[Tick-borne encephalitis with fulminant course and lethal outcome in patients after plural vaccination].

In the Kurgan region, the Siberian subtype of the tick-borne encephalitis virus (TBEV) is dominant. The vaccines prepared from Far-Eastern TBEV subtype are used in this area. Among TBE patients in 2007-2011, 23.79% were vaccinated according to complete or incomplete course. 76.9% of persons were vaccinated with Encevir vaccine, Tomsk. An unusual focal form of TBE with fulminant disease with lethal outcome was developed in a patient who was vaccinated 6 times with heterotype vaccines produced using the strains of the Far-Eastern TBE subtype. Inoculation of immunoglobulin in hospital produced aggravation of clinical symptoms, development of convulsions, brain oedema, and respiratory distress syndrome. The disease continues only 55 hours from first symptoms to fatal outcome. Siberian subtype of TBEV was isolated from patient spinal cord (Kurgan-118-2010 strain). Possible mechanisms of this disease are discussed.

[Morphological changes of brain choroid plexuses and ventricle induced by enterovirus infections in monkeys].

The morphological study of monkeys' brains, infected by the Bulgaria strain of enterovirus-71 (EV71), revealed specific for truncus cerebral encephalomyelitis, reactive and destructive changes in different areas of the brainstem and the spinal cord. For the first time viral cytopathology and destruction of choroid plexuses as an important secretory organ of the central nervous system, and ventricle of the brain infected by enterovirus have been studied. The specificity of this infection and the participation of neuroepithelium in reproduction of EV71 have been confirmed by identification of EV71 antigen in the choroid plexuses. According to our data the choroid plexuses take important part in the pathogenesis of EV71 encephalomyelitis. Pathologic changes have been found out in the barriers of CNS. The morphological changes in the brain of monkeys and cotton rats were similar; therefore the last one could be a useful model for different investigations.

[PRP(CJD) reproduction in the cerebral vascular plexus epitheliocytes in a new type of Creutzfeldt-Jakob disease].

The study of brain histological specimens from patients with Creutzfeldt-Jakob disease (CJD) revealed the active reproduction and accumulation of pathological prions in the epitheliocytes of cerebral vascular brain plexuses in a new variant of CJD. There was PrPCD accumulation on the cerebral ventricular ependymal cells and in the subpial superficial cortex parts of the cerebellum and brain to give rise to diffuse clusters, immature and kuru-plaques. Morphological changes in the blood-cerebrospinal fluid and cerebrospinal fluid-brain barriers are described and the possible pathways of intracerebral distribution of prions with cerebrospinal fluid considered.

[Morphological changes and prion accumulation in the cerebellar cortex in Creutzfeldt-Jacob disease].

Histological sections of the cerebellar cortex taken from 5 patients with Creutzfeldt-Jacob disease (CJD), including 3 patients with sporadic form, were comparatively studied. The rate of pathological alterations as well as localization of prion protein (PrP) deposits greatly varied in these two groups of patients. The intensity of neural loss, damage of glial cells and accumulation of PrP increased in parallel to the duration of the disease. In nvCJD, all layers of the cerebellum, the granular layer in particular, were affected to give rise to diffuse deposits of PrP and immature amyloid plaques. Vacuolization was less pronounced and occurred predominantly in the molecular layer in all patients.

[Prionic neuroinvasion and cerebellar lesion in Creutzfeldt-Jakob disease].

Examining the histological brain sections of patients with Creutzfeldt-Jakob disease (CJD) showed the accumulation of PrP(CJD) in the cerebellar cortical layers. In nCJD, the prion accumulated mainly in the granular layer in the area of synapses of moss fibers with granular cell dendrites in the cerebellar glomeruli and in the molecular layer in the area of the synapses formed by granular cell axons and great stellate neurons of the granular layer with the dendrites of Purkinje's piriform cells of busket cells and Golgi's cells. PrP(CJD) amyloid plaques were formed in these regions. In sporadic CJD, PrP(CJD) accumulated only in the cerebellar molecular layer in the area of the synapses formed by climbing fibers with the dendrites of Purkinje cells. The findings lead to the conclusion that prion spreads along different nerve fibers through the synapses. The preserved Purkinje cells contacting the plaques suggest that prion is not itself highly neurotoxic.

[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. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, in the past decades.

[Cytopathological changes in human and animal brain in prion diseases]. / Tsitopatologicheskie izmeneniia v mozge cheloveka i zhivotnykh pri prionnykh bolezniakh

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. The accumulation of phagocytes (microgliocytes, blood macrophages, pericytes) and emigration of lymphocytes from the blood vessels with diffuse infiltration of brain tissue and formation of aggregates around degenerating neurons, were noted.

