ABSTRACT
Photonic bandgap fibers have a critical constraint determined by wavelength. The principle of scale invariance requires that features remain unchanged even as the scale of an object changes. This paper introduces a new concept for fractal photonic crystal fibers integrating these two. Our simulation confirmed single-mode transmission is possible for a fiber whose core diameter exceeds 35 times the wavelength.
ABSTRACT
MuSK antibody-positive myasthenia gravis (MuSK-MG) accounts for 5 to 15% of autoimmune MG. MuSK and LRP4 are coreceptors for agrin in the signaling pathway that causes clustering of acetylcholine receptor (AChR). MuSK also anchors the acetylcholinesterase (AChE)/collagen Q (ColQ) complex to the synaptic basal lamina. We previously reported that anti-MuSK antibodies (MuSK-IgG) block binding of ColQ to MuSK and cause partial endplate AChE deficiency in mice. We here analyzed the physiological significance of binding of ColQ to MuSK and block of this binding by MuSK-IgG. In vitro plate-binding assay showed that MuSK-IgG blocked MuSK-LRP4 interaction in the presence of agrin. Passive transfer of MuSK-IgG to Colq-knockout mice attenuated AChR clustering, indicating that lack of ColQ is not the key event causing defective clustering of AChR in MuSK-MG. In three MuSK-MG patients, the MuSK antibodies recognized the first and fourth immunoglobulin-like domains (Ig1 and Ig4) of MuSK. In two other MuSK-MG patients, they recognized only the Ig4 domain. LRP4 and ColQ also bound to the Ig1 and Ig4 domains of MuSK. Unexpectedly, the AChE/ColQ complex blocked MuSK-LRP4 interaction and suppressed agrin/LRP4/MuSK signaling. Quantitative analysis showed that MuSK-IgG suppressed agrin/LRP4/MuSK signaling to a greater extent than ColQ.
Subject(s)
Acetylcholinesterase/metabolism , Agrin/metabolism , Autoantibodies/pharmacology , Collagen/metabolism , LDL-Receptor Related Proteins/metabolism , Muscle Proteins/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Cholinergic/metabolism , Signal Transduction/drug effects , Acetylcholinesterase/genetics , Animals , Autoantibodies/immunology , Cell Line , Collagen/genetics , Epitopes/immunology , Gene Expression Regulation/drug effects , Humans , Immunization, Passive , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Mice , Mice, Knockout , Models, Biological , Muscle Proteins/genetics , Neuromuscular Junction/genetics , Neuromuscular Junction/metabolism , Protein Binding , Protein Interaction Domains and Motifs , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/chemistry , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/immunology , Receptors, Cholinergic/chemistry , Receptors, Cholinergic/genetics , Receptors, Cholinergic/immunology , Receptors, Nicotinic/genetics , Receptors, Nicotinic/metabolismABSTRACT
A 28-year-old man was admitted to our hospital because of severe headache and diplopia. Enhanced CT of the head revealed defects of contrast enhancement in the superior sagittal sinus and the right transverse sinus. Accordingly, he was diagnosed as suffering from cerebral venous thrombosis. The patient made a good recovery after receiving anticoagulant therapy. Investigations revealed a high plasma lipoprotein (a) [Lp (a)] level of 142 mg/ dl. We thought that his high Lp (a) level was associated with a thrombotic tendency. His mother also had an elevated plasma Lp (a) level of 45 mg/dl. Cerebral venous thrombosis of unknown etiology is not rare. In such patients, we should investigate the plasma Lp (a) level.
