Myasthenia gravis: pathogenesis and therapeutic approach on the basis of molecular structure and immunogenicity of acetylcholine receptor

Recent research for myasthenia gravis has been advanced by the availability of primary sequence of acetylcholine receptor (AChR) precursor and AChR transmembrane topography. (1) Synthetic peptides of AChR alpha-subunit defined myasthenogenic sites recognized by blocking or modulating antibody; their capability of inducing an animal model suggests that synthetic antigens contain not only B-cell sites but also T-cell sites which interact with restricted MHC class II molecules. (2) In view of the conformation-dependent B-cell site expected at beta-turn and the MHC-restricted T-cell site expected at amphipathic alpha-helix, conformationally modified peptides were synthesized by linking them; some were in combination with artificially sequenced peptide to favor an enhanced beta-turn. (3) Experiments by the use of these synthetic peptides demonstrated that such antigens were enhanced in myasthenogenicity. However, the immunogenic conformation for the induction of animal model did not necessarily assume that for the detection of antibody in native AChR-immunized rats. (4) Peptides synthesized to assume specifically for binding with antibody were used as a tool for immunoadsorption via plasma perfusion in myasthenic patients, resulting in clinical improvement.     

Monolithic folded pendulum accelerometers for seismic monitoring and active isolation systems

A new class of very low noise low-frequency force-balance accelerometers is presented. The device has been designed for advanced mirror isolation systems of interferometric gravitational wave detectors. The accelerometer consists of a small monolithic folded pendulum with 2 s of natural period and an in-vacuum mechanical quality factor of 3000. The folded pendulum geometry, combined with the monolithic design, allows a unique 0.01% cross-axis residual coupling. Equipped with a high-resolution capacitance position sensor, it is capable of a noise-equivalent inertial displacement of 1-nm root mean square integrated over all the frequencies above 0.01 Hz. The main features of this new accelerometer are here reviewed. New possible applications of monolithic folded pendula in geophysical instrumentation are discussed.     

Electron microscopic observation of the sagittal structure of Drosophila mature sperm

Observation of sperm development and determination of their morphological characteristics are very important to the understanding of phylogenetic relationships and the study of sperm function during fertilization. Although ultrastructural studies of sperm development in the testes of the fruit fly Drosophila have been performed, there are few reports describing electron microscopic morphology of mature sperm, that is, those released from the testes to the seminal vesicles. Here, we present the first report of the sagittal organization of Drosophila sperm head and neck regions by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The head and tail structures of a mature sperm, for example, the acrosome, nucleus, and flagellum, were easy to distinguish by the morphological characteristics of the sperm surface by SEM. The morphological relationships between the surface and internal structures of mature sperm were confirmed by observing longitudinal sections with TEM. Our approach overcame the technical difficulties involved in sample preparation for electron microscopic observation of the Drosophila mature sperm head, and therefore, this study serves as an important foundation for future genetic dissection of sperm ultrastructure and function in male sterile mutants. Microsc. Res. Tech. 77:661–666, 2014. © 2014 Wiley Periodicals, Inc.     

Stress-dependence of the permeability and porosity of sandstone and shale from TCDP Hole-A

We utilize an integrated permeability and porosity measurement system to measure the stress dependent permeability and porosity of Pliocene to Pleistocene sedimentary rocks from a 2000 m borehole. Experiments were conducted by first gradually increasing the confining pressure from 3 to 120 MPa and then subsequently reducing it back to 3 MPa. The permeability of the sandstone remained within a narrow range (10^?14–10^?13 m²). The permeability of the shale was more sensitive to the effective confining pressure (varying by two to three orders of magnitude) than the sandstone, possibly due to the existence of microcracks in the shale. Meanwhile, the sandstone and shale showed a similar sensitivity of porosity to effective pressure, whereby porosity was reduced by about 10–20% when the confining pressure was increased from 3 to 120 MPa. The experimental results indicate that the fit of the models to the data points can be improved by using a power law instead of an exponential relationship. To extrapolate the permeability or porosity under larger confining pressure (e.g. 300 MPa) using a straight line in a log–log plot might induce unreasonable error, but might be adequate to predict the stress dependent permeability or porosity within the experimental stress range. Part of the permeability and porosity decrease observed during loading is irreversible during unloading.     