[Effect of gentamycin on persistence of tick-borne encephalitis]. / Effekt gentamitsina pri persistentsii virusa kleshchevogo éntsefalita.

Effect of gentamicin, an aminoglycoside antibiotic, on the persistence of tick-borne encephalitis (TBE) virus in Syrian hamsters and Macaca iris in remote periods (70-434 days) after inoculation is studied. Attempts at virus isolation from animals treated with gentamicin failed. Unlike other aminoglycosides, e.g. streptomycin, gentamicin exerted no immunodepressive effect; moreover, immunocorrection was observed in some experiments on monkeys and hamsters. None of the 10 previously tested antibiotics elicited such an effect or inhibited the persisting TBE virus. Morphological study of the central nervous system in hamsters and monkeys showed that injection of gentamicin did not cause an exacerbation of chronic encephalitis. The mechanism of immunocorrecting effect of gentamicin is to be further investigated.

[Some mechanisms of the action of oligonucleotides: stimulation of the immune system and decreased infection of the brain in tickborne encephalitis]. / Nekotorye mekhanizmy deistviia oligonukleotidov: stimuliatsiia immunnoi sistemy i umen'shenie porazhenii golovnogo mozga pri kleshchevom éntsefalite.

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. Besides the stimulating effect, injection of ON to mice infected with TBE enhanced the destruction of lymphocytes and boosted the macrophagal activity, which was paralleled by a decrease in the intensity of virus-specific injuries in the brain. Thus, the antiviral activity of ON may be due to not only the fact that it is complementary to the TBE virus genome, but to stimulation of the immune system, specifically, the thymus and T-related elements, as well.

[The morphology of cell lines suitable for vaccine production studied by scanning electron microscopy]. / Issledovanie morfologii kletochnykh linii, prigodnykh dlia proizvodstva vaktsin, s pomoshch'iu rastrovoi élektronnoi mikroskopii.

Five nontumorogenic cell lines suitable for vaccine production were studied by SEM. It was shown that diploid cell line 41 originated from sheep embryo kidney and also two heteroploid cell lines, line 4921 originated from embryo skin and muscles of the African green young monkey and line 4647 from kidney of the adult monkey, maintained normal cell morphology and normal growth pattern in early and in later passages in cultures. Some alterations in epithelial dense monolayer formation were revealed in the heteroploid cell lines: in line 455 originated from spleen of the adult African green monkey, and in line 4184 originated from line 41. The revealed alterations can be considered as the early morphological signs of the transformation of epithelial cells in culture. These cell lines also retained the stability of their morphological characteristics at the earlier and later passages. All the studied cell lines were free of contaminating agents.

[Thymus involvement in the pathogenesis of experimental tick-borne encephalitis]. / Porazhenie timusa v patogeneze éksperimental'nogo kleshchego éntsefalita.

The involvement of the thymus in the infectious process was established in Syrian hamsters inoculated intracerebrally with tick-borne encephalitis (TBE) virus of different degrees of virulence. Active virus reproduction, amplification of virus antigen, massive evacuation of thymocytes, morphological lesions in the epithelial stroma and Hassall's bodies were observed. The lesions were more marked after inoculation of the highly virulent Sophyin strain. The unusually high plasmatization of lymph nodes adjacent to the thymus observed after inoculation with the low-virulent 41/65 strain is described. The results indicate that the involvement of the thymus is an important factor in the pathogenesis of TBE.

[Changes in the organs of the immune system of Syrian hamsters infected by the tick-borne encephalitis virus with various degrees of virulence]. / Izmeneniia v organakh immunnoi sistemy siriiskikh khomiachkov, zarazhennykh virusom kleshchevogo éntsefalita raznoi stepeni virulentnosti.

On the model of Syrian hamsters inoculated intracerebrally with 9 tick-borne encephalitis (TBE) virus strains varying in virulence, the specific involvement of the organs of the immune system (spleen and lymph nodes) was established and morphological features of the process described. The most severe destructive changes of these organs were found in the hamsters inoculated with highly virulent strains which appeared to be one of the factors leading to 100% death of the animals. In hamsters inoculated with strains of low virulence, the destructive changes in immunogenesis organs were less marked, but active migration and proliferative processes developed in them. The above-described differences in the involvement of the immune system organs should be taken into consideration in the interpretation of TBE pathogenesis and evaluation of the degree of virulence of the virus strains.

[Pathogenesis of persistent and chronic forms of tick-borne encephalitis (experimental study)]. / Patogenez persistentnoi i khronicheskoi form kleshchevogo éntsefalita (éksperimental'noe issledovanie).

