[Personality self-actualization: an independent additional risk factor of myocardial infarction and unstable angina].

It is shown for the first time that changes of self-actualization (SA) in patients with CHD are the main risk factor of myocardial infarction (MI) and unstable angina (UA). The clinical course and prognosis of MI correlate with SA prior to the development of an acute coronary event. Isolated correlations exist between CHD risk factors and results of SA questionnaire studies. SA personality peculiarities in patients with MI and UA account for more than 50% dispersion of the results of linear factor analysis.

[Malaria in Moscow (2006-2007): monitoring of the situation and assessment of antimalaria measures].

The malaria situation in Moscow in 2007 versus 2006 improved--the cases of malaria reduced by 16.3%. A total of 30 new cases of malaria were notified (46 cases in 2006), of them there were 34 imported cases and 4 secondary cases to imported ones. In 2007, the proportion of tertian malaria cases reduced to 55.3% versus 60.9% in 2006. As compared with 2005, in 2007 the cases of locally transmitted malaria decreased by 5 times--from 20 to 4, only 1 case of infection occurred in Moscow (Central Administrative District) and 3 cases took place in the Moscow Region (Ramensky, Stupinsky, and Dmitrovsky districts). Cases of malaria were notified in all administrative districts, with their largest number in the South-Western Administrative District of Moscow due to the detection of ill students from the Russian University of People's Friendship who had come to study from African countries. In accordance to the performed certification of water reservoirs in 2007, a total of 722 Moscow water reservoirs of an area of 1569 ha were registered at the Administration of the Russian Agency for Consumer Surveillance. The examination frequency of all water reservoirs was about 13 per season, including 20 anopheles-containing ones. The larvae of bloodsucking mosquitoes inhabited 541 (75%) water reservoirs, including 461 (63%) water reservoirs occupied by the malaria vector. As compared with 2006, the area of treatments increased by 351 ha. In the summer, a total of 2133.3 ha ofwater reservoirs were treated, including 2009.5 ha against larvae of malaria mosquitoes. The bulk of water reservoirs were exposed to triple-quadruple treatments.

[Smoking affects metal-ecotoxicant accumulation and genotoxic reactions in leukocytes].

The investigation was concerned with the influence of smoking on manganese (Mn), lead (Pb) and cadmium (Cd) content in the blood of metropolitan groups of varying age as well as on genotoxic reactions in leukocytes after test irradiation ex vivo. The study involved 325 inhabitants of St.Petersburg, aged 10-90 years. Venous blood was assayed for metal ecotoxicant content using standard AAS-flame method and DNA leukocyte decay following test irradiation (2Gy) ex vivo. Aging was shown to involve a sequence of consistently rising metal levels: Cd - Mn Pb. Relative accumulation of Pb was greater in males while that of Mn - in females. The rates of Cd, Mn, Pb accumulation in smokers were higher than in non-smokers. Smoking promoted genotoxic response to testing exposure which induced Cd-related disturbances of DHA repair system in males. Among smoking females, risk of adverse effects rose as a result of concurrent action of the genotoxic factor. It was also evident among female non-smokers when radiation was used in conjunction with enhanced concentrations of Mn and Cd. Hence, correlations between smoking and Cd, Mn, Pb accumulation, on the one hand, and Cd-related accumulation and enhanced genotoxic response in leukocytes, on the other, were established. It is likely that carcinogenic risk of tobacco smoking should be accounted for by both mere presence of a carcinogenic agent and its potential to promote Cd level thus inhibiting withdrawal of carcinogenic DNA adducts from the cellular genome.

[Monomers for oligonucleotide synthesis with linkers carrying reactive residues: II. Synthesis of phosphoamidites based of uridine and cytosine and containing a linker with methoxyoxalamide groups in position 2']. / Monomery dlia oligonukleotidnogo sinteza s linkerami, nesushchimi reaktsionnosposobnye ostatki 2. Sintez fosfamiditov na osnove uridina i tsidina, soderzhashchikh v 2'-polozhenii linker s metoksioksalilamidnymi gruppami.

