T2 cytokine environment and levels of immune activation at baseline. This model was tested by monitoring immunological markers in a pilot study of treatment na?ve patients given IFN alpha 2b and ribavirin, with the aim of finding markers that predict virological outcome. Soluble (s) CD26/dipeptidyl peptidase IV enzyme activity and levels of sCD30, bioavailable IL-6, sTNF-RI, IL-1ra and nitrite/nitrate (NO(2)(-)/NO(3)(-)) were measured. Levels of IL-1ra and bioavailable IL-6 were lower in patients than controls and did not change with therapy. Treatment decreased sCD26/dipeptidyl peptidase IV enzyme activities and sCD30 levels and increased NO(2)(-)/NO(3)(-) levels. High baseline sCD30 levels predicted an early (P = 0.008) and sustained (P = 0.03) virological response to therapy, suggesting treatment may be more effective in patients with a predominant T2 profile. 相似文献