CYP2C19*2 gene variant (G681A, rs4244285) as a prognostic marker for the clinical course of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is the most common type of paraproteinemic hemoblastosis, which is characterized by an aggressive course, high mortality and a large number of complications. The G681A variant (*2, rs4244285) of the CYP2C19 gene leads to the formation of an inactive enzyme and, as a consequence, may affect the development and course of MM. The aim of this research was to analyze the effect of the G681A variant of the CYP2C19 gene on the risk of the development of MM and its course. MATERIALS AND METHODS: The study enrolled 158 patients with MM, who underwent standard clinical and laboratory studies: cytological, general clinical, biochemical, as well as molecular cytogenetic and molecular genetic. Cytogenetic analysis of chromosome abnormalities was performed using interphase fluorescence in situ hybridization. Genotyping by the G681A variant of the CYP2C19 gene was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No association was found between the G681A variant of the CYP2C19 gene and the risk of developing MM. The association between the presence of the G allele and GG genotypes with significant changes in clinical and biochemical parameters (plasma cell count, α2-globulin, calcium content) in MM patients has been established. In the presence of the G allele of the CYP2C19 gene, the development of chromosomal rearrangements del(13q14.2) or del(13q34) with significantly increased levels of albumin occurs more frequently. CONCLUSIONS: The G681A variant of the CYP2C19 gene does not affect the risk of developing MM, but it is associated with significant changes in the clinical and biochemical parameters that determine the severity of the disease and its prognosis. Further research is important to develop new target strategies and maintenance therapy for carriers of different variants of the CYP2C19 gene (G681A).

DEVELOPMENT OF GANGLIONOPATHY AND TABETIC VISCERAL CRISES ON THE BACKGROUND OF POLYRADICULONEUROPATHY ASSOCIATED WITH MONOCLONAL GAMMOPATHY (CASE REPORT).

The article presents an analysis of the clinical occurrence of development of chronic polyradiculoneuropathy associated with monoclonal IgG/k (kappa) gammopathy of the undetermined significance. The peculiarity of this occurrence is the uniqueness of the development of the symptoms which are characteristic of tabes dorsalis in this pathology with episodic severe visceral crises and also with ganglionopathy. The example describes the clinical polymorphism of the course of visceral crises, the problems of their diagnosis and as a consequence of inadequate treatment with the development of severe social maladaptation. The importance of timely diagnosis and treatment of such conditions is discussed.

[Pneumococcus pathogenicity factors and their protective properties].

Owing to rapid development of molecular-biological and genetic methods of research in infectology as well as use of adequate models (tissue colonization of human respiratory epithelium, mice models of colonization, sepsis and meningitis), a significant progress in the field of pneumococcus pathogenicity factors has been made in the last decades. Aside from the well-known pathogenicity factor--capsule polysaccharide, to date several dozens of surface proteins providing adhesion, colonization and invasion have been detected in pneumococcus. Pneumolysin is a toxic factor and at the same time brain invasion factor. Many of the known pathogenicity factors play a role in formation of biofilm that facilitates prolonged colonization of nasopharynx. Protective activity has been proved for some of the surface proteins and pneumolysin that forms the base for development of novel rational pneumococcal vaccines as an alternative to polysaccharide.

[Experience of using thalidomide in the treatment of patients with multiple myeloma].

The results of treatment of patients with multiple myeloma with thalidomide and complications of this treatment are presented. Monotherapy with thalidomide and its combinations with corticosteroids and cytostatics is an effective as first line treatment and as a treatment of patients with refractory disease. The most common side effect is toxic neuropathy. Other complications are less common and are easily controlled with medications.

[Bacterial carriage as a form of persistence of meningococci].

Features of meningococcal carriage as a form of microorganism's persistence necessary for survival and species preservation are discussed in this review. New data on genetic heterogeneity of meningococcal population, which is major determinant of occurrence-of asymptomatic forms, are presented. Process of formation of meningococcal biofilms is described. Materials about systemic and local immunity developed during meningococcal carriage and possible influence of vaccination on carriage rate are reviewed. Role of persistence of meningococci in stimulation of immune protection of population from severe forms is discussed.

[Epidemic process of gonorrhea in modern world].

