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Spongiform encephalopathies may be transmitted to people and to laboratory animals by an unusual infectious agent tentatively called a prion. These encephalopathies include Creutzfeldt-Jakob disease, kuru, and Gerstmann-Straussler-Scheinker syndrome in humans, as well as scrapie in sheep. The prion may be composed predominantly of a protein called, simply, prion protein. It has become clear that the prion protein associated with the infectious disease is very closely related to a normal protein which occurs naturally in all brain tissue. The normal gene is designated PrP27-30; the activity of this gene is the same in both healthy brains and brains infected with some form of spongiform encephalopathy. It is striking that the PrP27-30 gene seems to be very similar in mice, hamsters, and people, which are species not otherwise closely related. To learn more about the role of prion protein in both normal and infected brain tissue, antibodies were prepared which react with this protein. Once the antibodies were prepared, they were then used to immunohistochemically identify the location of prion protein within brain tissues. In this technique, the antibodies are allowed to bind to prion protein present in microscopic sections. Chemical reactions are then used to indicate the presence of the antibodies. Therefore, when the section of brain tissue is viewed under the microscope, the colored areas indicate the location of the prion protein. Using this method, it was found that the prion protein is located within the cytoplasm of the brain cells of both normal and infected brains. Since other research has indicated that prion protein is associated with membrane structures, this suggests that the prion protein is most likely associated with the endoplasmic reticulum, an important membrane structure within cells. Immunohistochemical localization also showed that prion protein was present in the amyloid plaques of laboratory mice with scrapie and humans with either kuru or Creutzfeldt-Jakob disease. The structureless amyloid plaques in the brain are also a characteristic pathological feature of Alzheimer's disease. However, when the same method was used on a microscopic section of an Alzheimer's disease patient's brain, the amyloid plaques did not stain, indicating that prion protein may not be present in the amyloid plaques of this disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Creutzfeldt-Jakob disease and similar diseases, collectively called spongiform encephalopathies due to the spongy appearance of affected brain tissue under the microscope, are caused by infectious agents which do not resemble conventional bacteria or viruses. Some investigators simply call them unconventional agents, while others have coined the term 'prion' to describe this unique type of infectious agent. Most of the research on prions is conducted on scrapie, a disease of sheep which is easily adapted to laboratory animals but is not thought to infect people. It has been established that the brains of infected animals slowly fill with infectious prions, although prions have never been seen and no one is sure what a prion would look like. It is also known that a large amount of prion protein accumulates in the brain at the same time. It seems reasonable to suppose that prion protein is the main component of which prions are built, but this is far from certain. To gain more insight into whether prions are actually constructed of prion protein, experiments were performed using agarose isoelectric focusing. The technique is sophisticated, but the basic principle is to separate charged molecules in an electric field. When the various components of a complex mixture are separated, components found close together have similar charge properties. In these experiments, the infectious prions, which can be identified only by their ability to make hamsters sick, were found in the same location as the prion protein. This observation is important; if an infectious prion contained many other proteins besides the prion protein, the chance that it would have the same electrical charge properties as the prion protein would be very small indeed. These experiments lend credence, therefore, to the notion that the prion protein is the primary building block of the actual infectious prion itself. (Consumer Summary produced by Reliance Medical Information, Inc.)

A prion is an unusual infectious agent. In fact, it is easier to say what it is not, rather than what it is. Prions are not like any known bacteria or virus, and if they contain any genetic material at all it has not yet been scientifically detected. Several human diseases appear to be caused by prions; the most common is Creutzfeldt-Jakob disease, which is quite rare. Since it can kill scientists as well as patients, it is not surprising that much of the research on prions is actually conducted on scrapie, a prion disease of sheep which is easily adapted to laboratory animals. The development of scrapie in an animal is correlated with the appearance of prion protein within the brain; little is known, however, about the precise role of this protein in the structure of the actual infectious agent. A study was conducted of hamster brains infected with scrapie to learn more about the distribution of the prion protein within the brain and about its physical and chemical properties. Such a study is conducted using fractionation. When the infected brain is homogenized, the resulting soupy mix contains many different components. When these components are fractionated (that is, separated), both the prion protein and the infectious prions are found with the fragments of cellular membranes. Just as oil and water do not mix, it is possible to separate the 'oily' lipid components of membranes from those which are more soluble in water. When this is done, the prion protein and the infectious prions seem to remain in the portion which is not soluble in water. While the actual structure of the infectious prion remains unknown, these studies confirm that the so-called prions seem to be a part of the membrane structures of cells. (Consumer Summary produced by Reliance Medical Information, Inc.)

This in vitro study compared the shear bond strength of a resin-modified glass-ionomer restorative material (Fuji II LC) bonded to saliva-contaminated dentin versus noncontaminated dentin. Seventy-five extracted human molar teeth were randomly divided into five groups of 15 samples each. The dentin was treated with 10% polyacrylic acid for 20 seconds, rinsed, and dried. The acid-treated dentin surfaces in Groups 1-4 were contaminated with saliva. In Group 1, the saliva was air thinned. In Groups 2-4, saliva was dried completely with compressed air. The saliva-contaminated dentin in Group 3 was rinsed and dried. The saliva-contaminated dentin in Group 4 was rinsed, dried, treated with 10% polyacrylic acid, and dried. Specimens in Group 5 received no contamination. The resin-modified glass-ionomer cement restorative material was mixed and applied to the dentin surfaces. Following placement of the restorative material and 7 days of storage, the specimens were thermocycled 300 times. Using the Instron Universal Testing Machine, a shear force was applied to the restorative material. Shear bond strength values were compared among the groups using a one-way ANOVA and Student-Neuman-Keuls Multiple Range Test (α = 0.05). The noncontaminated specimens (Group 5) were significantly stronger than the contaminated specimens (Groups 1-4). There were no significant differences in bond strength among the groups containing contaminated specimens. Salivary contamination occurring after dentin etching significantly reduced the bond strength of the resin-modified glass-ionomer restorative material to dentin. Neither rinsing nor rinsing and re-etching resulted in bond strengths as great as to noncontaminated dentin. [ABSTRACT FROM AUTHOR]

The extraction and purification of gangliosides from brains of animals infected with the scrapie agent was evaluated by scaling-down a large-scale procedure currently used with bovine brains. Inactivation experiments employed hamster brains infected with the 263 K strain of scrapie. Residual infectivity was determined at different points of the procedure and in the final preparation by an in vivo animal bioassay. The efficacy of single steps, which included chemicals or physical techniques known to affect the viability of the scrapie agent, was verified by spiking experiments where known amounts of infectivity were added just before each single step. Infectivity was significantly diminished at early stages of the purification, and no infectivity was detected in the final preparation containing purified gangliosides. The significant reduction of infectivity at intermediate steps and the total absence of detectable infectivity in the final product confirmed that a combination of heat and exposure to sodium hydroxide, even in the presence of organic solvents, completely inactivated the scrapie agent. [ABSTRACT FROM AUTHOR]