[In memory of Yuri Sergeevich Balashov (25.XII.1931-28.IX.2012)].

Biographical notes describe the life and scientific activities of Yuri Balashov, an outstanding Russian parasitologist, the Chief Editor of Parazitologiya.

[The directions and experiences of integration of clinical laboratory diagnostic and branch medicine].

The article considers the actual issues of teaching laboratory medicine to students of medical faculty and to physicians getting trained in different programs of postgraduate education. The major models of interaction between clinical physicians and specialists of laboratory diagnostic are considered. The proposed model of teaching of laboratory medicine is developed in collaboration with clinical chairs and is based on the principle of "clinical laboratory council of physicians". The analysis of clinical cases of specific patients and clinical analytical critiques are in the basement of the given system. The algorithm of considering one of situation tasks used in teaching is presented as example.

[Characteristic features of biodiversity in European ixodid ticks (Acari, Ixodidae) as vectors of diseses with natural foci].

The diapason of some biodiversity characteristics of ixodid ticks of the fauna of Europe and adjacent territories is analyzed. These characteristics include taxonomic and morphological diversity, the diversity of life cycles, host-parasite relations, species ranges, and biotopic associations. The significance of different aspects of biodiversity of ixodid ticks as a prerequisite of interrelations with pathogens with natural foci is estimated.

[Collection of ixodoid ticks in the Zoological Institute of Russian Academy of Sciences: its unique features and significance for decoding fundumental aspects of taxonomy and those connected with natural reservoirs].

Unique features of the collection of ixodoid ticks in the Zoological Institute of Russian Academy of Sciences (St. Petersburg, Russia) are characterized. The collection is stand out against a background of other world's collections by the presence of complete geographic series from whole ranges of species, including all active stages of ontogenesis. The results of basic and applied investigations obtained owing to the characteristics of this collection are summarized briefly. The contribution to the taxonomic investigations of ixodoid ticks connected with the problem of natural foci, based on the collection, is analyzed. Urgent directions of ongoing and future studies based on the collection are considered.

[Characteristic features of the ranks genus and subgenus, and an intercalary rank "species complex" in ixodid ticks (Acari: Ixodidae)].

The work was carries our from the standpoint of the morphological conception of species. Vast collections of the Zoological Institute of the Russian Academy of Science testify to the existence of hiatuses in both genera and subgenera of Palearctic ixodids at all active phases of their ontogenesis. The fact that the subgenera of Palearctic genera have been well studies is notes, and composition of the subgenera is presented. The question of a taxonomic intercalary rank "species complex" is considered in detail in the context of the coevolution between some complexes of closely related species of ixodid ticks and some closely related species (genospecies, strains) of pathogens. The question of the taxonomic rank "species complex" in ixodid ticks as a phyletic species association is postulated on the basis of comparative ontogenetic data. Nomenclature status of the intercalary association "species complex" is specified in conformity with the fourth edition of the International Code of Zoological Nomenclature. Species composition of most studied complexes is presented. Some variants of morphological differentiation between species complexes within subgenus are considered. Significance of the taxonomic concept "species complex" for zoological. parasitological, and medical aspects of the ixodid ticks study was evaluated. Prognostic significance of the rank "species complex" for the study of the relationships between ixodid ticks and pathogens is discussed.

[Intraspecific taxonomic differentiation in ticks (Acari: Ixodidae) in the view of the morphological conception of species].

The criterions for two most used intraspecific taxonomic ranks of ticks--subspecies and morphotype, have been formulated on the basis of the study of morphological variation in the distribution range of all active ontogenetic stages of 11 polymorphic species. All these species are vectors of transmissible diseases. They have vast distribution ranges and different types of host-parasite relationships. Subspecies have the complexes of visual morphological differences expressed in one or both sexes of mature ticks more limited, than those of related species. At immature stages differences of subspecies consist more often in morphometric characters and can be established by the methods of mathematical statistics only. Morphotypes, as a rule, differ at each corresponding stage by "their own" complexes of morphometric characters. All differential parameters of studied morphotypes are overlapped, but have statistically significant differences (by the Student's test). The concrete variations of differentiation by subspecies and morphotypes have been considered. The historical factors of intraspecific differentiation have been reconstructed for each species.

[Larval identification of species and subspecies of the genus Hyalomma (Acari: Ixodidae) from Russia and neighbouring territories].