Molecular biology and immunology of acetylcholine receptor in relation to myasthenia gravis

In search for the myasthenogenic sites in the molecular structure of acetylcholine receptor (AChR) alpha-subunit, the conformation-dependent B-cell epitopes, and the MHC class II-restricted, immune cofactors-modified T-cell epitopes were studied. Using the peptides synthesized corresponding to AChR amino acid sequence, the alpha 183-200 (as an antigen to raise "blocking antibody") and the alpha 70-90, alpha 125-147 and alpha 67-76 with alpha 107-116 (as antigens to raise "binding antibody") were found immunogenic in the induction of the disease in animals. Phenotypic changes in the T-cell lineages in the thymus were discussed. An impairment of excitation-contraction coupling in some of myasthenic muscles was attributed to a defect caused by antibodies raised against ryanodine receptor protein. Myasthenia gravis patients' sera containing anti-ryanodine receptor antibodies inhibited the calcium-induced release of calcium in response to caffeine in human rhabdomyosarcoma cell line. Buffalo/Mna rats with spontaneous benign thymoma showed (1) ryanodine receptor expressed in the thymic epithelial cells, (2) anti-ryanodine receptor antibodies in serum, and (3) reduced twitch and tetanic force without abnormality in synaptic transmission and muscle membrane properties. It is suggested that thymic epithelial cell and skeletal muscle share common ryanodine receptor antigen. The finding seen in this rat strain can be a counterpart of the feature reflecting an immune attack directed against a compartment of skeletal muscle in myasthenia gravis.     

Resection of malignant fibrous histiocytoma invading the thoracic aorta

We report a case of surgically resected malignant fibrous histiocytoma which arose in the posterior mediastinum. Tumor removal with the required sufficient-margin and the resection of the affected thoracic aorta, led to flaccid paraplegia below the tenth thoracic level. This patient is now surviving with no evidence of recurrence at 42 months after the operation. Although malignant fibrous histiocytoma in the thorax generally shows a poor prognosis, this patient with complete resection could have a relatively long survival.     

Bidirectional optical subassembly with prealigned silicon microlens and laser diode

We have succeeded in developing a low-cost bidirectional optical subassembly chip using a silicon microlens for fiber-to-the-home application. The main optical elements of the bidirectional function were automatically aligned and integrated on a silicon optical bench. The cost of subassembly was markedly lowered both by reducing the part number and simplifying the assembly process. The prototype bidirectional optical component was successfully fabricated on the basis of the proposed chip. A receiver minimum sensitivity of -28.5 dBm was experimentally demonstrated even at 75 /spl deg/C.     

The System Bi2O3-SiO2

The Bi₂O₃-rich side of the system Bi₂O₃-SiO₂ was studied with powder X-ray diffraction and differential thermal analysis. In the composition 6Bi₂O₃. x SiO₂, the metastable γ phase (bcc) was observed to exist over the range of 0 < x ≤ 1. In most of the compositions studied, metastable phases of water-quenched melts transformed into another metastable phase before reaching stable phases. A modification of the phase diagram is proposed.     

Phase Transformation Kinetics in the System Bismuth Oxide-Zirconia

The effect of ZrO₂ addition on the phase transformation of Bi₂O₃ was studied with powder X-ray diffraction and differential thermal analysis. Samples containing higher than a few mole percent ZrO₂ were obtained as the metastable β phase (tetragonal) at room temperature when they were cooled at 20°C/min from 800°C where the δ phase (fcc) is stable. When the same samples were cooled at the same rate from 1000°C, which is above the solidus, they formed the stable α phase (monoclinic) at room temperature. Evidence for the relatively higher solubility of ZrO₂ in the α phase is discussed to explain this observation.