Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MEDIATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed1993

Large, deep layer pyramid-pyramid single axon EPSPs in slices of rat motor cortex display paired pulse and frequency-dependent depression, mediated presynaptically and self-facilitation, mediated postsynaptically.

1. In slices of rat sensorimotor cortex, dual intracellular recordings were obtained from 1,952 pairs of deep layer pyramidal neurons. Where action potentials in one neurone elicited excitatory postsynaptic potentials (EPSPs, n = 56) in the other, responses to different presynaptic firing rates and patterns and at different postsynaptic membrane potentials were recorded and on some occasions both neurons were filled with biocytin. 2. Slices were fixed, sectioned again at 60 microns, and incubated with Avidin horseradish peroxidase (HRP), which was then visualized using the 3,3'-diaminobenzidine tetrahydrochloride (DAB) method. All neurones reported here that were identified histologically were pyramidal cells with their somata in the deep layers (V and VI). 3. One in 70 of the tests performed revealed a synaptic connection, 25 of which were studied in detail. Mean EPSP amplitude was 1.67 +/- 1.66 (SD) mV, with some single sweep events as large as 9 mV. For some of the smaller EPSPs the amplitude distributions contained a clear peak around 0 mV, the coefficient of variation (CV) was large, and paired pulse facilitation was apparent. EPSPs with large average amplitudes displayed no apparent failures of transmission, EPSP amplitudes were fairly evenly distributed around the mean, CVs were small, and paired pulse depression was apparent in 2.5 mM extracellular Ca2+. When single sweeps were selected according to the size of the first EPSP, large second EPSPs were found to follow small first EPSPs and small second EPSPs to follow large first EPSPs. Paired pulse effects appeared, in the majority of tests, to be due to a change in presynaptic release probability. 4. Two EPSPs were recorded in three different extracellular Ca2+ concentrations. In 1 mM Ca2+, the first EPSP of a short interval pair was small and paired pulse facilitation was apparent. In 5 mM Ca2+, first EPSPs were between 2.5 and 4 times larger than in 1 mM Ca2+ and paired pulse depression was apparent. In all Ca2+ concentrations however, averaged third and fourth EPSPs of brief bursts were of similar amplitudes and smaller than second EPSPs. If presynaptic inhibition does contribute to paired pulse effects here, it is not overcome by a combination of raised extracellular Ca2+ and repetitive presynaptic firing. 5. These EPSPs displayed a wide range of time courses. The mean 10-90% rise time was 2.49 +/- 1.08 ms, the mean width at half amplitude was 15.39 +/- 5.42 ms (n = 22), and the mean EPSP latency was 1.59 +/- 0.68 ms (n = 18). (ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Neutrophil-mediated killing, opsonization, and serum-mediated killing of Escherichia coli K1 by neonatal rats.

Neonates are particularly susceptible to infection with Escherichia coli K1. To investigate the mechanisms which lead to this susceptibility, we examined: (a) the bactericidal activity of neutrophils; (b) opsonization, and (c) the bactericidal activity of serum in developing rats. Neutrophils from adult rats killed E. coli K1 more efficiently than did neutrophils from young animals. Opsonization of E. coli by serum of prematurely delivered rats was poor. Serum from prematurely delivered and term rats promoted growth of E. coli K1, while serum from adult rats killed greater than 95% of the organisms within 90 min. However, the mixture of heat-inactivated serum from adult rats plus serum from prematurely delivered rats killed E. coli K1.

Animals↗
PubMed2000

Bleomycin-mediated pulmonary toxicity: evidence for a p53-mediated response.

Bleomycin damages DNA and causes lung injury and fibrosis. To determine whether bleomycin is associated with the appearance of DNA damage-inducible proteins, C3H mice received either 0.4 mg bleomycin or normal saline intratracheally and were killed 1 to 14 d later. The lungs were examined for expression of p53, p21(WAF1/PiCl), and proliferating cell nuclear antigen (PCNA) using immunohistochemistry and Western blotting. p53-positive cells first appeared at 5 d after treatment and peaked at 7 d; PCNA-positive cells appeared at 1 d after treatment and peaked at 7 d; and p21-positive cells appeared at 5 d and peaked at 9 d. Western blot analysis confirmed that bleomycin upregulated the DNA damage-inducible proteins in a similar fashion. This is the first evidence that bleomycin causes a p53-dependent response associated with acute injury in the lung.

Animals↗
PubMed1990

Transfection-mediated expression of a dominant cAMP-resistant phenotype in the opossum kidney (OK) cell line prevents parathyroid hormone-induced inhibition of Na-phosphate cotransport. A protein kinase-A-mediated event.

Sodium-phosphate cotransport in the PTH-responsive opossum kidney (OK) cell line is inhibited by PTH, cAMP, and activators of protein kinase C. In order to probe the role of cAMP, we stably transfected OK cells with an expression vector for a cAMP-binding mutation of the murine protein kinase A regulatory subunit. Two-dimensional electrophoresis of cAMP-binding proteins from transfected cells indicated a 20-fold overexpression of the mutant regulatory unit. Protein kinase A from these cells had a 20-fold increase in the concentration of cAMP required for half-maximal activation, 2.8 microM vs. 0.15 microM for wild type cells. In the transfected cells, Na-phosphate cotransport was insensitive to up to 1 mM 8-Br-cAMP and 1 microM PTH, while these same agonists caused a significant inhibition of transport in the wild type cells. The effects on Na-phosphate cotransport of the protein kinase C activators oleoyl-acetyl glycerol and tetradecanoyl-phorbol acetate, which were marked in the wild type cells, were still present, although attenuated, in the transfected mutants. With prolonged passage, the cAMP-insensitive phenotype reverted to wild type cAMP sensitivity despite continued selection for the cotransfected neo marker. The revertant cells had a normal cAMP requirement for half-maximal activation of protein kinase A, 0.13 microM, and the PTH and cAMP-sensitive inhibition of Na-phosphate cotransport was restored. We suggest that an intact and normally cAMP-sensitive protein kinase A pathway is an absolute requirement for PTH inhibition of Na-phosphate cotransport in the OK cell.

