[Prion diseases at the present stage and the investigations conducted at the M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences].

The review deals with the basic characteristics of prion diseases of man and animals. It details the studies of some little known aspects of the pathogenesis of prion diseases and their lifetime diagnosis, conducted at the M. P.

Cytopathological changes in human and animals brains in prion diseases.

Studies of histological preparations of the brains of humans and animals with prion diseases showed that neuron vacuolization often starts and develops intensely in the distal segments of dendrites. Two types of neuron body death were noted - cytolysis and pyknosis, the latter usually being associated with vacuolization of dendrites. The involvement of the main types of neuroglia in the pathogenesis of prion diseases was established, which provides grounds for referring to gliosis rather than astrocytosis.

[Gliosis as a trigger of pathomorphological changes in prion diseases].

Experiments with three cell lines revealed that the scraplecontaining cerebral extract, obtained from preliminarily infected 6-month mice, sharply induced the cellular proliferation, which was registered yet in 3 days after incubation. However, the cerebral extract of healthy 6-month mice did not virtually influence the velocity of cells' reproduction in all three cultures. The authors suggest, with respect to published data and to their independently found research results, that the gliosis of primary importance in shaping up the pathomorphological alterations in the cerebral tissue in prion diseases of man and animal.

[Cytopathological changes in human and animal brain in prion diseases].

The study of brain histological sections of humans and animals afflicted by prion diseases has shown that neuronal vacuolization began in and intensely spread from the distal portions of dendrites. Two types of neuronal cell body death were demonstrated, including cytolysis and pyknosis, the latter being usually associated with dendrite vacuolization. The involvement of major glial types in the pathogenesis of prion diseases was established, which argues against the concept of astrocytosis in favor glyosis.

[In vivo diagnosis of Creutzfeldt-Jakob disease].

The paper presents the data concerning usage of some original method of vital laboratory diagnostics of Creutzfeldt-Jacob disease that belongs to the group of prionic diseases. The method consisted in the inoculation of inoculative culture of rat Gasser ganglion's neurinoma by biologic materials investigated (serum and clot of blood) with the following passivation and investigation of the contaminated culture by means of both morphologic and electron microscopic methods. As an example of vital verificated case the wide pathomorphologic analysis of the biopsy sample of brain was presented.

[Some mechanisms of the action of oligonucleotides: stimulation of the immune system and decreased infection of the brain in tickborne encephalitis].

Morphological changes in the thymus, spleen, and brain are analyzed in white mice injected 16-component oligonucleotide (ON) pE16 complementary to the NS3 protein gene sequences of tickborne encephalitis (TBE) virus in doses of 1 to 0.001 nM. ON stimulated thymic and splenic cells.

[Experimental latency of scrapie].

BALB/c mice infected with the scrapie agent without apparent symptoms of the disease for 12 to 14 months after inoculation were examined by virological and histological methods. Changes in the central nervous system characteristic of the pathohistological picture of scrapie were detected in two out of 66 mice. Intracerebral challenge of mice with the examined material from these animals did not result in disease.

[Lifetime diagnosis of prion transmissive encephalopathies].

An original method for life-time diagnosis of Greutzfeldt-Jakob's disease, a neurodegenerative disease belonging to transmissive spongiform encephalopathies, is proposed. It consists in inoculation of the examined biological materials (blood serum and clot) into a continuous culture of the rat Gasser's node neurinoma, followed by passages and study of the inoculated culture by morphological methods and electron microscopy.

[The Gerstmann-Sträussler syndrome: new diagnostic possibilities].

On the basis of clinical picture of the disease, data of CT, MRT, psychological study, original laboratory investigation aimed at indication of changes in transposed neuroglia cells induced by the causal agent of subacute spongious transmissible encephalopathies, the diagnosis of patient K., 49 years old, was considered to be: syndrome of Gertsmann-Sträussler [correction of Herstmann Streussler]. Duration of the disease was 2 years.

[Antiviral effect of various oligonucleotide derivatives, complementary to tick-born encephalitis virus RNA].

Antiviral effect of two nucleotides complementary to tick-borne encephalitis (TBE) virus genome and their derivatives was compared to that of noncomplementary oligonucleotides. All the tested reagents influenced TBE multiplication in cell culture, this manifesting by various degrees of suppression of the cytopathic effect of the virus. Intact oligonucleotides, both complementary and noncomplementary to TBE, reduced virus titer by 2-4 orders, whatever the concentration of oligonucleotide.

[The antiviral action of medicinal plant extracts in experimental tick-borne encephalitis].

Some mechanisms of inducing resistance to experimental infection with tick-borne encephalitis virus were studied in experimental mice treated with aqueous extracts of berries of Vaccinium vitis-idaea, black currant, Vaccinium myrtillus, and of greater celandine grass. The condition of the immune system organs (spleen and thymus) after treatment with the extracts under study was analysed. A correlation was found between the degree of developing resistance to infection, virus accumulation in the brain, blood, spleen and thymus and changes in some parameters (spleen and thymus indices) of these immunocompetent organs.