The following species and subspecies of Hyalomma Koch, 1844 are recorded from Russia and neighbouring territories, including those involved in natural foci of tick-borne diseases: H. (Hyalomma) aegyptium (Linnaeus, 1758), H. (Euhyalomma) dromedarii Koch, 1844, H. (Euh.) asiaticum asiaticum Schulze et Schlottke, 1930, H. (Euh.) asiaticum caucasicum Pomerantzev, 1940, H. (Euh.) asiaticum kozlovi Olenev, 1931, H. (Euh.) anatolicum Koch, 1844, H. (Euh.) excavatum Koch, 1844, H. scupense Schulze, 1918, H. (Euh.) marginatum marginatum Koch, 1844, H. (Euh.) marginatum turanicum Pomerantzev, 1946, and H. (Euh.) marginatum rufipes Koch, 1844. The geographic distribution and host-parasite relationships of each taxon are discussed. Species characters of the larval stage, that can be distinguished using light microscopy, are found to be very few. These characters include shape of scutum, shape and rate of hypostome denticulation, shape and rate of the development of spurs on coxae I to III. Measurements of some morphological structure and their rations show statistically significant differences between some closely related species, even if qualitative discriminating characters are unknown. Only measurements and their ratios can be used for the discrimination of larval H. anatolicum from larval H. excavatum, because qualitative discriminating features have not been found for these species. The complex structure of the subspecific morhological differentiation of all parasitic stages in the polymorphic species H. asiaticum and H. marginatum is revealed. This structure probably reflects some peculiarities of the microevolutionary processes. Identification key for the larval stage of seven Hyalomma species is provided.

[Assessment of the preimaginal stages of the ticks collected from small mammals in Western and Northern Caucasus (Acari: Ixodidae)].

The exact identification of the preimaginal stages of the ticks collected from small mammals in Western and Northern Caucasus as a result of ten-year route investigations allowed us to obtain new data on the geographic ranges, altitude and biotopic preferences, and host-parasite relations of 11 species. A wide range of the joint occurrence (in the same locality, on the same host species, on the same host individual) is recorded for the first time for 10 species. The cohabitation of the each of 10 species with other 2-9 species has been found. The number of the cases of joint occurrence of different ixodid species on the same host individual is proportionate to the collection period in one locality. The cohabitation did not observed only for the species Ixodes ghilarovi, a high mountain ixodid species, which is for the first time recorded in 7 localities of Northern and Western Caucasus.

[Diagnosis of pigment-free optic tract tumors: clinical and morphoimmunohistochemical aspects].

The authors present the results of comparison of clinical, instrumental and histological, immunohistochemical and electron microscopic data on two pigment-free ciliochoroidal tumors. Differential diagnosis was made at each of the above stages of diagnosis. There is evidence that despite the similarity of the clinical syndrome, the spindle-cell type of the histological structure of both tumors, the latter were of various histogenesis. This was confirmed by the results of immunohistochemical and electron microscopic studies. Retrospective analysis of the data of immunohistochemical and echographic studies revealed the distinctive signs that could differentiate these two types of tumors at the stage of clinical and instrumental diagnosis.

[Morphological characteristics of stromal gastrointestinal tumors].

Stromal tumors are singled out from smooth muscle and neurogenic neoplasms into a special group due to differences in CD117 expression caused by mutation of c-kit gene. Out of 57 stromal tumors, 37 (64,9%) located in the stomach, 17 (29,8%) in the small intestine and 3 (5,3%) in the colon. Immunohistochemically, all the tumors expressed CD117 and vimentine. Smooth muscle actin was found in 82% tumors, S-100 protein in 75%, neuron-specific enolase in 66% cases. Malignant tumors were in 93% cases, and in 7% benign. Metastases were observed in 47.7% cases, recurrences in 14%. The liver was most frequent site of metastases (88.9%), peritoneum (51.9%). 21% patients died of progression of the underlying disease during the follow-up of 6-60 months.

[Morphological inversions during the ontogenesis of the ixodid ticks (Acari: Ixodidae) from the viewpoint of the hypermorphosis conception and their significance for systematics].

