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11.
Kursad Erinc Mohamad H Yamani Randall C Starling Tim Crowe Robert Hobbs Corinne Bott-Silverman Gustavo Rincon James B Young Jingyuan Feng Daniel J Cook Nicholas Smedira E Murat Tuzcu 《The Journal of heart and lung transplantation》2005,24(8):1033-1038
BACKGROUND: Hypertension is a potential risk factor for allograft coronary vasculopathy. We evaluated the efficacy of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists, and their combined use, on the development of coronary vasculopathy in hypertensive heart transplant recipients. METHODS: Eighty-two heart transplant recipients underwent serial intravascular ultrasound (IVUS) analysis at baseline (within 1 month) and at 1 year after transplantation and were evaluated for the development of coronary vasculopathy. Patients were divided into 4 groups. Nineteen normotensive recipients received no treatment, control (Group A). Hypertensive patients were treated with either ACE inhibitors (Group B, n = 37), calcium antagonists (Group C, n = 16), or both (Group D, n = 10). RESULTS: We found a significant reduction in IVUS indices of coronary vasculopathy in heart transplant recipients who used a combination of an ACE inhibitor and a calcium antagonist compared with recipients who used either drug alone (p < 0.05). This synergistic efficacy was independent of the baseline indices evaluated in a multivariate regression analysis model and was noted despite comparable mean arterial pressure among the 3 hypertensive groups at 1 year, thus suggesting the presence of a synergistic anti-proliferative effect beyond the anti-hypertensive efficacy. CONCLUSIONS: The combined use of an ACE inhibitor and a calcium antagonist is more effective than the individual use of either drug alone on the development of coronary vasculopathy in cardiac transplant recipients. Large randomized clinical trials are warranted to evaluate such a synergistic efficacy. 相似文献
12.
13.
Allan L. Reiss Lisa Freund Leslie Plotnick Thomas Baumgardner Kathleen Green Amanda C. Sozer Mark Reader Corinne Boehm Martha B. Denckla 《Annals of neurology》1993,34(1):95-107
Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features. The results from comprehensive assessment of prepubertal monozygotic female twins discordant for X monosomy are presented. Zygosity was established with DNA Fingerprinting and no evidence of chromosomal mosaicism was seen in either child. Physical features in the affected twin were relatively mild with respect to the full spectrum of physical malformations and disabilities associated with Turner's syndrome. The neurobehavioral phenotypes of the twins were compared. Although both sisters scored in the superior range of intelligence, the affected twin's Performance IQ was 18 points less than her sister, whereas Verbal IQ showed only a 3-point difference between the sisters. Other relative differences were noted within the executive, visuospatial, and visuomotor domains of function. Behavioral evaluation indicated greater problems with attention, hyperactivity, and anxiety in the affected twin. Quantitative analysis of brain anatomy revealed evidence of both general and regional effects of X monosomy on neurodevelopment. Cerebrospinal fluid volume was increased by 25% in the affected twin compared with her sister with a corresponding decrease in gray matter volume. The right frontal, right parietal–occipital, and left parietal-perisylvian regions showed the greatest discrepancy between the sisters with respect to increased cerebrospinal fluid and decreased gray matter volumes in the twin with X monosomy. Differences in the posterior fossa were also noted with a 50% relative increase in the volumes of the fourth ventricle and cisterna magna and a 10 to 15% relative reduction in size of the cerebellar vermis, pons, and medulla in the affected twin. The association between the neurobehavioral and neuroanatomical findings in the affected twin is discussed. The unique nature of the naturally occurring genetic phenomenon seen in this twin pair provides an opportunity to more fully elucidate the neurobehavioral phenotype associated with X monosomy and Turner's syndrome. 相似文献
14.