[The interrelationship of the causative agents of subacute transmissible spongiform encephalopathies].

Virological, histological, and electron microscopy methods were used to study the features of the infectious process in minks infected with scrapie agent as compared with that in minks infected with the agent of mink transmissive encephalopathy and in mice infected with scrapie. The results of the study showed the similarity in the clinical picture and the pattern of histological and ultramicroscopic lesions in minks infected with either of the agents. On the basis of the authors' own data and those from the literature, the relationship among the agents of the diseases comprising the group of subacute transmissive spongiform encephalopathies is discussed.

Development of antibodies to axonal neurofilaments in the progression of chronic tick-borne encephalitis.

We followed the presence of autoantibodies to neurofilaments (NF) in the sera of patients with acute tick-borne encephalitis (TBE), chronic TBE, amyotrophic lateral sclerosis (ALS), and other diseases of CNS. The diagnosis was made according to clinical signs and based on virus neutralizing antibodies. Autoantibodies to NF were found in the majority of chronic TBE patients during disease progression, but were neither present in acute TBE nor in chronic TBE cases during the stabilization phase.

[Experimental phytotherapy of tick-borne encephalitis].

The virucidal effect of aqueous extracts of a number of plants was studied in tick-borne encephalitis (TBE) virus titration in SPEV cell culture in microplates, as well as their capacity to induce resistance in virus-infected mice. The aqueous extracts of ledum, motherwort, celandine, black currant, cowberry and bilberry inactivated TBE virus practically completely, and those of St. John's wort, pot marigold, tansy, chamomile, milfoil, and inula only partially.

[Antibodies to the structural elements of the neuron in patients with amyotrophic lateral sclerosis and in their healthy relatives].

The results of determining antibodies to the structural elements of neuron in the serum and CSF of 100 patients with lateral amyotrophic sclerosis (LAS), in the serum of their relatives (n-67), and in biological fluids of 50 patients suffering from other neurologic diseases allowed the following conclusions to be made. The predominance of antibody demonstration in the CSF of LAS patients over that in the serum may attest to the immune response on the part of the CNS. The presence of antibodies in the relatives (not-blood ones for the most part) of LAS patients suggests an infectious nature of the disease.

Alterations of arginase activity in scrapie-infected mice and in amyotrophic lateral sclerosis.

We followed the dynamics of arginase activity, the ultrastructural changes, and accumulation of the scrapie agent in the CNS of scrapie-infected mice. The arginase activity has been shown to increase 5-fold within the first 3-4 months of the incubation period followed by subsequent fall at its end. The peak of increased arginase activity coincided with appearance of multilayer membranes, whereas the decrease of this activity was associated with the greatest development of status spongiosus, synaptic degeneration, accumulation of five-layer membranes as well as with maximal accumulation of the scrapie agent in the CNS.

[Cytomorphologic study of a line of hybrid somatic cells persistently infected with the scrapie agent].

Virological, cytological and electron microscopic methods were used to study the peculiarities of the scrapie agent persistence in the tissue culture of the mouse and human hybrid cells. A long-term persistence of the scrapie agents in the cells (658 days) has been obtained. The fact of persistence is confirmed by the results of biotest and electron microscopic studies of the mouse CNS.

[Anti-neurofilament antibodies in slow infections of the nervous system].

Twenty-six patients including 12 with lateral amyotrophic sclerosis, 7 with multiple sclerosis, 5 with the Creutzfeld-Jakob disease and 2 with Alzheimer's disease were examined. Antibodies to neurofilaments in the blood serum were detected in all cases of the Creutzfeld-Jakob disease and Alzheimer's disease and in 8 patients with lateral amyotrophic sclerosis with clinical evidence of supranuclear structure involvement. A conclusion is drawn about a certain similarity of pathogenic mechanisms of these diseases, as well as about heterogeneity of the cytoskeleton of neurons in the brain and the spinal cord.

Persistence of the scrapie agent in glial cells from rat Gasserian ganglion.

Persistence of the scrapie agent in glial cell monolayers from rat Gasserian ganglion have been studied by electron microscopy, virologic and histologic methods. Under chosen experimental conditions the scrapie agent had been shown to persist in cells for over 2 years. The infected cells appeared to be infectious for BALB/c mice throughout.

[Clinico-morphological study of transmissible encephalopathy of mink].

Histological examination of the central nervous system of naturally infected and dying minks revealed the picture of "status spongiosus" in the brains and spinal cords, lysis and loss of neurons, hypertrophy and proliferation of astroglia typical of transmissible mink encephalopathy (TME). The disease in minks was induced experimentally by oral, suboccipital, intramuscular, intraperitoneal, and subcutaneous routes of inoculation inducing typical clinical signs and histological lesions. Suspensions prepared from the infectious material obtained from the Institute of Poliomyelitis and Viral Encephalitides, Acad.