A convenient preparative synthesis of 2'-amino-2'-deoxyuridine was developed. Starting from 2'-amino-2'-deoxyuridine and 2'-amino-2'-deoxycytidine, monomers for the phosphoamidite oligonucleotide synthesis were obtained that carry a linker with methoxyoxalamide groups in position 2'. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 3; see also http://www.maik.ru.

[Monomers for oligonucleotide synthesis with linkers carrying reactive residues: I. Synthesis of deoxynucleoside derivatives with methoxyoxalamide groups in heterocyclic bases]. / Monomery dlia oligonukleotidnogo sinteza s linkerami, nesushchimi reaktsionnosposobnye ostatki 1. Sintez proizvodnnykh dezoksinukleotidov s metoksioksalilamidnymi gruppami, prisoedinennymi k geterotsiklicheskim osnovaniiam.

A number of monomers for the standard phosphoamidite oligodeoxynucleotide synthesis that carry reactive methoxyoxalamide groups attached to the thymidine, 2'-deoxycytidine, and 2'-deoxyadenosine heterocyclic bases were prepared. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 3; see also http://www.maik.ru.

[The influence of geomagnetic field on blood leukocyte radiosensitivity and gender determination in humans]. / Vliianie geomagnitnogo polia na radiochuvstvitel'nost' leikotsitov krovi i determinatsiiu pola cheloveka.

The gender and age features of the geomagnetic field (GMF) influence (K-indexes) on the leukocyte radiosensitivity (S) in human blood in case of normal and enhanced levels of metal-ecotoxicants (Pb, Cd, Hg, Mn, Zn, Cu) in blood was studied, as well as the impact of the GMF intensity alterations on the child gender determination. In the whole studied population (n = 244) it was observed a negative relationship between S- and K-indexes. It was shown that the most changes of blood leukocyte radiosensitivity depended on the GMF oscillations in men older than 45 years. In case of metal-ecotoxicant concentrations in blood near normal level there were observed significant relationships between S- and K-indexes, which was infringed by more than 2-fold excess of these toxicant concentrations in blood. Retrospective analysis showed that in case of the GMF intensity enhancement in the conception moment the girls were born mostly, and in case of the lowering--the boys were.

[Reagents for modification of protein-nucleic complexes. III. Site-specific photomodification of elongation complex of DNA polymerase beta with arylazide derivatives of primers sensitized with fluorescent ATP gamma-amide]. / Reagenty dlia modofikatsii belkovo-nukleinovykh kompleksov. III. Sait-spetsificheskaia fotomodifikatsiia élongiruiushchego kompleksa DNK-polimerazy beta arilazidnymi proizvodnymi praimerov, sensibilizirovannaia fluorestsentnymi gamma-amidami ATP.

ATP gamma-amides containing in gamma-N-position 1-methylpyrene, 9-methylanthracene, 10-chloro-9-methylanthracene, and 3-methylperylene residues were synthesized and characterized. These compounds were used as sensitizers of site-specific photomodification of the reconstituted elongating complex of the mammalian DNA polymerase beta. The photomodification was carried out with the use of photoaffine reagents, which were synthesized in situ by the 5'-(32)P-labeled primers extension with photoactive analogues of dCTP containing in the exo-N-position of cytosine various perfluoroarylazide groups. The effect of structures of the sensitizers and photoactive reagents on the efficiency and selectivity of photolinking of primers to the enzyme and template, as well as formation of a number of other photomodification products was studied. It was shown that the sensitizers containing 10-chloro-9-methylanthracene and 3-methylperylene residues allow preparation of photolinks in such irradiation conditions when photomodification in their absence is not essentially observed.

Photosensitized and catalytic oxidation of DNA by metallophthalocyanine-oligonucleotide conjugates.