Morphological inversions during the ontogenesis of the ixodid ticks consist in the deranges of species-specific tendencies in the development of some external structures by the female line. The inversions, which included a wide range of organs and their fine structures, have been described for the first time in 14 species of 4 from 7 Palearctic ixodid genera. Emphasis is placed on the study of the structures, which serve as differential characters for closely related species. It is shown, that the using of the structures subjected to inversions is unavoidable in systematics because of the great similarity of closely related species, especially in immature stages. It is established by the data on the variability of all active stages in the species distribution ranges, that the degree of the inversions manifestation may somewhat fluctuate in different subspecies or geographic morphotypes of the same species, but the peculiarity of the inversions always remains a species-specific character. The cause of inversions origin is the evolution of the Ixodidae by the way of morpho-ecological specialization, namely hypertrophic, giantism, the growth of teguments in the period of nutrition act by pasture ambushing, which led to the derange of the development coordination of the organs during ontogenesis. Biological implication of the inversions is a guarantee of the adaptive potential of species during the process of microevolution. Even though the inversions make identification of closely related species difficult, their substantial importance is that they form integral species-specific character for the whole active part of the species ontogenesis.

[Some aspects of intraspecific variability of the closely related species of the Dermacentor marginatus complex (Acari: Ixodidae) as demonstration of microevolutionary process].

Individual and geographical variability of male conscutum pattern in five closely related species of the Dermacentor marginatus complex (D. marginatus, D. ushakovae, D. niveus, D. silvarum, D. nuttalli) has been examined. The pattern has been examined in three to six geographical samples within each specific distribution range. It was established that the pattern of the conscutum central area is subjected to individual and geographical variability on an extreme degree and gives very few intraspecific differential characters, but it shows interspecific differences in some cases. However the dark patches of marginal flank (npkappadelta and 3deltakappa respectively, see Fig. 3) show statistically significant differences in length in all geographical samples of the first four species. Characteristic features of ixodid ticks morpogenesis rule out to a considerable extent the possibility to trace geographical variability of the same characters by all stages of ontogenesis. In these cases, when it is possible, the tendencies to variability on different stages do not always coincide. There is no coordination within the species in the degree of differences of examined geographical samples by pattern and morphological characters, i. e. very complex polymorphis is observed. In the context of the evolution that kind of polymorphism of the geographical samples has provided the species with high adaptive potential for conquest of the extensive range and maintaining large numbers. The question of allopatric speciation of the closely related D. marginatus-D. silvarum with small secondary area of transgression their ranges, and sympatric speciation of the D. ushakovae-D. niveus is postulated.

Interaction with serum albumin as a factor of the photodynamic efficacy of novel bacteriopurpurinimide derivatives.

Optimization of the chemical structure of antitumor photosensitizers (PSs) is aimed at increasing their affinity to a transport protein, albumin and irreversible light-induced tumor cell damage. Bacteriopurpurinimide derivatives are promising PSs thanks to their ability to absorb light in the near infrared spectral region. Using spectrophotometry, we show that two new bacteriopurpurinimide derivatives with different substituents at the N atoms of the imide exocycle and the pyrrole ring A are capable of forming non-covalent complexes with human serum albumin (HSA). The association constant (calculated with the Benesi-Hildebrand equation) for N-ethoxybacteriopurpurinimide ethyloxime (compound 1) is higher than that for the methyl ether of methoxybacteriopurpurinimide (compound 2) (1.18×10(5) M-1 vs. 1.26×10(4) M(-1), respectively). Molecular modeling provides details of the atomic interactions between 1 and 2 and amino acid residues in the FA1 binding site of HSA. The ethoxy group stabilizes the position of 1 within this site due to hydrophobic interaction with the protein. The higher affinity of 1 for HSA makes this compound more potent than 2 in photodynamic therapy for cultured human colon carcinoma cells. Photoactivation of 1 and 2 in cells induces rapid (within a few minutes of irradiation) necrosis. This mechanism of cell death may be efficient for eliminating tumors resistant to other therapies.

Relationships between species of the Rhipicephalus sanguineus group: a molecular approach.

The biosystematic status of species belonging to the Rhipicephalus sanguineus group is difficult to determine by phenotypic methods and has been subject to frequent revisions and ongoing debate. Yet, the differentiation of species within this complex is of clinical importance especially in veterinary medicine due to different host specificities of the transmitted pathogens. In order to generate quantifiable and comparable data independent of environmental influences, a section of the second internal transcribed spacer (ITS2) of the rRNA gene was sequenced for 6 species belonging to the Rhipicephalus sanguineus complex: Rhipicephalus sanguineus sensu stricto, R. turanicus, R. rossicus, R. pumilio, R. pusillus, and R. camicasi. Rhipicephalus sanguineus s. str. and R. turanicus as well as R. pumilio and R. rossicus were found to have a close genetic relationship compatible with possible conspecificities. Conversely, R. pusillus was found to have the most distant relationship to the other species.