Wijkstrom-Frei C El-Chemaly S Ali-Rachedi R Gerson C Cobas MA Forteza R Salathe M Conner GE 《American journal of respiratory cell and molecular biology》2003,29(2):206-212
The lactoperoxidase (LPO) antibiotic system is a well-characterized component of mammary and salivary gland secretions. Because LPO has been shown to function in ovine airways, human airway tissue and secretions were examined for the presence of LPO and its substrate, the anion thiocyanate (SCN-). In addition, human airway secretions were tested for LPO-mediated antibacterial activity, and LPO's activity was assessed against some human airway pathogens. The data showed that normal human airway secretions contained LPO enzyme activity (0.65 +/- 0.09 microg/mg secreted protein; n = 17), and Western blots of secretions demonstrated bands of the expected sizes for LPO. LPO mRNA was detected in trachea by sequencing PCR-amplified cDNA. SCN-, LPO's substrate, was present in undiluted airway secretions at concentrations sufficient for LPO catalysis (0.46 +/- 0.19 mM; n = 8), and diluted secretions contained antibacterial activity with LPO-like properties. Immunocytochemistry localized LPO to submucosal glands in human bronchi. Finally, as expected based on the known antibacterial spectrum of the LPO system, airway secretions showed LPO-dependent activity against Pseudomonas aeruginosa. In addition, the airway LPO system was shown to be effective against Burkholderia cepacia and Haemophilus influenzae. Thus, a functional LPO system exists in human airways and may contribute to airway host defense against infection. 相似文献
15.
Summary We have isolated two mutant strains, GSAr-4 and GSAr-5, which are able to grow on lactate in the presence of D-glucosamine. The glucosamine-resistant phenotype results from the cooperative effects of mutations in three loci, GAR1, GAR2 and GAR3. Both glucosamine resistant mutant strains were doubly mutant at gar1 gar2 (GSAr-4) or gar1 gar3 (GSAr-5). The mutants were also shown to exhibit glucose repression insensitive synthesis of NADH-cytochrome c reductase and cytochrome c oxidase. Glucose-repressible synthesis of the following enzymes was seen: succinic dehydrogenase, succinic: cytochrome c reductase, maltase (PNPGase), galactokinase, -galactokinase. The glucose-repression insensitivity segregates in association with the glucosamine resistance. 相似文献
16.
Stehle Robert Lionne Corinne Travers Franck Barman Tom 《Journal of muscle research and cell motility》1998,19(4):381-392
We have exploited solvent perturbation to probe the coupling of Ca2+ and rigor activation of the ATPase of myofibrils from rabbit psoas. Three techniques were used: overall myofibrillar ATPases
by the rapid-flow quench method; kinetics of the interaction of ATP with myofibrils by fluorescence stopped-flow; and myofibrillar
shortening by optical microscopy. Because of its extensive use with muscle systems, ranging from myosin subfragment-1 to muscle
fibres, we chose 40% ethylene glycol as the relaxing agent. At 4°C, the glycol had little effect on the myofibrillar ATPase
at low [Ca2+], but at high [Ca2+] the activity was reduced 50-fold, close to the level found under relaxing conditions, and there was no shortening. However,
the ATPase of chemically cross-linked myofibrils (permanently activated even without Ca2+) was reduced only 3–4-fold. The lesser reduction of the ATPase of permanently activated myofibrils was also observed in single
turnover experiments in which activation occurs by a few heads in the rigor state activating the remaining heads. The addition
of ADP, which also promotes strong head-thin filament interactions, also activated the ATPase but only in the presence of
Ca2+. Further experiments revealed that in 40% ethylene glycol, Ca2+ does initiate shortening but only with the aid of strong interactions and at temperatures above 15°C. This confirms that
in the organized and intact myofibril, Ca2+ and rigor activation are coupled, as proposed previously for regulated actomyosin subfragment-1.
This revised version was published online in September 2006 with corrections to the Cover Date. 相似文献
17.
Legoff J Amiel C Calisonni O Fromentin D Rajoely B Abuaf N Tartour E Rozenbaum W Bélec L Nicolas JC 《Journal of clinical immunology》2004,24(2):125-134
Immunodeficiency related to HIV may increase the incidence of EBV-associated lymphomas, by altering EBV-specific immune control and consequently favoring EBV reactivation. The aim of the present study was to assess the relationship between the decrease of EBV-specific cellular immunity and the increase of EBV reactivation in a prospective cohort of 72 unselected HIV-infected individuals. EBV-specific immunity was evaluated by a highly sensitive IFN-gamma ELISPOT assay using 22 peptides mimicking latent and lytic antigens, and circulating mononuclear (PBMC) EBV DNA load was quantified by real-time quantitative PCR. The mean circulating cell-associated EBV DNA load was higher in HIV-infected patients (639 copies/10(6) PBMC) than in healthy controls (21, n = 14) ( P = 0.005) and was higher in patients with CD4(+) T-cell count below 350/microL than that in patients harboring higher CD4(+) T-cell count (1112 vs. 389, P = 0.003). The mean intensity of EBV-specific cellular responses was lower in HIV-infected patients than in controls ( P = 0.001), even in patients with CD4(+) T-cell count above 350/-microL ( P = 0.007). The number of EBV peptides recognized was lower in HIV-infected patients than in controls (frequency: 0.44 vs. 0.67; P = 0.02), indicating reduced polyclonality in HIV-infected patients. The polyclonality was 1.5-fold lower in HIV-infected patients with CD4(+) T-cell count below 350/-microL ( P =0.007). For EBV load >1000 copies/10(6) PBMC, the levels of cell-associated EBV DNA and those of EBV-specific cellular immunity, either in intensity or in polyclonality, or both, were inversely correlated. These findings demonstrate early impairment of the EBV-specific cellular immune control with progressive increase of EBV reactivation in the course of HIV infection. These observations likely provide a basis for appreciating the risk to develop non-Hodgkin's lymphomas in HIV-infected individuals. 相似文献
18.
