An update on the validation of whole slide imaging systems following FDA approval of a system for a routine pathology diagnostic service in the United States

Pathologists have used light microscopes and glass slides to interpret the histologic appearance of normal and diseased tissues for more than 150 years. The quality of both microtomes used to cut tissue sections and microscopes has improved significantly during the past few decades, but the process of rendering diagnoses has changed little. By contrast, major advances in digital technology have occurred since the introduction of hand held electronic devices, including the development of whole slide imaging (WSI) systems with software packages that can convert microscope images into virtual (digital) slides that can be viewed on computer monitors and via the internet. To date, however, these technological developments have had minimal impact on the way pathologists perform their daily work, with the exception of using computers to access electronic medical records and scholarly web sites for pertinent information to assist interpretation of cases. Traditional practice is likely to change significantly during the next decade, especially since the Federal Drug Administration in the USA has approved the first WSI system for routine diagnostic practice. I review here the development and slow acceptance of WSI by pathology departments. I focus on recent advances in validation of WSI systems that is required for routine diagnostic reporting of pathology cases using this technology.     

Antigenic identity of the capsule lipopolysaccharides,exopolysaccharides, and O-specific polysaccharides in Azospirillum brasilense

The antigenic identity (and close values of electrophoretic mobility) of capsular polysaccharides, exopolysaccharides, and O-specific polysaccharides was revealed in the Azospirillum brasilense strains Sp7 and Sp245 by the immunodiffusion and immunoelectrophoretic methods. Together with the literature data on the identity of the monosaccharides composition of these polymers, this gives evidence of the absence of a specific capsular antigen in the bacteria studied. Thus, extracellular Azospirillum brasilense polysaccharides are likely to represent O-antigenic lipopolysaccharide fragments excreted by the bacteria into the culture medium, and their identification as a capsule or as an exopolysaccharide depends on the strength of the attachment of these polysaccharides to the cell surface.     

Putative molecular mechanism of defensin interaction with the membrane of the sensory neuron

NP-1 defensin decreased effective charge transfer in the activation gating system of TTX-resistant (slow) sodium channels in a dose-dependent manner. The dissociation constant and Hill coefficient values were KD = 2 pM and X--0.9. Geometry of the NP-1 defensin molecule was built using its primary structure with three S-S briges and fully optimised in the framework of molecular mechanics method. The data obtained explain experimental results of stechiometry 1:1 due to ligand-receptor interaction by the only outward directed carboxyl group of Glu 14 which might form a hydrogen bond with a single binding site of non-identified defensin membrane receptor.     

Initiation of the 3′:5′-AMP-induced protein kinase A Iα regulatory subunit conformational transition. Part I. A202 and A326 are critical residues

Protein-ligand docking and molecular dynamics studies have shown that the key event initiated by 3′:5′-AMP binding to the A- and B-domains of protein kinase A Iα regulatory subunit is formation of a hydrogen bond between 3′:5′-AMP and A202(A326) (the residue in parentheses being from the B-domain). The A202(A326) amide group movement associated with the bond formation leads to reorganization of the phosphate binding cassette (PBC) (the short 3₁₀-helix becomes the long α-helix). This process results in L203(L327) displacement and finally causes hinge (B-helix) rotation. The L203(L327) displacement and packing into the hydrophobic pocket formed by the PBC and β2β3-loop also depends on the β2β3-loop conformation. The correct conformation is maintained by R, I, E, but not K at position 209(333) of the A- and B-domains. So, the R209K and R333K mutants have problems with reaching B-conformation. The apo-form of the 3′:5′-AMP-binding domain also undergoes transition from H- to B-conformation. In this case, the movement of A202(A326) amide group seems to be a result of reorganization of the PBC into a more stable α-helix.     

Molecular mechanisms of imidazole and benzene ring binding in proteins

Aromatic bonds of amino acid radicals play an important role in arrangement of protein primary structure. Previously, the existence of a number of preferable conformations of aromatic dimers was shown theoretically and experimentally, the best known of which are parallel-displaced and perpendicular T conformations. To reveal principles that define preference of various conformations for His-His and Phe-His dimers, non-empirical quantum-chemical calculations of diimidazole and benzene-imidazole were carried out. Calculations were performed using the 6-31G** basis with account for electronic correlations in frames of MP2 and MP4 methods of perturbation theory. Comparative analysis of energetic and geometric parameters of the systems points to the preference of stacking contact or classical hydrogen bond in diimidazole. On the contrary, T conformation is maximally advantageous for benzene-imidazole.     

Quantitative histophotometric study of liver dehydrogenase activity during temporary ischemia of the extremities

This prospective study depicts quantitative histophotometric characteristics of the changes in the histoenzymologic spectrum of the liver in the course of temporary ischemia of the extremities with subsequent revascularization. The increase in the activities of dehydrogenases under study in the course of a 3-hour ischemia, and the decrease of these parameters in 6- and 12-hour ischemia was discovered, that was determined as a compensatory response followed by the period of compensation exhaustion and the development of the period of complete exhaustion. The data of the study of drug correction of the postischemia syndrome confirmed the rationality of the efforts that were made. A special program developed for computer processing of histological data allows rapid adaptation of the methods for different histophotometric examinations with the use of TV analyzer of the picture, this creating wider possibilities as compared to the known analogs.     

Comparative characteristics of antigenic peculiarities and several other properties of stable long-term cultures of salmonella L-forms]

Enzymatic properties, sensitivity to antibiotics and peculiarities of the antigenic structure of stable L-forms of S. paratyphi B (L-115), S. typhimurium (L-71a-16) and S. typhi (L-5761) were studied. In difference from the initial strains, the L-form under study possessed a high penicillin and ampicillin sensitivity, and also a marked sensitivity to polymyxin and detergents; this characterized them as L-forms of protoplastic type. All the L-variants differed considerably by the enzymatic properties from the initial strains, and, in the majority of cases, retained the antigenic components and the species-specificity characteristic of the initial parental cultures. Despite the loss of the cell wall the synthesis of O-antigen in the L-forms under study was undisturbed. The 6-forms contained an antigenic component not found in the initial cultures and apparently causing the neutralizing activity of the L-antiser.     

The Effects of Weak Static Magnetic Field on the Development of Organotypic Tissue Culture in Rats

The effects of weak static magnetic field on the organotypic tissue culture of the rat cerebral cortex, liver, and spleen have been investigated. Exposure to a 200 μT static magnetic field induces tissue development, leading to the intensification of regeneration processes compared to the control explants.