Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The ability of recombinant human tumour necrosis factor-alpha (rec huTNF) to elicit cardiodepressor and vasodepressor effects in rat isolated tissues was investigated. 2. rec huTNF (3 x 10(-11)-3 x 10(-8) M) administered directly to the organ bath, caused a concentration-dependent relaxation of the isoprenaline-induced inotropic response in electrically stimulated rat left atria. This occurred within 20 min of administration. In contrast, rec huTNF was without effect on the chronotropic response to isoprenaline in isolated spontaneously beating atria. 3. rec huTNF (1 microgram kg-1) was also given systemically to rats and the atria studied in vitro. Only 60 min of rec huTNF pretreatment was sufficient to cause a marked attenuation of the isoprenaline-induced inotropic response. This effect was not further augmented when rats were pretreated with rec huTNF for 24 h. 4. In isolated aortic rings taken from rats 60 min after rec huTNF (1 microgram kg-1, i.v.) administration, there was no effect seen on the constriction induced by phenylephrine in either endothelium-intact or denuded tissues. In addition, any responses to L-arginine or NG-nitro-L-arginine methyl ester (L-NAME) administration were unaffected by rec huTNF pretreatment. 5. In aortic rings taken from rats 24 h after rec huTNF administration, the phenylephrine-induced constriction was significantly attenuated in tissues with an intact endothelium. Furthermore, the relaxation to subsequent L-arginine administration was greater in these tissues than in those saline-treated rats. In addition, in both endothelium-intact and denuded tissues, the vasoconstrictor response to L-NAME (10-3M) was significantly augmented. 6. These data suggest that rec huTNF possesses both cardiodepressant properties with a rapid onset of action and vasodepressant properties with a slow onset of action. The latter could be mediated through the induction of a non-constitutive form of the NO-synthase enzyme present within the vascular wall.
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PMID:The cardiodepressant and vasodepressant effects of tumour necrosis factor in rat isolated atrial and aortic tissues. 138 89

It has been clearly established that osteoclasts, which play a crucial role in bone resorption, differentiate from hematopoietic cells belonging to the monocyte/macrophage lineage in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). We have here investigated the M-CSF- and RANKL-induced osteoclastic differentiation of two distinct clones of the murine monocytic/macrophagic RAW 264.7 cell line, known as TIB-71 and CRL-2278, the latter cell clone being defective for the expression of the inducible nitric oxide synthase isoform in response to interferon-gamma or lipopolysaccharide. CRL-2278 cells demonstrated a more rapid osteoclastic differentiation than TIB-71 cells, as documented by morphology, tartrate-resistant acid phosphatase positivity, and bone resorption activity. The enhanced osteoclastic differentiation of CRL-2278 was accompanied by a higher rate of cells in the S/G2-M phases of cell cycle as compared to TIB-71. The analysis of nitric oxide synthase (NOS) isoforms clearly demonstrated that only neuronal NOS was detectable at high levels in CRL-2278 but not in TIB cells under all tested conditions. Moreover, the broad inhibitor of NOS activity L-NAME significantly inhibited osteoclastic differentiation of CRL-2278 cells. Altogether, these results demonstrate that a basal constitutive neuronal NOS activity positively affects the RANKL/M-CSF-related osteoclastic differentiation.
Anat Rec A Discov Mol Cell Evol Biol 2005 Oct
PMID:Different levels of the neuronal nitric oxide synthase isoform modulate the rate of osteoclastic differentiation of TIB-71 and CRL-2278 RAW 264.7 murine cell clones. 1614 87

Autoantibodies against recoverin, a Ca2+-binding protein found in patients with cancer-associated retinopathy (CAR syndrome), penetrate retinal cells and induce their apoptosis via a mitochondrial pathway. The goal of this study was to investigate whether the entry of anti-recoverin antibody into E1A.NR3 retinal cells causes a change in intracellular Ca2+. Intracellular Ca2+ was measured using the Ca2+-sensitive fluorescent dye Fura-2 AM in living E1A.NR3 retinal cells treated with anti-recoverin antibody Rec-1, patients' autoantibodies, and control rat and human IgG. The exposure of retinal cells to Rec-1 antibody and to the CAR patients' autoantibodies in vitro caused a significant increase in intracellular Ca2+, while non-specific antibodies did not induce such an effect. Co-treatment of the E1A.NR3 cells with Rec-1 in the presence of nifedipine, a L-type Ca2+ channel blocker, significantly suppressed the increase of Ca2+. Treatment with nifedipine also blocked changes in the anti-apoptotic protein bcl-xL and in expressions of the pro-apoptotic protein bax. Nifedipine-treated cells also showed a decrease in cytosolic cytochrome c release and a decrease in caspase 3 activation, compared to cells treated only with Rec-1 antibody. The increase in the antibody-induced Ca2+ is at least in part dependent on extracellular Ca2+. Nifedipine was found to inhibit the entry of Ca2+ into the cells and to protect them from Rec-1-induced apoptosis. Increased levels of intracellular Ca2+ may lead to retinal dysfunction and degeneration in the CAR syndrome. Our results provide a molecular basis for the use of Ca2+ blockers in the treatment of the CAR syndrome.
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PMID:Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells. 1642 15