Etienne O Gasnier C Taddei C Voegel JC Aunis D Schaaf P Metz-Boutigue MH Bolcato-Bellemin AL Egles C 《Biomaterials》2005,26(33):6704-6712
The surface of medical devices is a common site of bacterial and fungal adhesion, first step to the constitution of a resistant biofilm leading frequently to chronic infections. In order to prevent such complications, several physical and chemical modifications of the device surface have been proposed. Here, we experiment a new type of topical antifungal coating using the layer-by-layer technique. The nanometric multilayer film obtained by this technique is functionalized by the insertion of a chromogranin A-derived antifungal peptide (CGA 47-66, chromofungin). We show that the embedded peptide keeps its antifungal activity by interacting with the fungal membrane and penetrating into the cell. In vitro studies demonstrate that such an antifungal coating is able to inhibit the growth of yeast Candida albicans by 65% and completely stop the proliferation of filamentous fungus Neurospora crassa. The cytotoxicity of such a coating was also assessed by growing human gingival fibroblasts at its surface. Finally, the antifungal coating of poly(methylmethacrylate), a widely used material for biomedical devices, is successfully tested in an in vivo oral candidiasis rat model. Taken together, these results assessed the functionalized multilayer films containing a new potent antifungal non-toxic peptide, as a novel and promising technique for local antifungal protection. 相似文献
19.
Besides intrinsic determinants of cell growth, epigenetic signals have been proposed to regulate development and maintenance of neurons. Here we provide evidence that cerebral astrocytes contribute significantly to the set of environmental influences that are required for long-term survival of neurons derived from the mammalian central nervous system. Cerebral astrocytes in serum-free culture express diffusible and non-diffusible neuron-supporting signals, including cell-adhesive neurite growth-promoting glycoproteins, diffusible neurotrophic factors as well as membrane-bound molecules that mediate cell contact interactions. The combination and synergistic interaction of these environmental signals markedly enhance the survival of brain neurons. While astroglia-derived cell-adhesive substrates that include a high molecular weight complex consisting of laminin β-chains and proteoglycan (Matthiessen et al., 1989) stimulate neurite outgrowth, they fail to enhance long-term neuronal survival when additional neurotrophic and cell-contact interactions are lacking. Astrocytes release a diffusible neurotrophic activity that, when permanently applied, maintains long-term survival of central neurons in culture. The soluble neurotrophic activity seems to interact synergistically with cell-bound signals which are also required for long-term survival and which are expressed by astrocytes and neurons, but not by fibroblasts. Among neurons from different brain areas, such as hippocampus, cerebral cortex and septum, regional differences in their responsiveness to the astroglial neurotrophic activity have been observed. 相似文献
20.
Peter Lane Corinne Burdet Fiona McConnell Antonio Lanzavecchia Elisabetta Padovan 《European journal of immunology》1995,25(6):1788-1793
We report the capacity of CD40 ligand (CD40L)-negative T cell clones to activate human B cells. CD40L-negative T cells induce a level of B cell proliferation 10–20% of that seen with normal T cells. The signal provided by the negative clones is synergistic with that derived from a CD40L transfectant, and restores B cell proliferation to normal levels, showing that CD40L-negative T cell clones are not inherently inhibitory for B cells. Although their capacity to induce proliferation was much reduced, CD40L-negative T cell clones were still strong inducers of B cell differentiation to plasma cells. This differentiation to plasma cells was inhibited by a CD40L transfectant. The data are discussed with regard to the normal in vivo mechanism for maintaining B cell memory and memory antibody responses to T-dependent antigens. 相似文献