The synthesis of new metallophthalocyanine-oligonucleotide conjugates is reported. These conjugates can cause sequence-specific photosensitized or catalytic oxidation of DNA by molecular oxygen.

[Effect of linker length on the photomodification process of tyrosine residues in N-(tyrosyl)-N'-(5-azido-2-nitrobenzoyl)diaminoalkanes]. / Vliianie dliny linkera na protsess fotomodifikatsii ostatka tirozina v N-(tirozil)-N'-(5-azido-2-nitrobenzoil)diaminoalkanakh.

N-(Tyrosyl)-N'-(5-azido-2-nitrobenzoyl)-1,4-diaminobutane, containing a Tyr residue connected with the photoreactive aryl azide group through the diaminobutylene linker, was synthesized as a model for studying the photomodification of Tyr residues in proteins. This compound and the compound with a shorter, 1,2-diaminoethylene linker, obtained previously, were subjected to computer modeling to find their minimal-energy conformations. The aromatic rings of Tyr and 5-azido-2-nitrobenzoic acid residues in the latter compound were localized in parallel planes at a distance of approximately 0.3 nm between them and were shown to be implicated in stacking interactions. On the contrary, the planes of aromatic rings of the former compound with a longer, diaminobutylene linker were found to be situated perpendicularly to each other, with the distance between the centers of the rings being approximately 0.6 nm. The computer analysis was confirmed by experimental results: when studying the photomodification of the compound with the diaminobutylene linker, neither stable products of the Tyr photomodification nor unstable products capable of transformation into stable products in the dark were found. On the contrary, such products were previously identified in the case of the compound with diaminoethylene linker. The formation of amino, nitro, azoxy, and azo derivatives was common for the photomodification of both compounds.

[Sensitized photomodification of DNA with binary sysytems of oligonucleotide conjugates. VI. Effect of substituents in the anthracene residue of the sensitizer]. / Sensibilizirovannaia fotomodifikatsiia DNK binarnymi sistemami oligonukleotidnykh kon''iugatov. VI. Vliianie zamestitelei v antratsenovom ostatke sensibilizatora.

Photomodification of ssDNA by binary systems of oligonucleotide conjugates complementary to the adjacent sequences of the target DNA was studied. One of the conjugates comprised a substituted anthracene as a sensitizer; the other, p-azidotetrafluorobenzaldehyde 3-aminopropionylhydrazone as a photoreagent. The sensitized photomodification is initiated by the 365-580-nm light through an efficient energy transfer from the photoexcitated sensitizer onto the photoreagent in a complementary complex of the binary system with the DNA target where the sensitizer and the photoreagent are sterically converged. Influence of substituents in the anthracene residue on the efficiency of the DNA sensitized photomodification was considered. The oligonucleotide conjugate of anthracene-9-al 3-aminopropionylhydrazone allows highly specific initiation of the sensitized photomodification upon irradiation with visible light at > 460 nm in conditions generating no photoreaction in the sensitizer's absence.

Synthesis of base-substituted dUTP analogues carrying a photoreactive group and their application to study human replication protein A.

Analogues of dUTP bearing a photoreactive 2-nitro-5-azidobenzoyl (NAB) group linked via spacers of varying length (n = 2, 4, 7-13 atoms) to the 5-position of the uridine ring (NAB-n-dUTP) were synthesized and characterized. DNA polymerase beta efficiently incorporated these analogues into synthetic primer-template substrates in place of TTP, which allowed us to selectively introduce a photoreactive group at the 3' primer terminus. After completing photoreactive primer synthesis, the reaction mixtures were irradiated with monochromatic UV light (315 nm) in the presence of human replication protein A (RPA), a heterotrimer consisting of three subunits with molecular mass 70 kDa (p70), 32 kDa (p32), and 14 kDa (p14), and were separated by SDS-PAGE. The photoreactive primers cross-linked directly with p70 and p32, but cross-linking of p14 was not achieved even by varying the length of the spacer group. The data speak in favor of the protection of p14 by other RPA subunits from the interaction with 3'-end of the primer. Cross-linking of substrates to pol beta is inhibited when the analogue bears a short spacer (n = 2, 4, 7, and 8), but this is abrogated somewhat when longer spacers (n = 9-13) are examined. On the basis of these observations, we suggest that RPA and pol beta form a complex on primer-template substrates.