Gonorrhea in spite of its fully elucidated etiopathogenesis and available drugs for etiotropic therapy belongs to infections which are not controlled by vaccination due to absence of immunity formation. Analysis of scientific publication, statistical materials and WHO's data showed that epidemic process of gonorrhea infection depends mainly from people's behaviour, first of all, sexual. Modern epidemic process of gonorrhea infection consists from irregular increases and decreases of incidence due to various reasons. Reasons for increases of incidence appear to be simultaneous action of a range of biologic and anthropogenic factors. First reason--rapid increase of resistance of gonococci to widely used antibacterial preparations as well as synergy of pathogenic effects between HIV and gonococci; anthropogenic--wars, increase of high-risk groups due to urbanization, use of oral contraceptives, rise of prostitution, migration, inadequate access to medical care, poverty, intensification of intercourses (including hetero- and homosexual) between people, as well as demographic changes--increase of proportion of young people in population structure. Same but reciprocal factors lead to decrease of morbidity. Of them, the following were considered as most important: mass implementation of new effective antimicrobial drug as well as intensification of sanitary education, availability of early diagnostics and treatment, increase of material and cultural standards of life, decrease in number of persons belonging to high risk groups. Yet, capabilities of modern science expressed only in continuous development of new antibacterial drugs active against circulating population of gonococci, which is resistant to previously used drug.

[Molecular biological basis of the gonococcal pathogenicity and specific features of immune response].

The pathogenicity factors of gonococci--pili, outer membrane proteins (porins, Opa proteins, iron-regulated proteins), lipooligosaccharide, a number of secreted enzymes--are considered according to our knowledge of their relationships with different human specialized cells, including neutrophils. The main stages of the infectious process of gonorrhea are described in the light of modern concept of "parasite-host" relationships. Materials on the instability of gonococcal antigens, and frequent formation of new antigenic variants are presented. This is the main cause of the absence of postinfectious immunity in gonorrhea and the limitation of possibility for creating effective vaccine in the near future.

[Reactions and complications caused by thrombocyte concentrate transfusions]. / Reaktsiï ta uskladennia, zumovleni zastosuvanniam kontsentratu trombotsytiv.

The review contains current data on complications developing in the wake of employing thrombocytes concentrate in clinical settings. Complication patterns are submitted, causes thereof are analyzed. Technical aspects are discussed of optimum measures to be implemented in transfusions of the thrombocytes concentrate.

[Genetic structure of Corynebacterium diphtheriae strains isolated in Russia during epidemics of various intensity]. / Geneticheskaia struktura shtammov Corynebacterium diphtheriae, vydelennykh v Rossii pri raznoi intensivnosti épidemicheskogo protsessa difterii.

The genetic structure of C. dipthteriae toxigenic strains isolated in Russia during the period of more than 50 years was analysed. The use of the method of ribotyping made it possible to register 17 C. diphtheriae ribotypes. The study revealed that the genetic structure of C. diphtheriae population varied in the dynamics of the epidemic process: each epidemic cycle characterized by predominant spread of epidemic strains of definite biovars and ribotypes. Thus, C. diphtheriae strains of biovar gravis, ribotype M11, dominated in the 40-60 years and C. diphtheriae strains of biovar mitis, closely related ribotypes M1 and M1v, dominated in the 80 years. During the last epidemic rise of diphtheriae morbidity in the 90 s C. diphtheriae strains of biovar gravis, closely related ribotypes G1 and G4, dominated among circulating strains. The proportion of these ribotypes began to increase 3 years before the rise of morbidity. The data of microbiological monitoring are recommended for use in the prognostication of the development of the epidemic process of diphtheria infection.

[Molecular and biological mechanisms of the meningococcal carrier state]. / Molekuliarno-biologicheskie mekhanizmy meningokokkovogo bakterionositel'stva.

A review of the results of the latest molecular biological investigations on the problem of the formation of meningococcal carrier state, the colonization of human nasopharynx. The process of the adhesion of meningococci to epithelial cells by means of fimbrial and nonfimbrial adhesins, the transmission of signals between bacterial and epithelial cells, as well as the role phasic changes in the structure of meningococci in the process of adhesion are considered. The data on the penetration of meningococci into the epithelium and their fate within the cell are discussed. The biomolecular mechanisms of iron uptake by meningococci at the stage of their colonization of the nasopharyngoal mucosa are considered. The aspects of the prophylaxis of meningococcal carrier state are analyzed.

