ABSTRACT
We have characterized a panel of 6 monoclonal antibodies raised against human platelet talin by Western blotting, immune precipitation, and immunofluorescence, and shown that antibodies TA205 and TD77 disrupt actin stress fibers and focal adhesions, and inhibit cell motility when microinjected into human fibroblasts. Using a series of chick talin fusion proteins spanning the entire length of the molecule, we have mapped the epitopes recognized by these antibodies to the conserved N- and C-terminal regions of the protein. TA205 bound to an epitope contained within residues 139-433, a region which overlaps an F-actin binding site, and which shows homology with the ezrin/radixin/moesin family of cytoskeletal proteins. The epitope recognized by TD77 was located within the C-terminal region of the protein (residues 2269-2541) which also contains an F-actin binding site homologous to that in the yeast actin-binding protein SIa2p. To investigate the possibility that TD77 disrupts actin stress fibers by binding directly to the C-terminal actin binding site, additional talin fusion proteins were generated and analyzed for TD77 and actin binding. Fusion proteins containing residues 2269-2541, 2304-2541, and 2304-2463 all cosedimented with F-actin, whereas TD77 did not recognize the latter fusion protein. These results show that the C-terminal actin-binding site is distinct from the region recognized by the anti-functional antibody TD77, raising the possibility that it binds to a novel functionally important ligand-binding site in the talin molecule.
Subject(s)
Actins/physiology , Antibodies, Monoclonal/pharmacology , Cytoskeleton/ultrastructure , Talin/chemistry , Talin/immunology , Actins/drug effects , Actins/ultrastructure , Amino Acid Sequence , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/isolation & purification , Binding Sites , Cell Line , Cell Movement/drug effects , Cell Movement/physiology , Chickens , Cross Reactions , Cytoskeleton/drug effects , Epitopes/analysis , Fibroblasts , Glutathione Transferase , Humans , Lung , Mice , Microinjections , Molecular Sequence Data , Nematoda , Recombinant Fusion Proteins/immunology , Sequence Homology, Amino AcidABSTRACT
We have used new diagnostic criteria to define patients with the polyarteritis nodosa (PAN) group of vasculitis. These were the combination of a necrotising glomerulitis without diffuse deposits of immunoglobulins or complement components in a patient presenting with systemic disease and multi-organ involvement. Twenty-two patients who fulfilled these criteria presented to our unit between 1975 and 1982. The diagnosis of PAN was confirmed by traditional histological criteria in eight. We anticipate that the use of these criteria will lead to earlier diagnosis and thereby improve the management of this potentially lethal disorder.
Subject(s)
Glomerulonephritis/pathology , Kidney/pathology , Polyarteritis Nodosa/pathology , Adult , Aged , Biopsy , Female , Fluorescent Antibody Technique , Humans , Male , Middle Aged , Polyarteritis Nodosa/diagnosisSubject(s)
Laundering/history , Computers , Egypt , Europe , History, 18th Century , History, 19th Century , History, 20th Century , History, Ancient , HumansABSTRACT
PIP: Population growth rates in developing countries must be reduced sharply to prevent failure of general development programs. Family planning services must be linked with the larger developmental programs for each nation. Fertility control programs must reach the rural areas where 80% of the population of developing countries live. There will be need for family planning services for more than 1 billion women in the developing countries in the next 25 years. Successful new efforts in Pakistan, Thailand, Indonesia, and Taiwan are cited. Agency for International Development efforts over the last 10 years are cited.^ieng
