Biomedical subjects
Publications and source records attributed to L M Isachkova.
Stages of reproduction of a polyetiological model of coronary failure in rats are described. The model is based on the development of electrolyte steroid cardiopathy. Morphological studies confirmed the presence of degenerative changes in rat myocardium and coronary vessels. The model is intended for studies of the development and remission of cardiac diseases.
Ultrastructural changes in the population of pathogenic Yersinia pseudotuberculosis inhabiting a model soil ecosystem for a long time were studied. Changes in the bacteria were mainly adaptive until the 8th month of the experiment, their capacity to binary division was preserved. After 9 months cell structure changed: extracellular amorphous matrix appeared, probably due to increased mucus production.
Pathogenic properties of thermostable toxin responsible for pathogenicity of Yersinia pseudotuberculosis were experimentally studied. The toxin exerted a pronounced polyorgan cytopathogenic effect with predominating degenerative destructive changes and membranolytic effect on cell ultrastructure of parenchymatous organs. The toxin is believed to be directly involved in the development of typical pathomorphological picture of pseudotuberculosis, which confirms its pathogenetic role.
Seroepizootiologic surveys among wild rodents were carried out in Japan and Far East Russia in 1995 and 1996. Seropositive animals were only identified in Clethrionomys rufocanus (23/134) in Hokkaido, Japan. On the other hand, seropositives were identified in C. rufocanus (1/8), Apodemus agrarius (2/66), Apodemus spp. (2/26) and Microtus fortis (3/22) in Vladivostok, Far East Russia. Total RNA was isolated from lungs of seropositive animals and the S genome segments were amplified by PCR, cloned and sequenced. The S and M genomes of hantavirus, derived from Japanese C. rufocanus (Tobetsu genotype), were most closely related with Puumala viruses (76-79% nucleotide and 95% amino acid identities for S genome, 70-78% nucleotide and 87-92% amino acid identities for M genome). The recombinant nucleocapsid protein of Tobetsu genotype was antigenically quite similar with that of Sotkamo. These suggest that the virus endemic in Japanese C. rufocanus belongs to Puumala virus. Phylogenetic analysis indicates that the genotype forms a distinct lineage within Puumala viruses. Partial S segment (1-1251 nt), derived from seropositive M. fortis in Vladivostok, was sequenced and analyzed. The S genome segment, which was designated Vladivostok genotype, was most closely related with Khabarovsk virus (79% nucleotide and 90% amino acid identities) which was isolated from M. fortis.
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The study of pathology in pseudotuberculosis has showed that clinical and morphological nature of the disease is related to granulomatous inflammation in organs and tissues. The authors have established that a relapsing course of this infection may be due to pronounced specific sensitization of the body when granulomas appear in large numbers. Morphogenesis of acute granulomatous inflammation in pseudotuberculosis reflects a consecutive involvement of cellular reactions of the immediate and delayed hypersensitivity. In the authors' opinion pseudotuberculosis granulomas may be assigned to immune hypersensitive granulomas of mixed type according to the classification suggested by A. I. Strukov and O. Ya. Kaufman. The data obtained allow a hypothesis that granulomas tending to cause a purulent liquefaction and necrosis, like pseudo-tuberculous granulomas, could be considered as a morphological sign of granulocytic-macrophagal immune deficiency.
Materials characterizing the antiviral activity of Mytilane, manifested by the protection of 50-60% of mice infected with the lethal dose of influenza virus and by a decrease in the severity of pathological changes in the lungs of mice, are presented. The inhibiting activity of Mytilane with respect to the reproduction of influenza virus in vivo and in vitro under experimental conditions is demonstrated.
Surgical material from 55 children, from 2 to 15 years of age with an abdominal form of pseudotuberculosis (appendix, lymph nodes, ileum) and the immunogenesis organs (lymphoid tissue of the small intestine, lymph nodes, appendix, spleen and thymus) of 277 rabbits infected with virulent strains of the Yersinia pseudotuberculosis I serovar at the dose of 10(8) bacterial bodies were investigated. The results testify to the disturbance of all parts of the immuno-phagocytic system in pseudotuberculosis with the development in some cases of secondary immunodeficiency due to the specific damage of the lymphoid tissue and the functional deficiency of phagocytes. This probably results from the cytotoxicity of the pathogenic factor inhibiting the host defense mechanisms. The tendency to pseudotuberculosis exacerbation and recurrence is associated with the development of the immunodeficiency.
Experimental studies on guinea pigs have shown that Y. pseudotuberculosis lipopolysaccharide is capable of inducing endotoxinemia accompanied by the development of the thrombohemorrhagic syndrome. In cases of pseudotuberculosis the importance of the increased synthesis of prostaglandins and cyclic nucleotides with the prevalence of PGF2 alpha and cGMP in the genesis of toxico-allergic manifestations of pathologic processes has been established. The pathomorphological picture of pseudotuberculosis endotoxinemia is characterized by sludge, the vascular thrombosis of the microcirculatory bed, diapedetic hemorrhages, delymphatization of the immunogenetic organs. The moderately pronounced action of indomethacin, a prostaglandin inhibitor, on the manifestations of pseudotuberculosis endotoxinemia has been revealed.
