A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

Immunohistochemical study of epithelioid hemangioendothelioma in the leg: a case report

Epithelioid hemangioendothelioma is a relatively rare lesion. Although its histogenesis has been well described, its immunohistochemical characteristics remain controversial. A case of epithelioid hemangioendothelioma of the soft tissue of the right leg in a 67-year-old Chinese woman is reported. Histologic findings of intracytoplasmic lumina in the tumor cells and positive immunostaining for vimentin, factor VIII-related antigen. CD34 and Ulex europaeus agglutinin 1 (UEA-1) were obtained, demonstrating differentiation of the tumor cells to endothelial cells, although staining for antibodies to cytokeratins AE1/AE3 and CAM5.2 was weak. CD34 as well as Factor VIII-related antigen is a useful marker of endothelial differentiation in this tumor. A review of the literature is also presented.     

Effect of platelet-activating factor on lipoprotein lipase and blood lipids

We investigated the effect of platelet-activating factor (PAF) and of the PAF specific antagonist CV-6209 on plasma lipid metabolism, and particularly on post-heparin plasma lipolytic activity in male Wistar rats. Lipoprotein lipase (LPL) activity was enhanced by intravenous injection of PAF before intravenous injection of heparin when the PAF dose was low (0.2 μg/kg). PAF activated hepatic triacylglycerol lipase (HTGL) activity dose-dependently. Plasma triacylglycerols (TG) significantly decreased with the activation of LPL and/or HTGL. Plasma total cholesterol (TC) and phospholipid (PL) levels decreased at a low dose of PAF (0.2 μg/kg), but increased when higher doses were used. The PAF antagonist CV-6209 partially reversed the PAF induced effects on HTGL, TC and PL. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989.     

Preparation of soluble TiCl3 catalysts by reduction of TiCl4 with Grignard reagents and their use for copolymerization of ethylene with propylene

Summary Preparations of soluble TiCl₃ catalysts by reduction of TiCl₄ with some types of Grignard reagents were carried out in halogenated hydrocarbon solvents by using appropriate ethers as donor. The soluble TiCl₃·MgX₂·ether complex catalysts and triisobutylaluminum as co-catalyst showed high activities for the copolymerization of ethylene with propylene. It was first found that the soluble TiCl₃·MgX₂·ether complex catalysts enhance the activities for the copolymerizations in the same manner as solid titanium catalysts supported on MgCl₂ which show high activities for homopolymerizations of olefin monomers. The copolymers obtained possessed low crystallinities. Also, the copolymers seem to contain microblock sequences and have outstandingly high tensile strength and elongation at break compared to copolymers by the conventional VOCl₃/Al(Et)_1.5Cl_1.5 catalyst system.     

Structural characterization of 1,2-polybutadiene by 13C-n.m.r. spectroscopy: 2. Sequence distribution of 1,2-unit in hydrogenated polybutadienes

The configurational sequences of 1,2-unit in a series of hydrogenated syndiotactic 1,2-polybutadienes were determined in relation to the sequence distribution of 1,2- and 1,4-units on the basis of the ¹³C-n.m.r. signal assignment of the methyl carbons. The observed triad distributions of 1,2- and 1,4-units and configurational distributions of the 1,2-unit are in good agreement with the calculated distributions from transition probabilities. The number average sequence lengths of the 1,2-unit and the 1,2-unit in the racemic addition are 5.7 to 8.0 and 4.1 to 5.4, respectively. From the extrapolation of the plot of the number average sequence length against the crystallinity of the starting 1,2-polybutadienes, the minimum sequence length for crystallization is estimated to be 3.7 for the 1,2-unit in the racemic addition.     

Design and implementation of a vehicle interface protocol using an IEEE 1394 network

A wide variety of in-vehicle devices such as camera sensors, navigation systems, telematics and communication equipments have been incorporated into a vehicle to realize Intelligent Transport Systems (ITS) applications. Because an efficient standardized network is required, ITS Data Bus (IDB) has been discussed to carry high-speed multimedia data for audio, video and other real-time ITS applications. For connecting devices in a standardized manner, the IDB network has architecture with a gateway called vehicle interface which is located between automaker’s proprietary network and the standardized IDB network. IEEE 1394 (also known as iLink or FireWire), which can transport multimedia data for consumer electronics, is a good candidate for IDB network. In this paper, we analyze the issues for existing AV/C protocol (application layer protocol over IEEE 1394) to comprise the IDB network. In addition, we designed and implemented the vehicle interface protocol as a higher layer of IEEE 1394 to address the AV/C protocol issues for realizing the whole IDB network architecture.     

