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Biomedical subjects

A L Gintsburg

Publications and source records attributed to A L Gintsburg.

At least 73 records · Page 4Linked to original sources
PubMedDate not supplied

[The current status and outlook for molecular genetic methods in solving the tasks of medical microbiology].

The article deals with modern methods, viz. PCR, molecular display and genotherapy, which permit the new approach to the solution of problems connected with the identification of infective agents, the study of the mechanisms of the pathogenesis of infectious diseases and their treatment. In this article concrete examples, clearly demonstrating how each of the above-mentioned technologies makes it possible to broaden the circle of problems solved in infectious pathology of man, are presented.

Genetic Techniques↗
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[The mechanism of action and the nature of the factors inducing the formation of uncultivatable forms of Salmonella typhimurium].

Approaches to the study of gene expression in the process of transition and prolonged stay of bacterial cells in the uncultivated state have been worked out with the use of the methods of reverse transcription and polymerase chain reaction. The differential expression of genes pqi and stn has been shown to occur in the uncultivated forms of S. typhimurium. The factor inducing the process of the transition of Salmonella cells into the uncultivated state has been found out.

Base Sequence↗
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[Comparative evaluation of the efficacy of Borrelia indication in ixodes ticks (Ixodidae) using dark field microscopy and polymerase chain reaction (PCR)].

Indication of Borrelia (B. burgdorferi sensu lato) in 205 adult unfed I. persulcatus ticks from a natural focus was carried out simultaneously by methods of PCR and dark-field microscopy of vital preparations. PCR method revealed Borrelia prevalence in considerable number of ticks, in which Borrelia were not found by microscopy of 250 microscopic fields in a preparation from each individual tick. At the same time, PCR method didn't give positive results for approximately 8% of ticks, which contained rather high concentration of Borrelia (more than 10 per 100 microscopic fields). In general, PCR method doesn't have advantages in comparison with a microscopy of vital preparations for study the Borrelia prevalence in ticks.

Animals↗
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[Ecological-genetic mechanisms of the transition of Salmonella typhimurium to the dormant state in the environment].

The dynamics of vegetative and dormant (noncultivable) of S. typhimurium cells of two isogenic strains in association with microalgae Scenedesmus quadricauda and under the action of the exometabolites of the algae at different stages of their growth was studied using in parallel bacteriological method and PCR. The study revealed that at the stage of active growth green algae and their metabolic products maintain the survival of salmonellae (strain TR = 1) vegetative forms in water at an optimum temperature. Low temperatures induced their gradual (3 weeks) transition to the dormant state. The exometabolites of old dying algae induced the rapid (several hours) and complete transition of the bacterial population (TR = 1) to noncultivable state. In our experiments the insertional mutation in gene pqi (strain PhoA = 8), inducing the defect of transmembrane protein and disturbances in the transition of salmonellae to dormant state, led to stable existence (lasting 7 months, i.e. the whole term of observation) of vegetative cells. The natural inducers tried in our experiments did not lead to the formation of the dormant forms of salmonellae in this mutant strain.

Acclimatization↗
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[Problem of bioterrorism under modern conditions].

It is practically impossible to discuss the problem of bioterrorism (BT) and to develop effective programs of decreasing the losses and expenses suffered by the society from the BT acts without evaluation of the threat and prognosis of consequences based on research and empiric data. Stained international situation following the act of terrorism (attack on the USA) on September 11, 2001, makes the scenarios of the bacterial weapon use (the causative agents of plague, smallpox, anthrax, etc.) by international terrorists most probable. In this connection studies on the analysis and prognostication of the consequences of BT, including mathematical and computer modelling, are necessary. The authors present the results of initiative studies on the analysis and prognostication of the consequences of the hypothetical act of BT with the use of the smallpox causative agent in a city with the population of about 1,000,000 inhabitants. The analytical prognostic studies on the operative analysis and prognostication of the consequences of the BT act with the use of the smallpox causative agent has demonstrated that the mathematical (computer) model of the epidemic outbreak of smallpox is an effective instrument of calculation studies. Prognostic evaluations of the consequences of the act of BT under the conditions of different reaction of public health services (time of detection, interventions) have been obtained with the use of modelling. In addition, the computer model is necessary for training health specialists to react adequately to the acts of BT with the use of different kinds of bacteriological weapons.