Animals↗
PubMed2006

TRAIL receptor-mediated JNK activation and Bim phosphorylation critically regulate Fas-mediated liver damage and lethality.

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family with potent apoptosis-inducing properties in tumor cells. In particular, TRAIL strongly synergizes with conventional chemotherapeutic drugs to induce tumor cell death. Thus, TRAIL has been proposed as a promising future cancer therapy. Little, however, is known regarding what the role of TRAIL is in normal untransformed cells and whether therapeutic administration of TRAIL, alone or in combination with other apoptotic triggers, may cause tissue damage. In this study, we investigated the role of TRAIL in Fas-induced (CD95/Apo-1-induced) hepatocyte apoptosis and liver damage. While TRAIL alone failed to induce apoptosis in isolated murine hepatocytes, it strongly amplified Fas-induced cell death. Importantly, endogenous TRAIL was found to critically regulate anti-Fas antibody-induced hepatocyte apoptosis, liver damage, and associated lethality in vivo. TRAIL enhanced anti-Fas-induced hepatocyte apoptosis through the activation of JNK and its downstream substrate, the proapoptotic Bcl-2 homolog Bim. Consistently, TRAIL- and Bim-deficient mice and wild-type mice treated with a JNK inhibitor were protected against anti-Fas-induced liver damage. We conclude that TRAIL and Bim are important response modifiers of hepatocyte apoptosis and identify liver damage and lethality as a possible risk of TRAIL-based tumor therapy.

Animals↗
PubMedDate not supplied

Trichinella spiralis infection is mediated by MCP-1 and MIP-2, while echinococcus granulosus is strongly mediated by MCP-1, but not MIP-2.

The chemokine supergene family are small proteins (8-10 KD) inducible in a number of pathophysiological processes. C-X-C family members are specific largely on neutrophils; whereas C-C chemokines act primarily on monocytes, T-cells, basophils and eosinophils. A wide variety of cell types produce chemokines in response to stimuli, including: infections, mitogens and inflammatory cytokines. Here we found that parasitic diseases, such as Trichinella spiralis and Echinococcus granulosus produce, MCP-1 (beta-chemokine) and MIP-2 (alpha-chemokine), or MCP-1, respectively. The specificity of production of these chemokines in the two parasitic diseases may help to achieve therapeutic strategies in inhibiting inflammation.

Journal Article↗
PubMed2003

Defects in T-cell-mediated immunity to influenza virus in murine Wiskott-Aldrich syndrome are corrected by oncoretroviral vector-mediated gene transfer into repopulating hematopoietic cells.

The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by immune dysfunction, thrombocytopenia, and eczema. We used a murine model created by knockout of the WAS protein gene (WASP) to evaluate the potential of gene therapy for WAS. Lethally irradiated, male WASP- animals that received transplants of mixtures of wild type (WT) and WASP- bone marrow cells demonstrated enrichment of WT cells in the lymphoid and myeloid lineages with a progressive increase in the proportion of WT T-lymphoid and B-lymphoid cells. WASP- mice had a defective secondary T-cell response to influenza virus which was normalized in animals that received transplants of 35% or more WT cells. The WASP gene was inserted into WASP- bone marrow cells with a bicistronic oncoretroviral vector also encoding green fluorescent protein (GFP), followed by transplantation into irradiated male WASP- recipients. There was a selective advantage for gene-corrected cells in multiple lineages. Animals with higher proportions of GFP+ T cells showed normalization of their lymphocyte counts. Gene-corrected, blood T cells exhibited full and partial correction, respectively, of their defective proliferative and cytokine secretory responses to in vitro T-cell-receptor stimulation. The defective secondary T-cell response to influenza virus was also improved in gene-corrected animals.

Animals↗
PubMed2005

Src family kinase-mediated and Erk-mediated thromboxane A2 generation are essential for VWF/GPIb-induced fibrinogen receptor activation in human platelets.

The binding of von Willebrand factor (VWF) to the platelet membrane glycoprotein Ib-IX (GPIb-IX) results in platelet activation. In this study, we sought to clarify previous conflicting reports and to elucidate the mechanism of activation and the precise role of extracellular signal-regulated kinase (Erk) in VWF-induced platelet activation. Erk2 is activated in platelets on stimulation with VWF/ristocetin in a time-dependent manner. VWF-induced Erk2 phosphorylation and thromboxane A2 (TXA2) release were completely blocked by PP2, an Src family kinase inhibitor, suggesting that Erk is downstream of Src family kinases. U73122, a phospholipase C inhibitor, also abolished TXA2 generation and Erk phosphorylation. Although VWF fostered the agglutination of platelets regardless of any additional treatment, the inhibition of mitogen-activated protein kinase kinase (MEK) with U0126 abolished VWF-induced platelet aggregation and thromboxane production in non-aspirin-treated washed platelets. However, in platelets treated with aspirin, VWF failed to cause any aggregation. Thus, we conclude that VWF stimulation of platelets results in phospholipase A2 activation through Erk stimulation and that Src family kinases and phospholipase C play essential roles in this event. We further conclude that VWF-induced platelet aggregation does not directly depend on Erk activation but has an absolute requirement for Src/Erk-mediated TXA2 generation.

Blood Platelets↗