A long-term experiment was conducted to study various aspects of the pathogenesis of persistent and chronic tick-borne encephalitis (TBE). Virological, serological, pathomorphological, electron microscopic and immunofluorescent techniques have been utilized in this study. Persistent TBE infection of Syrian hamsters examined over the period from 40 days to 2 years was characterized by the presence of virus-specific antigens in the organs and of specific antibodies in the blood serum. The persisting TBE virus was found to be predominantly localized in the central nervous system and spleen. Nerve cells underwent ultrastructural changes which were characteristic of flavivirus infection and related to the morphogenesis of viral particles. The authors have developed an experimental model of a primary progressive form of TBE with early and late manifestations of clinical symptoms of the disease.

[Characteristics of human-mouse hybrid cell lines and the changes induced in them by the poliomyelitis virus]. / Kharakteristika linii gibridnykh kletok chelovek-mysh' i izmenenii, vyzyvaemykh v nikh virusom poliomielita.

Cells of the four hybrid lines between continuous mouse cells Rag and human diploid embryonal fibroblasts were polymorphic and had mitotic activity in fully formed monolayers. Most of the these mitoses were pathological. Hybrid cells examined 8 months after hybridization were susceptible to the poliomyelitis virus infection with partial cytopathologic effect, they produced virus antigens and the infectious virus. Small hybrid cells displayed a more pronounced cytopathologic effect than did big, polynuclear and mitotic cells. Hybrid cells that were passaged 1.5 months after infection did not excrete any infectious poliovirus but contained poliovirus antigens.

[Cytotoxic activity of the serum of schizophrenic patients]. / Tsitotoksicheskaia aktivnost' syvorotki krovi bol'nykh shizofreniei.

The action of blood serum obtained from 38 schizophrenic patients and 28 control subjects was studied on new cells: Chinese hamster kidney, diploid human cells and glial cultures of immature ependymoblastoma of type 5 mice (IE-5) and neurinoma of rat trigeminal ganglion. Sera of schizophrenic patients--especially of those with a continuous course and disease standing over 5 years and with a recurrent course and disease standing less than 5 years--were found to be significantly more toxic. In the culture of IU-5, sera from schizophrenic patients of a younger age (the mean age 27 years) exerted the most pronounced cytolytic action. Toxic activity of the serum of schizophrenic patients persisted for 14 days at +4 degrees C and 60 days at -30 degrees C but was reduced following thermal treatment (+56 degrees C, 30 min).

[Streptomycin--an activator of persisting tick-borne encephalitis virus]. / Streptomitsin--aktivator persistiruiushchego virusa kleshchevogo éntsefalita.

The effect of streptomycin (C) on persistence of tick-borne encephalitis (TBE) virus in Syrian hamsters infected with 3 strains of the virus (41/65, Aina/1448, Vasilchenko ) intracerebrally or subcutaneously was studied. In the animals not given C the infectious virus could be detected in the brain for 8-14 days but not later although their organs (mostly brains and spleens) contained the hemagglutinating antigen and viral antigen detectable by immunofluorescence. Intramuscularly C was given twice daily for 13-35 days in a daily dose of 200 mg/kg. The C-treated hamsters yielded 7 virulent TBE virus strains: 3 from the brain, 3 from the spleen, and one from the blood. No virus could be isolated from the liver, kidneys, or lungs despite the use of various methods for isolation including tissue explantation. The activating effect of C was observed against the background of 4-fold decrease in the titre of complement-fixing and antihemagglutinating antibodies. C exerted its activating effect both at early (70 days) and late (9 months) stages of TBE virus persistence. The activating effect of C appears to be due to its immunosuppressive properties and neurotoxic action on the CNS.

[Effect of an alphavirus infection in pregnant mice on the susceptibility of their progeny to homologous infection in the postnatal period]. / Vliianie al'favirusnoi infektsii beremennykh myshei na vospriimchivost' potomstva k gomologichnoi infektsii v postnatal'nom periode.

Infection of random-bred mice with Sindbis virus at various intervals of pregnancy results in increased resistance of their offsprings to infection with this virus in the first days after birth. Antibodies present in the colostrum and milk of immunized females play an important role in decreasing the susceptibility of sucklings to alphavirus infection.

[Inhibiting effect of colcemid on the development of cytopathic changes due to the Sindbis virus]. / Ingibiruiushchee vliianie koltsemida na razvitie tsitopaticheskikh izmenenii, vyzvavaemykh virusom Sindbis.

The model of Chinese hamster (Cricetulus griseus) cell line infected with Sindbus virus was used to show that the presence in the maintenance medium of 0.01-0.1 micrograms/ml of colcemide inhibited the development of cytopathic changes, accumulation of viral antigens, and virus-specific complement-dependent cytolysis without affecting infectious virus production. The addition to the medium of 0.5% immune serum to Sindbis virus resulted not only in a similar inhibition but in a decrease of infectious virus titres. The latter effect was observed upon the addition of both colcemide and antiserum. Possible mechanisms of inhibition are discussed.