Bioterrorism↗
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[Influence of tumor necrosis factor on the growth of vegetative and nonculturable forms of Salmonella].

The growth rate of the vegetative forms and the recultivation rate of the uncultivable forms of Salmonella isogenous strains, one of these strains carrying mutation in gene pqi, were studied. The multiplication rate of the vegetative and uncultivable forms of Salmonella control strain in the spleen of infected animals at the initial stages of the infectious process was shown (in vivo) to be considerably accelerated after the preliminary incubation of the culture with cytokine (tumor necrosis factor). The multiplication rate, in vivo and in vitro, of Salmonella vegetative and uncultivable forms with mutation in gene pqi did not change after the incubation of the cells with cytokine, which is indicative of an important role played by the product of this gene in the process of the interaction of bacteria with cytokines. The full nucleotide sequence Salmonella gene pqi was determined.

Amino Acid Sequence↗
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[Integrative processes in modern epidemiology].

The integration of achievements in population ecology and the molecular genetics of pathogenic microorganisms into nowadays epidemiology of infectious diseases and the formation of its corresponding trends are discussed. The decisive role of highly complicated key problems of general epidemiology, such as the regularities of the autochthonous existence of pathogenic bacteria in the environment, the mechanisms of the pathogenicity regulation of infective agents and the formation of their epidemic variants, the mechanisms of the prolonged reservation of pathogenic bacteria at interepidemic (interepizootic) periods, the mechanisms of transformation of active (vegetative) and dormant forms in bacterial populations at different stages of epidemic and epizootic cycles, is demonstrated. The detection and analysis of such processes, and especially their latent mechanisms, become possible with the use of new concepts and methodological approaches, highly productive for the progress of epidemiology.

Adaptation, Physiological↗
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[Mechanisms of activation of pathogenic bacteria in the host organism].

A minireview of the data of literature on the interaction of bacteria with cytokins and the stimulation of the growth of pathogenic bacteria by some cytokins is presented. The addition of tumor necrosis factor-alpha into the culture medium has been shown to stimulate the growth of Salmonella virulent and avirulent strains 4-fold and 2-fold respectively. This cytokin has also been shown to produce a stimulating effect on the process of the in vitro and in vivo recultivation of noncultivating forms of virulent and avirulent strains.

Animals↗
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[Differential activity of genes of Mycoplasma pneumoniae in acute and chronic forms of experimental infection].

The complex of investigations was carried out with a view to study the mechanisms making it possible for mycoplasmas to switch off the expression of definite genes in persistence. The main method used in these investigations was the method of molecular portrayal, or RNA fingerprinting, with the use of arbitrary primers. The comparative analysis of gene expression in M. pneumoniae strains having different virulence revealed that in the avirulent strain subcultured under in vitro conditions the expression of considerable number of genes was inhibited. In the body of an experimental animal the expression of many genes, including the gene coding the synthesis of the main pathogenicity factor, adhesion protein, switched on.

Acute Disease↗
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[Creation of a controlled model of respiratory mycoplasmosis].

To create the controlled model of respiratory mecoplasmosis, laboratory animals with induced immunodefeciency were infected with M. pneumoniae strain having different degrees of virulence. Immunodeficient state was induced in susceptible animals (hamsters) by the injection of cyclophosphamide. The infection of immunodeficient animals with a virulent strain induced the development of severe manifest pneumonia with 50% mortality rate. The infection of the animals with induced immunodeficiency with the avirulent strain attenuated in the process of 10-year subculturing in acellular media led to the development of moderate pneumonia characterized by the proliferation of the infective agent in pulmonary tissues and the presence of pathomorphological changes. The simultaneous infection of control hamsters with the same strain did not induce the development of infection. The infection of the experimental animals with the avirulent strain in the presence of induced immunodeficiency resulted in the partial restoration of the virulent properties of the strain, which was manifested by the activation of the capacity of the infective agent for colonization and proliferation in body tissues of the animals.