Alterations of melanin synthesis in human melanoma cells selected in vitro for multidrug resistance.

Previous data showing the correlation of multidrug resistance (MDR) and differentiation in tumor cell populations (Melloni et al. 1988; Stavrovskaya et al. 1990) suggest that: 1) isolation of MDR cells by cytostatic drugs leads to the selection of more differentiated cell variants and 2) in more differentiated cell variants the activity of MDR-related P-glycoprotein (Pgp) is more prominent than in less differentiated cells. Here we used human melanoma cell line mS and two variants selected from mS population: a) MDR variant of mS selected by colchicine (mS-0.5) and b) mS-trRAR/2--variant obtained by introduction of expressing retinoic acid receptor RAR-alpha cDNA into mS cell. The differentiation status, expression of MDR1 gene and Pgp functioning were compared in wild-type cells and mS variants. Electron microscopic examination of melanosomes showed that the mS-0.5 subline comprised more differentiating cells in the population than parental mS cultures and that these cells were at later stages of melanogenesis. The increase in the degree of differentiation in mS-0.5 population coincided with MDR1 gene overexpression, occurrence of Pgp molecules on the cell membrane and acceleration of Pgp-mediated Rhodamine 123 (Rh123) efflux. mS-trRAR/2, proved to be more differentiated than mS cells. The MDR1 mRNA level and Rh123 efflux were not elevated in mS-trRAR/2 cells, however, retinoic acid (RA) treatment increased both the degree of differentiation and Rh123 efflux in mS-trRAR/2 to a greater extent than in mS cultures. Thus, the data obtained in this study are in favor of the suppositions mentioned above. The mechanisms of coordinated alterations of differentiation and Pgp activity in MDR cells are discussed.

[Characteristics of the effects of artificial alkalosis on electrical activity of the brain and ultrastructure of blood cells in oncologic patients]. / Osobennosti vliianiia iskusstvennogo alkaloza na élektricheskuiu aktivnost' mozga i ul'trastrukturu kletok krovi u onkologicheskikh bol'nykh.

The authors examined 40 patients with malignant tumors of various histogenesis, sites and extent, as well as 5 patients with benign tumors and other non-tumorous diseases. They also studied their electroencephalography and peripheral blood lymphocytic and erythrocytic ultrastructure in metabolic alkalosis temporarily induced by intravenous sodium hydrogen carbonate. In cancer patients without late metastases, alkalosis caused a transient normalization of previously altered electroencephalography, erythrocyte disaggregation and substantially reduced the count of killer cells in small and middle lymphocytes. These findings suggest that patients with malignant neoplasms have a generalized intracellular acidosis which can be temporarily abolished by plasma alkalinization.

[Electron microscopy in the diagnosis of soft tissue angiogenic tumors]. / Elektronnaia mikroskopiia v diagnostike angiogennykh opukholei miagkikh tkanei.

Thirteen angiogenic tumours of soft tissues (benign and malignant variants of these neoplasms) were studied electron microscopically. The data obtained indicate that an electron microscopic examination allows performing differential diagnosis within the group of angiogenic tumours and distinguishing them from the neoplasms of other histogenesis.

[Ultrastructural features of benign and malignant lesions of a melanocytic nature]. / Ul'trastrukturnye osobennosti dobrokachestvennykh i zlokachestvennykh porazhenii melanotsitarnoi prirody.

23 melanomas having the thickness, according to Breslow, up to 1.5 mm and 12 benign melanocytic tumours are studied. Ultrastructural examination gives additional information for differentiating benign and malignant melanocytic tumours. It is necessary to take into consideration such signs as the number and qualitative properties of melanosomes and premelanosomes, structure of nuclear membrane, that of nucleoli, non-specific microfilaments and mast cell infiltration of the tumour stroma. Some ultrastructural difference between lentigo-melanoma and other histological tumour types are noted.

[Hemangiopericytoma of the bone]. / Gemangioperitsitoma kosti.

A case of tibia hemangiopericytoma in a male of 19 is described. The diagnosis is confirmed electron-microscopically.

[Ultrastructure of a granular-cell breast tumor]. / Ul'trastruktura zernistokletochnoi opukholi molochnoi zhelezy.

Electron microscopic examination of a rare granular cell tumour of the mammary gland that provoked difficulties in the diagnosis was performed. Ultrastructural organization of the tumour allowed one to establish a proper diagnosis and to confirm the hypothesis on the origin of this tumour from Schwann's cells.