Nitric oxide (NO) has been implicated in many pathophysiological situations in the lung, including hypoxia/reoxygenation. This work seeks to clarify the current controversy concerning the double protective/toxic role of endogenous NO under hypoxia/reoxygenation situations in the lung by using a nitric oxide synthase (NOS) inhibitor, in a novel approach to address the problems raised from assaults under such circumstances. A follow-up study was conducted in Wistar rats submitted to hypoxia/reoxygenation (hypoxia for 30 min; reoxygenation of 0 h, 48 h, and 5 days), with or without prior treatment using the nonselective NOS inhibitor L-NAME (1.5 mM, in drinking water). Lipid peroxidation, apoptosis level, protein nitration, in situ NOS activity and NO production (NOx) were analyzed. This is the first work to focus on the time-course effects of L-NAME in the adult rat lung submitted to hypoxia/reoxygenation. The results showed that after L-NAME administration, in situ NOS activity was almost completely eliminated and consequently, NOx levels fell. Lipid peroxidation and the percentage of apoptotic cells rose at the earliest reoxygenation time (0 h), but decreased in the later period (48 h and 5 days). Also nitrated protein expression decreased at 48 h and 5 days posthypoxia. These results suggest that NOS-derived NO exerts two different effects on lung hypoxia/reoxygenation injury depending on the reoxygenation time: NO has a beneficial role just after the hypoxic stimulus and a deleterious effect in the later reoxygenation times. Moreover, we propose that this dual role of NO depends directly on the producer NOS isoform.
Anat Rec (Hoboken) 2010 Dec
PMID:Endogenous nitric oxide can act as beneficial or deleterious in the hypoxic lung depending on the reoxygenation time. 2073 24

The aims of this study were to statistically reassess the likelihood that windborne spread of foot-and-mouth disease (FMD) virus (FMDV) occurred at the start of the UK 1967 to 1968 FMD epidemic at Oswestry, Shropshire, and to derive dose-response probability of infection curves for farms exposed to airborne FMDV. To enable this, data on all farms present in 1967 in the parishes near Oswestry were assembled. Cases were infected premises whose date of appearance of first clinical signs was within 14 days of the depopulation of the index farm. Logistic regression was used to evaluate the association between infection status and distance and direction from the index farm. The UK Met Office's NAME atmospheric dispersion model (ADM) was used to generate plumes for each day that FMDV was excreted from the index farm based on actual historical weather records from October 1967. Daily airborne FMDV exposure rates for all farms in the study area were calculated using a geographical information system. Probit analyses were used to calculate dose-response probability of infection curves to FMDV, using relative exposure rates on case and control farms. Both the logistic regression and probit analyses gave strong statistical support to the hypothesis that airborne spread occurred. There was some evidence that incubation period was inversely proportional to the exposure rate.
Vet Rec 2011 Sep 24
PMID:Reanalysis of the start of the UK 1967 to 1968 foot-and-mouth disease epidemic to calculate airborne transmission probabilities. 2184 85

Poly(A)-binding proteins are highly conserved among eukaryotes and regulate stability of mRNA and translation. Among C. elegans homologues, pab-1 mutants showed defects in germline mitotic proliferation. Unlike pab-1 mutants, pab-1 RNAi at every larval stage caused arrest of germline development at the following stage, indicating that pab-1 is required for the entire postembryonic germline development. This idea is supported by the observations that the mRNA level of pab-1 increased throughout postembryonic development and its protein expression was germline-enriched. PAB-1 localized to P granules and the cytoplasm in the germline. PAB-1 colocalized with CGH-1 and CAR-1 and affected their localization, suggesting that PAB-1 is a component of processing (P)-bodies that interacts with them. The mRNA and protein levels of representative germline genes, rec-8, GLP-1, rme-2, and msp-152, were decreased after pab-1 RNAi. Although the mRNA level of msp-152 was increased in cgh-1 mutant, it was also significantly reduced by pab-1 RNAi. Our results suggest that PAB-1 positively regulates the mRNA levels of germline genes, which is likely facilitated by the interaction of PAB-1 with other P-body components, CGH-1 and CAR-1.
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PMID:PAB-1, a Caenorhabditis elegans poly(A)-binding protein, regulates mRNA metabolism in germline by interacting with CGH-1 and CAR-1. 2436 95