Animals↗
PubMedDate not supplied

[Influence of environmental factors on the expression of Mycoplasma pneumoniae gene responsible for the synthesis of protein P1 adhesion].

The effect of different physical and chemical factors on the process of transition of persisting mycoplasmas into active virulent state was studied to find out conditions promoting the development of acute infection in the course of chronic infection. The activity of the gene coding the synthesis of protein P1, the main pathogenicity factor, was evaluated in the reverse transcriptase test--PCR under conditions of heat and cold shocks, oxidation stress, varying osmotic pressure. An increased osmotic pressure, heat and cold shocks were shown to induce the transcription activation of the gene coding the synthesis of P1 in the avirulent strain, and consequent restoration of its adhesive properties indicative of virulence. M. pneumoniae avirulent strain was characterized by greater resistance to oxidation stress and to a rise in osmotic pressure, this property requiring further study. Quite probably, M. pneumoniae DNA-binding proteins earlier detected in persisting and avirulent cultures by taking part in the compactization of DNA contribute to the adaptation of mycoplasmas to different stress influences. There are grounds to suggest that M. pneumoniae possess mechanisms regulating the expression of genes, in particular the gene coding the main pathogenicity factor, under the influence of different environmental factors.

Adhesins, Bacterial↗
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["Quorum sensing" or social behavior of bacteria].

The review deals with the data of literature on the role of the "quorum sensing" (QS) system ensuring the social behavior of bacteria in the regulation of virulence genes. The mechanisms of the action of these systems in Gram-negative and Gram-positive bacteria, as well as the influence of acyl-homoserine lactones, one of the components of the QS system, on the immune response of the infected host are discussed. In addition, in this review the data of literature on the existence of bacteria in the form of biofilms are presented. The methods of the identification of biofilms, the methods of their experimental preparation and the role of the QS system in the process of their formation are considered.

Bacteria↗
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[Development of the controlled model of persisting infection , caused by Pseudomonas aeruginosa and bacteria of the complex Burkholderia cepacia].

As the result of testing three different variants, the experimental models of persisting infection for P. aeruginosa and B. cepacia have been developed. These doses differ in the time of administration, doses of antibiotics and the infective doses of the microorganisms. The administration of the sub-inhibiting concentration of antibiotics for 5 days and the subsequent infection of laboratory animals (non-inbred mice) B. cepacia strains in a dose of LD50 leads to a considerable increase in the survival rate of mice and to a longer period (up to 20 days) of obtaining inoculative material from the spleen. The isolated cultures are characterized by a sharply slower growth on artificial culture media (up to 5-7 days as compared with 24-48 hours for the initial culture). The newly developed models have made it possible to control different stages of the infectious process in the induced increase or decrease of the virulent properties of the infective agent and in changes in the immune status of the host. As the result of these studies, in some mice (10%) infected with B. cepacia after the injection of gamma-hydroxybutyric acid lactone the infection has taken the acute form, while in the mice infected with P. aeruginosa no such effect has been observed. On the contrary, in the mice infected with P. aeruginosa and then receiving cyclophosphamide the transition of the infection into the acute form has been observed in 30% of the animals. In the mice infected with B. cepacia no such effect has been noted after the injection of this preparation. Different effects produced by cyclophosphamide and lactone are discussed from the positions of "quorum sensing" in pathogenic bacteria.

Animals↗
PubMedDate not supplied

[Genomics and gene engineering: rationale to the development of new means of tuberculosis control].

