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Extensive Accumulation (extensive + accumulation)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Alternaria alternata AT Toxin Induces Programmed Cell Death in Tobacco

JOURNAL OF PHYTOPATHOLOGY, Issue 10 2009
Elena T. Yakimova
Abstract Detached tobacco leaves were infiltrated with an AT toxin preparation from the foliar pathogen Alternaria alternata tobacco pathotype. The AT toxin preparation caused formation of necrotic lesions within 5 days post-infiltration in a concentration-dependent manner. Cell death was accompanied by increased levels of the stress metabolites hydrogen peroxide, malondialdehyde, free proline and by enhanced total protease activity. Lesion development and the production of stress metabolites were suppressed if the infiltration site was pre-infiltrated with caspase-specific peptide inhibitors (irreversible caspase-1 inhibitor acyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD-CMK) and the broad range caspase inhibitor benzyoxycarbonyl-Asp-2,6-dichlorobenzoyloxymethylketone (Z-Asp-CH2-DCB)), the serine protease inhibitor N,-p-tosyl- l -lysine chloromethylketone and the polyamine spermine. Extensive accumulation of reactive oxygen species (ROS), as determined by staining with 3-3,-diaminobenzidine and 2,,7,-dichlorofluorescein diacetate, was found in the AT toxin-challenged lesions. The data show that AT toxin-induced cell death in tobacco is a type of programmed cell death in which caspase-like proteases and ROS signalling play a prominent role. [source]

PAMAM dendrimer-based contrast agents for MR imaging of Her-2/neu receptors by a three-step pretargeting approach

MAGNETIC RESONANCE IN MEDICINE, Issue 4 2008
Wenlian Zhu
Abstract Pretargeting of receptors is a useful approach in molecular imaging and therapy to reduce background noise or toxicity and enhance selectivity. In this study a three-step pretargeting approach that includes a biotinylated antibody, avidin/streptavidin, and a biotinylated imaging agent is described. A PAMAM dendrimer generation 4 (G4D)-based MRI T1 agent biotin-G4D-DTPA-Gd (bG4D-Gd) and its sister compound with remaining free surface amine groups blocked by succinic anhydride to reduce positive charges (bG4D-Gd-SA) were synthesized. Limited selective enhancement in MRI was observed in a Her-2/neu mouse tumor xenograft by this three-step pretargeting approach that includes biotinylated trastuzumab, avidin and bG4D-Gd, or bG4D-Gd-SA. However, these dendrimer-based MRI agents with molecular weight around 29 kD reached and remained in the tumor through the enhanced permeability and retention effect. Prolonged and extensive accumulation of both bG4D-Gd and b-G4-Gd-SA in the kidneys was also observed. Magn Reson Med, 2008. © 2008 Wiley-Liss, Inc. [source]

Mutation in BAG3 causes severe dominant childhood muscular dystrophy,

ANNALS OF NEUROLOGY, Issue 1 2009
Duygu Selcen MD
Objective Myofibrillar myopathies (MFMs) are morphologically distinct but genetically heterogeneous muscular dystrophies in which disintegration of Z disks and then of myofibrils is followed by ectopic accumulation of multiple proteins. Cardiomyopathy, neuropathy, and dominant inheritance are frequent associated features. Mutations in ,B-crystallin, desmin, myotilin, Zasp, or filamin-C can cause MFMs and were detected in 32 of 85 patients of the Mayo MFM cohort. Bag3, another Z-disk,associated protein, has antiapoptotic properties, and its targeted deletion in mice causes fulminant myopathy with early lethality. We therefore searched for mutations in BAG3 in 53 unrelated MFM patients. Methods We searched for mutations in BAG3 by direct sequencing. We analyzed structural changes in muscle by histochemistry, immunocytochemistry, and electron microscopy, examined mobility of the mutant Bag3 by nondenaturing electrophoresis, and searched for abnormal aggregation of the mutant protein in COS-7 (SV-40 transformed monkey kidney fibroblast-7) cells. Results We identified a heterozygous p.Pro209Leu mutation in three patients. All presented in childhood, had progressive limb and axial muscle weakness, and experienced development of cardiomyopathy and severe respiratory insufficiency in their teens; two had rigid spines, and one a peripheral neuropathy. Electron microscopy showed disintegration of Z disks, extensive accumulation of granular debris and larger inclusions, and apoptosis of 8% of the nuclei. On nondenaturing electrophoresis of muscle extracts, the Bag3 complex migrated faster in patient than control extracts, and expression of FLAG-labeled mutant and wild-type Bag3 in COS cells showed abnormal aggregation of the mutant protein. Interpretation We conclude mutation in Bag3 defines a novel severe autosomal dominant childhood muscular dystrophy. Ann Neurol 2008 [source]

Eosinophils are activated in middle ear mucosa and middle ear effusion of patients with intractable otitis media associated with bronchial asthma

CLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2001
Y. Iino
Background Although patients with intractable otitis media associated with bronchial asthma have extensive accumulation of eosinophils in the middle ear mucosa and middle ear effusion, systematic histological and immunohistochemical studies have not been performed. Objectives To clarify the pathogenesis of middle ear diseases, we carried out immunohistochemical studies on middle ear specimens, particularly focusing on the characteristics of accumulated eosinophils. Methods Middle ear specimens obtained from eight adult patients and from 17 controls were immunohistochemically stained using monoclonal antibodies against EG1, EG2, mast cell tryptase, IgA and IgE. The concentration of eosinophil cationic protein (ECP) in middle ear effusion samples was also measured. Results In the asthmatic patients, severe round-cell infiltration was observed in the submucosa and most of the EG1-positive cells were also EG2-positive. In the control patients, the mucosa showed a fibrotic change with a few inflammatory cells, and EG1- or EG2-positive cells were quite few. The expression of IgE was found not only on the surface of mast cells but also within the plasma cells in the asthmatic patients, and the number of IgE-positive cells was about twice as high as that of mast cells. A significantly higher concentration of ECP was noted in middle ear effusion obtained from the asthmatic patients than that from the control patients. Conclusion Most of the eosinophils in the middle ear mucosa and middle ear effusion were activated, resulting in degranulation and release of ECP, and local IgE production occurs in the middle ear mucosa, indicating that the intractable inflammation is closely associated with IgE-mediated late phase response with eosinophil accumulation. [source]