Synthesis of polyamide-hydroxyapatite nanocomposites

Simultaneous one-pot syntheses of PA66 and HAp were carried out by extracting H₂O and CO₂ from PA66 monomers and HAp raw materials, respectively, resulting in the formation of a polyamide (PA) 66-hydroxyapatite (HAp) nanocomposite. During the process, a spherical nano-sized HAp particle was precipitated following dissolution of micro-sized CaHPO₄・2H₂O. The PA66 monomers were subsequently adsorbed onto the generated HAp product. Some of the adsorbed PA66 monomers formed a bound polymer on HAp, and an increase in the adhesiveness of the PA66-HAp interface was observed as the polymerization progressed. During this process, the synthesis of a nanocomposite from a micro-sized raw material and creation of an autonomous strong interface between the matrix and filler was achieved. In addition, the shape of the resultant HAp was controllable and could be modified to needle shape by the addition of F⁻ and Mg²⁺ ions to the raw material. HAp could also be changed to plate shape via octa-calcium phosphate (OCP). Notably, during the synthesis, the filler shape of the nanocomposite could be controlled to 0D (particle), 1D (needle), and 2D (plate).     

Combustion Mechanism of Azide Polymer

The combustion wave structure and thermal decomposition process of azide polymer were studied to determine the parameters which control the burning rate. The azide polymer studied was glycidyl azide polymer (GAP) which contains energetic – N₃ groups. GAP was cured with hexamethylene diisocyanate (HMDI) and crosslinked with trimethylolpropane (TMP) to formulate GAP propellant. From the experiments, it was found that the burning rate of GAP propellant is significantly high even though the adiabatic flame temperature of GAP propellant is lower than that of conventional solid propellants. The energy released at the burning surface of GAP propellant is caused by the scission of N N₂ bond which produces gaseous N₂. The heat flux transferred back from the gas phase to the burning surface is very small compared with the heat generated at the burning surface. The activation energy of the decomposition of the burning surface of GAP propellant, E_s, is determined to be 87 kJ/mol. The burning rate is represented by r = 9.16 × 10³ exp(–E_s/RT_s) where r (m/s) is burning rate, T_s (K) is the burning surface temperature, and R is the universal gas constant. The observed high temperature sensitivity of burning rate is correlated to the relationship of (∂T_s/∂T₀)_p = 0.481 at 5 MPa, where T₀ is the initial propellant temperature.     

Pulmonary arterial impedance analysis by the use of the oscillated assist flow

Pulmonary arterial impedance is an important and interesting characteristic that can be used to evaluate the physiological properties of the pulmonary vessel. However, power spectrum analysis of the pulmonary artery pressure and flow pattern have suggested that peak power in the relatively high frequency range (> 10 Hz) is significantly low; thus, we cannot analyze the vessel properties in the high frequency range. In this study, we used the newly developed vibrating flow pump (VFP), which can generate oscillated blood flow with a relatively high frequency (10-50 Hz) for right heart bypass, to evaluate the pulmonary arterial impedance pattern in the high frequency range. Acute animal experiments of the right heart bypass from the right atrium to the pulmonary artery using 6 healthy adult goats were performed. The flow pattern and pressure of the pulmonary artery, electrocardiograms (ECGs), and arterial and right atrial pressures were continuously monitored during the experiments. Spectral analysis of the hemodynamic parameters using the fast Fourier transform (FFT) method was performed to evaluate the spectral properties. The coherence function, transfer function, and phase patterns were calculated to analyze the impedance pattern in the relatively high frequency area. Previously, various investigators had tried to analyze the impedance patterns of the pulmonary artery; however, they could not analyze the impedance patterns over 10 Hz because the spectral patterns of the pulmonary flow do not have high power at high frequencies. These physiological analyses may be useful in designing the optimal pulmonary circulation.     

Structural characterization of 1,2-polybutadiene by 13C n.m.r. spectroscopy: 1. Signal assignment in hydrogenated polybutadienes

The configurational sequences of 1,2-unit in a series of hydrogenated syndiotactic 1,2-polybutadienes were investigated in relation to the sequence distribution of 1,2- and 1,4-units. The signals at 10.20–10.94 ppm were assigned to the methyl carbons in the isolated 1,2-unit, the 1,2-1,2 dyad sequence flanked by 1,4-unit, and the 1,2-1,2-1,2 triad sequence, in order of increasing magnetic field. The splittings due to the configurational sequences were observed in the signals, reflecting the dyad and triad sequences of the 1,2-unit, which were assigned by considering the relative intensity of the signals and also the chemical shifts of model polymers.