A new pathogenetic pattern of pseudotuberculosis has been derived on the basis of original clinical, anatomical and experimental findings as well as literature data. Careful consideration is given to: a basic mode of infection (alimentary), emergence of the primary affection with a rapid blood invasion by the agent (primary bacteremia), development of specific sensitization, multiorgan secondary focal impairment with lymphogenic dissemination of the infective agent (specific pseudotuberculous polyadenitis), formation of secondary immunodeficiency, consequent repeat bacteremias, recurrences, symptoms of infectious process aggravations, immunological rearrangement with dominating delayed hypersensitivity. As a rule, the disease terminated by elimination of the secondary foci and recovery.
The functional activity of polymorphonuclear leukocytes (PNL) of the peripheral blood of rabbits infected orally with Y. pseudotuberculosis was studied. By day 5 of Y. pseudotuberculosis infection the pronounced stimulation of the myeloperoxidase system with the appearance of respiratory explosion was registered with the use of the nitro blue tetrazolium (NBT) test. The NBT-positive leukocyte index was found to increase 3.32-fold in comparison with the initial data. According to the results of the liposomal cationic test, the stimulation of the system of nonenzymatic cationic PNL proteins was revealed. By day 12 after infection the median cytochemical coefficient reached 2.035 +/- 0.005 conventional units, while in intact animals it was equal to 0.995 +/- 0.002 units. By day 20 a repeated, not so great, increase in the amount of NBT-positive PNL and in the content of cationic proteins in them was observed. The data thus obtained are indicative of the faintly pronounced secretory degranulation of PNL, which was probably one of the causes responsible for disturbances in the process of the digestion of Y. pseudotuberculosis by leukocytes, while their capacity for ingestion was retained.
A pronounced affinity of Yersinia pseudotuberculosis to the epithelium of renal tubules has been first stated. Microorganisms disseminate through blood into the renal tissue and enter the winding tubule lumen as part of glomerular filtrate. Due to invasion and intensive multiplication of Yersinia pseudotuberculosis within epitheliocytes the epithelium is damaged and necrotic nephrosis develops. Intensive microbial colonization was noted in the tubule lumen. Extra-capillary glomerulonephritis due to Yersinia pseudotuberculosis was detected for the first time. Our data can account for long-term renal disorders in patients with pseudotuberculosis.
Some data showing specific ways of interaction of Yersinia pseudotuberculosis with the epithelium of the small intestinal mucosa have been received for the first time by using light microscopy of semithin sections. Comparative study of the lesion of the epithelium of different parts of rabbit small intestine by oral inoculation with Yersinia tuberculosis has expanded the ideas of the infection entry. It has been established for the first time that the most intensive penetration of the microorganisms into the epithelium of the mucous membrane takes place in the duodenum and jejunum. As the infected contents is evacuated via the intestinal tract, the Yersinia pathogenicity decreases, and in the ileum, the invasion of the microorganisms becomes less pronounced. It has been revealed that in pseudotuberculosis, there takes place a repeated dissemination of the infection in the intestinal tract because of decay of the involved enterocytes, which is of pathogenetic importance for the progress and outcome of the infection.
Experimental pseudotuberculosis arthritis was reproduced by means of antigenic irritation of the knee joint in the presence of specific sensibilization. Pathomorphology is characteristic of the acute exudative-proliferative synovitis and periarthritis. The results obtained allow one to draw the conclusion on the infectious-allergic genesis of the joint involvement in pseudotuberculosis. The stages in the allergic responses of the synovial membrane with subsequent development of early and late immune inflammation are revealed.
The study of the action of Y. pseudotuberculosis introduced into the cavity of the ligated intestinal loop of a rabbit, into the stomach of 2- to 4-day-old suckling mice or injected intradermally has made it possible to establish the importance of the invasive and toxic activity of this microbe in the pathogenesis of pseudotuberculosis infection. The lesion of the small intestine develops due to the penetration of the bacteria into the mucous membrane and the combined action of the microbial cells inhabiting the stroma, and secreting into the environment of cytotoxins, toxic substances with an enterotropic action or enterotoxins and factors increasing the permeability of the vessels. Y. pseudotuberculosis strains with high and low invasiveness have been isolated.
A comparative study of the experimental infection of monkeys caused by brain P-40 of Powassan virus isolated in the Primorye Territory of the USSR and by the prototype Canadian strain LB was carried out. Powassan virus was found to be pathogenic for Macaca rhesus. Clinical and pathomorphological picture of the experimental encephalitis was studied. Full identity of the infection caused in the monkeys by the strain P-40 and the Canadian strain LB of Powassan virus has been proved. On electronmicroscopic examination of the central nervous system the virus was detected in the neurons, glial cells and intercellular spaces. The virions of the strains studied have identical morphological parameters, being 37 to 45 nm in diameter and having spherical shape. The data obtained point to a marked neurotropism of the virus. They will contribute to elucidation of the virus role in the infectious pathology of man, and namely, in verification of encephalitis cases not associated etiologically with the virus of the spring-summer tick-borne encephalitis.
Brains of adult white mice inoculated with the P-40 strain of Powassan virus isolated in Primorsky Krai (U.S.S.R) from ticks were studied by light and electron microscopy. Accumulations of virus particles were found in neurons and their dendrites and axons, in glial cells, and in intercellular spaces. In the nerve cells, most prevalent were changes of the type of chromatolysis and formation of small vacuoles, associated with the alteration of the endoplasmic reticulum induced by virus morphogenesis. In virus-affected cells, multilayer dense membranes were found.