The Ultrastructure of Tissue Damage by Amyloid Fibrils

Amyloidosis is a group of diseases that includes Alzheimer’s disease, prion diseases, transthyretin (ATTR) amyloidosis, and immunoglobulin light chain (AL) amyloidosis. The mechanism of organ dysfunction resulting from amyloidosis has been a topic of debate. This review focuses on the ultrastructure of tissue damage resulting from amyloid deposition and therapeutic insights based on the pathophysiology of amyloidosis. Studies of nerve biopsy or cardiac autopsy specimens from patients with ATTR and AL amyloidoses show atrophy of cells near amyloid fibril aggregates. In addition to the stress or toxicity attributable to amyloid fibrils themselves, the toxicity of non-fibrillar states of amyloidogenic proteins, particularly oligomers, may also participate in the mechanisms of tissue damage. The obscuration of the basement and cytoplasmic membranes of cells near amyloid fibrils attributable to an affinity of components constituting these membranes to those of amyloid fibrils may also play an important role in tissue damage. Possible major therapeutic strategies based on pathophysiology of amyloidosis consist of the following: (1) reducing or preventing the production of causative proteins; (2) preventing the causative proteins from participating in the process of amyloid fibril formation; and/or (3) eliminating already-deposited amyloid fibrils. As the development of novel disease-modifying therapies such as short interfering RNA, antisense oligonucleotide, and monoclonal antibodies is remarkable, early diagnosis and appropriate selection of treatment is becoming more and more important for patients with amyloidosis.     

Forensic discrimination of sheet glass by a refractive-index measurement and elemental analysis with synchrotron radiation X-ray fluorescence spectrometry.

Measurements of the refractive index (RI) and elemental analysis using synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) were applied to the forensic discrimination of sheet-glass samples from different origins. The refractive index was calculated from the matching temperature at which the glass fragments became invisible in silicone oil. Fragments smaller than 1 mm in maximum diameter were taken from each of 11 sheet glasses and subjected to analysis by SR-XRF. The XRF spectrum of these samples indicated that a comparison of 6 elements (Ca, Fe, Sr, Zr, Ba and Ce) was useful for the discrimination of sheet glasses. Cluster analysis was performed using 33 sets of SR-XRF data obtained by triplicate measurements for the 11 glasses. Comparing 528 pairs among 33 samples, 515 pairs could be correctly discriminated. The number of indistinguishable pairs could be reduced from 36 to 4 by comparing the SR-XRF data. Elemental analysis by SR-XRF could provide small glass fragments with a more evidential value than the solely measurement of only RI, through a significant improvement of the discrimination capability.     

Studies on the syntheses of azole derivatives. Part VIII. Photolysis of N-aryl-N-benzylearbamoyl azides [studies on the syntheses of heterocyclic compounds. Part CDXV

Photolysis of N-benzyl-N-phenylearbamoylazide (IVc) afforded 1-benzy 1-2-benzimidazolinone (Ic), 2-benzimidazolinone (IIe), 4-benzy 1-2-benzimidazolinone (IIe), and 5-benzy1-2-benzimidazo-linone (IIf)- The same reaction of N-benzyl-N-(4-chlorophenyl) carbamoyl azide (IVd) gave 3-benzyl-1-(phenylhydrazocarbonyl)-2-benzimidazolinone (VIb) besides the above four products. In the case of N-benzyl-4-(4-butoxyphenyl)carbamoyl azide (IVe), 1-benzy1-5-butoxy-2-benz-imidazolinone (1e), 5-butoxy-2-benzimidazolinone (IId), 5-benzy1-2-benzimidazolinone (IIf), and 4-benzy1-6-butoxy-2-benzimidazolinone (IIg).     

Internal surface polarity of regenerated cellulose gel depends on the species used as coagulant

We report the development of a new selective and specific electrochemical biosensor for bacterial lipolysaccharide (LPS). An electrode interface was constructed using a l-cysteine-gold nanoparticle (AuNpCys) composite to be immobilized by electrostatic interaction in the network of a poly(vinyl chloride-vinyl acetate maleic acid) (PVM) layer on a gold bare electrode. The impedimetric biosensor is fabricated by self-assembled CramoLL lectin on the PVM-AuNpCys-modified gold electrode through electrostatic interaction. CramoLL is used as the recognition interface. AFM images showed that LPS was specifically recognized on the PVM-AuNpCys-CramoLL system surface. The measurements of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) showed that the electrochemical response of a redox probe system (K(4)[Fe(CN)(6)](4-)/K(3)[Fe(CN)(6)](3-)) were blocked, due to the procedures of modified electrode with PVM-AuNpCys-CramoLL. In the majority of the experiments the lectin retained its activity as observed through its interaction with LPS from Escherichia coli, Serratia marcescens, Salmonella enterica and Klebsiella pneumoniae. The results are expressed in terms of the charge transfer resistance and current peak anodic using the EIS and CV techniques for the development of a biosensor for contamination by endotoxins. A new type of sensor for selective discrimination of LPS types with a high sensitivity has been obtained.     

Colloidal crystallization of thermo-sensitive gel spheres of poly (<Emphasis Type="Italic">N</Emphasis>-isopropyl acrylamide)

Morphology, phase diagram, and reflection spectroscopy of the colloidal crystals of thermo-sensitive gel spheres, poly (N-isopropylacrylamide) (224 nm in the hydrodynamic diameter at 25 °C) were studied. Giant colloidal single crystals formed at very low gel concentrations. Critical concentration of melting of gel spheres (0.8 wt.% without ion-exchange resins) decreased sharply to 0.01 wt.% as the gel suspension was deionized exhaustively with coexistence of the mixtures of cation- and anion-exchange resins and increased substantially as concentration of sodium chloride increased. These studies demonstrated that the colloidal crystallization takes place by the extended electrical double layers formed around the gel spheres in addition of the excluded-volume effect of the gels. Most of the researchers including the authors have believed that the crystallization of the gel spheres takes place by the excluded-volume effect, in other words, by the hard-sphere model, exclusively. However, the present work clarified that the colloidal interfaces, which are inevitable for the formation of the electrical double layers, are formed firmly between the water phase and gel spheres, though the gel spheres contain a lot of water molecules in the inner the sphere region.