The review contains information on modern approaches to the development of antituberculosis vaccines and remedies. Data on the comparative effectiveness of different subunit and DNA vaccines against tuberculosis are presented. The use of comparative and structural genomics for the search and characterization of new Mycobacterium tuberculosis genes, whose products may prove to be important antigens for the development of vaccines or target proteins for remedies against tuberculosis, is considered.

Adjuvants, Immunologic↗
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[Role of apoptosis in the regulation of the infectious process].

Review on the influence of pathogenic bacteria on the apoptosis program of host cells. Many pathogenic bacteria posess mechanisms to control cell death, which makes it possible to maintain the optimum conditions for the development of infection. The mechanisms of the induction and suppression of apoptosis, worked out by bacteria, are very variable and realized as the result of complex interaction of biologically active bacterial molecules with concrete targets of signal paths leading to apoptosis. In case of intracellular parasitism the antiapoptosis activity of bacteria may be regarded as one of the mechanisms of the persistence of infective agents, ensuring the development of chronic infections.

Animals↗
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[Study on the polymorphism of the coagulase gene by the method of sequencing in methicillin-resistant Staphylococcus aureus strains, isolated in hospitals in different regions of Russia and Belarus].

This method was used for typing of 31 Staphylococcus aureus methicillin-resistant (MRSA) strains; of these, 27 were clinical isolates obtained in hospitals of different cities of Russia and Belarus and 4 were international epidemic strains EMRSA-1, -2, -3, -12. The sequencing of the variable area, located in the middle part of the coagulase gene between nucleotides 979-1355 and detected with the use of information technologies, was carried out. The results of this sequencing were compared with those of the earlier study on the polymorphism of the area of the same gene between nucleotides 1513-2188, carried out by the method of PCR-restrictive fragment length polymorphism. The sequencing of the part of the coagulase gene made it possible to confirm the presence of essential differences in the nucleotide sequences of the coagulase gene in international strains EMRSA-1, -3, -12, grounds for classifying clinical isolates of MRSA strains with two groups (4 and 5), as well as the genetic relationship of different phage types, isolated in different clinics. The study revealed considerable similarity in the nucleotide composition of strains EMRSA-2 and EMRSA-12 despite the fact that, according to the results of Cfol restriction of the 3'-end, they were classified with different groups; the study also revealed the identity of the nucleotide sequences of the coagulase gene in the cultures of group 5, isolated in hospitals of Moscow, St. Petersburg, Orenburg, and strain EMRSA-2, as well as methicillin-sensitive S. aureus strain 8325-4; in addition, in clinical isolates of group 4 and strain EMRSA-1 a considerable degree of homology was revealed. The study of two different loci made it possible to find out the strain with the recombinant form of the coagulase gene. The approach used in this study permitted the differentiation of the international epidemic strains EMRSA-1, -2, -3 and -12 into individual groups, which coincided with the results of Enright et al. (2002) who used multilocus sequencing.

Coagulase↗
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[The influence of bacteria of the Burkholderia cepacia and Pseudomonas aeruginosa complex on cell-mediated immune reactions in experimental animals].

The evidence has been obtained that various species, as well as individual strains having pathogenicity factors, produced different effect on the functional activity of immunocompetent B and T lymphocytes of mice infected intraperitoneally. The injection of live P. aerruginosa PA 103 and B. cepacia 8240 cells resulted in imunosuppression of antibody-forming cells, synthesizing antibodies to heterologous antigens. On the contrary, in the animals infected with B. cepacia 8236 the functional activity of B lymphocytes increased. An increase in the proliferative activity of spleen cells was noted in the presence of T and B mitogens after the infection of mice with P. aeruginosa PA 103 in comparison with B. cepacia 8236 and B. cepacia 8240 which produced a faintly pronounced modulating effect. The pathogenesis mechanisms of infections induced by these microorganisms as well as the development of chronic, persisting forms of the infectious process are discussed.

Animals↗