[The synthesis of a cobalt(II) tetracarboxyphthalocyanine- deoxyribooligonucleotide conjugate as a reagent for the directed DNA modification]. / Sintez kon"iugata tetrakarboksiftalotsianina kobal'ta (II) s dezoksiribooligonukleotidom, reagenta dlia napravlennoi modofikatsii DNK.

The cobalt(II) tetracarboxyphthalocyanine-deoxyribonucleotide pd(TCTTCCCA) conjugate was synthesized. The phthalocyanine N-succinimide ester prepared from phthalocyanine using DCC was mixed in DMF with an aqueous solution of the oligonucleotide bearing a 1,3-diaminopropane linker at the 5'-phosphate. The resulting conjugate was tested in the intraduplex reaction with target 14-mer and 22-mer oligonucleotides containing conjugate-complementary sequences. In the presence of O2 and a thiol (2-mercaptoethanol or DTT) as a coupled reducer or H2O2, sequence-specific DNA modification was observed that caused the cleavage of the target upon treatment with piperidine.

[Sensitized photomodification of DNA with binary systems of oligonucleotide conjugates. V. Effect of the structure of the target DNA. Quantitative photomodification]. / Sensibilizirovannaia fotomodifikatsiia DNK binarnymi sistemami oligonukleotidnykh kon''iugatov. V. Vliianie stroeniia DNK-misheni. Kolichestvennaia fotomodifikatsiia.

A sensitized photomodification of several single-stranded target DNAs by binary systems of oligonucleotide conjugates complementary to the adjacent regions of DNA was performed. One of the conjugates contained a sensitizer (pyrene, anthracene, or 1,2-benzanthracene), and another conjugate contained a photoreagent 4-azidotetrafluorobenzalhydrazone. The sensitized photomodification is initiated by irradiation at 365-580 nm due to effective energy transfer from the excited sensitizer to the photoreagent in a complementary complex of the binary system with the target DNA where the sensitizer and photoreagent are brought sterically together. Conditions for the quantitative photomodification of a single-stranded DNA by the binary system of oligonucleotide conjugates were found. The maximum degree of photomodification depends on the number of guanosine residues in the (pG)n sequence of the target DNA at the modification site: at n = 1 the yield of covalent adducts was 62-68%, at n = 2, 75-82%, and at n = 4, 98-99%.

Synthesis of new photocross-linking 5-C-base-substituted UTP analogs and their application in highly selective affinity labelling of the tick-borne encephalitis virus RNA replicase proteins.

A new photocross-linking 5-C-base-substituted UTP analogs, carrying 4-azidoperfluorobenzoyl and 4-azidoaniline residues were synthesized. Two flavivirus proteins NS5 and NS3 are shown to be labelled after RNA synthesis in the presence of the analogs, irradiation (lambda > 300 nm) and subsequent [alpha-32P]NTP incorporation.

5-[3-(E)-(4-azido-2,3,5,6-tetrafluorobenzamido)propenyl-1]-2'-deoxy- uridine-5'-triphosphate substitutes for thymidine-5'-triphosphate in the polymerase chain reaction.