[The pathogenicity factors of Streptococcus pneumoniae strains causing meningitis]. / Faktory patogennosti shtammov Streptococcus pneumoniae, vyzvavshikh meningit.

Pneumococcal meningitis was registered in St. Petersburg in 1985-1991, morbidity rate being 1.7-2.3 cases per 100,000 children, including 7.4-19.8 cases among children under 1 year. Two thirds of the pneumococcal strains isolated in cases of meningitis belonged to serovars 19, 1, 6, 15 and 2. The comparative study of pneumococcal strains revealed that the presence of capsules, pneumolysin, high hyaluronidase activity or belonging to serovars 1 and 2 (irrespective of their hyaluronidase titers) were the most important factors contributing to the development of generalized infection. The role of such a factor as virulence for mice is not yet clear.

[Streptococcus pneumoniae adhesion]. / Adgeziia Streptococcus pneumoniae.

The adhesive capacity of 425 S.pneumoniae strains (S- and R-forms) isolated from children with various clinical forms of pneumococcal infection was studied with the use of the epithelium of oral cavity as a model. The strains isolated from patients with meningitis and otitis appeared to be less adhesive than the strains isolated from mucous membrane of respiratory tracts. In all clinical forms of infections the adhesive capacity of S.pneumoniae S-forms was significantly lower than that of R-forms. The hyaluronidase activity and the adhesive capacity of S.pneumoniae strains were found to be inversely related.

[The role of hyaluronidase in the occurrence of a generalized pneumococcal infection]. / Rol' gialuronidazy v vozniknovenii generalizovannoi pnevmokokkovoi infektsii.

The hyaluronidase activity of pneumococcal strains isolated from 39 patients with purulent meningitis, 26 patients with acute internal otitis and 130 healthy carriers was studied. All strains isolated from patients with purulent meningitis and meningoencephalitis and 84.6% of strains isolated in cases of otitis were found to have hyaluronidase, while in healthy children hyaluronidase-synthesizing strains were detected only in 11.5% of cases. Hyaluronidase titers in pneumococcal strains isolated from patients with meningitis and meningoencephalitis were significantly higher than in strains causing purulent otitis. At the same time strains with high hyaluronidase titers were also isolated from 7% of healthy carriers. Noncapsular pneumococcal strains had no hyaluronidase. The average value of the reverse correlation between hyaluronidase activity and the virulence of strains for mice was established. Hyaluronidase activity did not correlate with different serotypes of pneumococcal strains. The intranasal administration of hyaluronidase in high titers (> or = 1:8) to mice and rats led to the penetration of the infective agent through the hematoencephalic barrier of the animals and to their death from generalized pneumococcal infection. The role of hyaluronidase as the invasiveness factor of pneumococci was confirmed in experiments on the intranasal infection of mice with low active strains mixed with the preparation of exogenous hyaluronidase.

[The Neisseria meningitidis serotypes and subtypes circulating among bacterial carriers in Moscow (1989-1991)]. / Serotipy i subtipy Neisseria meningitidis, tsirkuliruiushchikh sredi bakterionositelei v Moskve (1989--1991 gg.).

N. meningitidis strains isolated from 218 healthy carriers in 1989-1991 in closed communities of adults, irrespective of cases of meningococcal infection registered in these communities, were characterized with a variety of different type and subtype antigens. Only in 139 strains (63.76%) their types and/or subtypes could be determined with the use of a set of 6 serotypes and 11 subtypes of monoclonal antibodies. 26 group B strains and 31 group C strains had multiple antigenic composition. 13 group A strains were found to be more homogeneous: 8 of them, isolated in one area, belonged, according to Dr. Achtman's data, to a definite clone VI-1, heretofore unknown. No prevailing serotype/subtype could be revealed, which reflected the wide heterogeneity of N. meningitidis at the period of the decrease of morbidity in meningococcal infection. The observed stability of serotype/subtype of strains, isolated from the same carriers and circulating in the same communities, suggests that the serotype/subtype of N. meningitidis is a valuable epidemiological marker.