The DNA targets may be labeled and simultaneously amplified in the polymerase chain reaction (PCR) using a pair of respective primers after elongation with nucleoside-5'-triphosphates carrying photoreactive groups. The amplified DNA may be subsequently photoactivated by irradiation above 300 nm, resulting in photo-cross-linking of the strands. For this goal 5-[3-(E)-(4-azido-2,3,5,6-tetrafluorobenzamido)propenyl-1]-, 5-{N-[N'-(4-azido-2,3,5, 6-tetrafluorobenzoyl)-3-aminopropionyl]aminomethyl}-, and 5-{N-[N'-(2-nitro-5-azidobenzoyl)-3-aminopropionyl]aminomethyl}-2'-de oxyuridine-5'-triphosphate (VII, VIa, and VIb) derivatives have been synthesized. It was found that VII is capable of efficiently elongating DNA primers with both Klenow fragment DNA polymerase I and Thermus aquaticus DNA polymerase. Thereto, it turned out to provide quantitative incorporation in DNA as revealed by the formation of the full-length amplificate by PCR in the presence of this photoreactive analogue without any dilution with natural dTTP. On the contrary, it was found, that incorporation of VIa and VIb do not permit further DNA replication.

[The chronic fatigue syndrome]. / Sindrom khronicheskoi utomliaemosti.

CFIDS (chronic fatigue and immune disfunction syndrome) is also known as CFS (chronic fatigue syndrome), CEBV (chronic Epstein-Barr virus), M.E. (myalgic encephalomyelitis), yuppie flu and by other names. It is a complex illness characterized by incapacitating fatigue (experienced as exhaustion and extremely poor stamina), neurological problems and a constellation of symptoms that can resemble many disorders, including; mononucleosis, multiple sclerosis, fibromyalgia, AIDS-related complex (ARC) and autoimmune diseases such as lupus. These symptoms tend to wax and wane, but any often severely debilitating and may last for many months or years. All sections of the population (including children) are at risk, but women under 45 seem to be most susceptible. The investigators suggest that CFIDS results from dysfunction of the immune system. The exact nature of this dysfunction is not yet well defined, but it can generally be viewed as an unregulated or overactive state which is responsible for most of the symptoms. There is also evidence of some immune suppression in CFIDS. None of the treatments is consistently satisfactory, but some may be helpful: psychotherapy, physiotherapy, exercise programs, acupunctures, small doses of antidepressants, etc.

[Photoactive ethidium and azidoethidium dyes. Synthesis, properties, and covalent bonding to oligodeoxynucleotides]. / Fotoaktivnye étidievye i azidoétidievye krasiteli. Sintez, svoistvai kovalentnoe prisoedinenie k oligodezoksinukleotidam.

Methods of synthesis of ethidium and azidoethidium dyes, containing the primary aliphatic amino group of the 3-aminopropinoic acid residue were developed. The derivatives were characterized by spectral methods (NMR, UV- and fluorescent spectroscopy). Complex formation of ethidium dyes with DNA was studied by fluorescent technique. The stoichiometry of the dye--DNA complex was 1:4 (dye to base pair) for all the derivatives. Photoreactivity of azidoethidium dyes was 10(3) times higher and the quantum yield of the photoproducts was 10(5) times higher than those for ethidium dyes. A method of preparation of 5'-phosphoramide photoreactive oligodeoxynucleotide derivatives was suggested, with ethidium derivative of heptanucleotide pd(CCAAACA) as an example.

[Characteristics of immunologic and neuro-hormonal status in patients with neuroses]. / Osobennosti immunnogo i neirogormonal'nogo statusa bol'nykh nevrozami.

More than 3500 neurotic patients have been examined with emphasis on their immune status and functioning of the sympathoadrenal system (SAS) (determination of adrenaline, noradrenaline, dopamine and L-DOPA excretion in terms of their daily biorhythm). The comparison of the immune and neurohormonal data of neurotic patients indicated an obvious relation between the immune status and the type of SAS functioning. The high-risk group comprises patients with the adrenaline type of SAS functioning and pronounced adrenaline and noradrenaline hypersecretion, SAS hypofunction, and imbalance between the hormone-mediated and immunologic characteristics.