Suppressor hyperactivity in relation to allogeneic lymphocyte proliferation as a manifestation of T- T-cell interaction defects in systemic lupus erythematosus

Phytohemagglutinin-stimulated lymphocyte proliferation by con A-induced immunoregulatory cells has been estimated in patients with active systemic lupus erythematosus (SLE) treated with prednisolone. Using the combination of normal immunoregulatory cells and proliferating target cells from normal donors with immunoregulatory cells and target cells from SLE patients, it was shown that the response to immunoregulatory cells in target cells of SLE patients was impaired. This is confirmed by a slight inhibition of SLE target cell proliferation and the activating effect of immunoregulatory cells on the proliferation of "sick" targets. The data give evidence of impaired T-T-cell interaction that may be a possible mechanism of immunoregulatory defects in SLE. These disturbances can, probably, cause hyperreactivity of suppressor cells affecting normal lymphocyte proliferation. It was shown that theophylline was useful for the correction of these disorders.     

The structure of the aglycon of eremomycin--a new antibiotic of the polycyclic glycopeptide group

Eremomycin is shown to be a new representative of the group of polycyclic glycopeptides. By the amino acid composition it is close to vancomycin but by the structure of triphenoxytriaminotricarboxylic acid it differs from vancomycin. Monodechlorovancomycinic acid was detected in eremomycin. On the basis of the data obtained in studies on the amino acid sequence and the molecule functional groups the structural formula of eremomycin aglycon was assigned. It is demonstrated that the chlorine-containing phenylserine fragment of monodechlorovancomycin acid is located in the N-end region of the aglycon peptide chain.     

Effect of individual factors of the space environment on the abiogenic synthesis of nucleotides

Key role of thermal energy has been shown in abiogenic synthesis of natural nucleotides (deoxyadenosine and cytidine monophosphates) in a solid phase during phosphorylation of deoxyadenosine and cytidine at the board of the orbital station "Salute-7" (temperature from -50 to 65 degrees C, exposition for 13 months) and in laboratory experiments (temperature 65 degrees C, exposition from 8 days to 6 1/2 months). The results obtained are discussed in relation to possible contribution of thermal energy in processes of prebiological evolution on the lithosphere of the Primitive Earth and various cosmic bodies.     

Minor components from the carminomycin complex

Three components differing by their properties from the carminomycins described earlier were isolated from the carminomycin complex. Comparison of the IR and UV spectra, as well as chromatographic and physicochemical properties of 2 of them showed that they were dihydrocarminomycin and its aglycone or dihydrocarminomycinone, which was prepared earlier by synthesis. The third component was a chromophore belonging to 1,4,6-trihydroxyanthraquinone. Investigation of its IR spectrum, physicochemica properties and PMR spectrum showed it to be carboxymethylethylcarminomycinone identical to epsilon-rodomycinone. The data were confirmed by 13C-NMR spectrometry.     

Interaction of dNTP, pyrophosphate and their analogs with the dNTP-binding sites of E. coli DNA polymerase I Klenow fragment and human DNA polymerase alpha

The 3',5'-exonuclease center of the Klenow fragment of E. coli DNA polymerase I (FK) was selectively blocked by NaF. The latter was shown to forbid the binding of nucleotides and their analogs to the enzyme exonuclease center. In the presence of poly(dT).r(pA)10 template.primer complex and NaF, we observed AMP, ADP, ATP, PPi and dATP to be competitive inhibitors of the FK-catalyzed DNA polymerization. The interactions of the nucleotides with FK and human DNA polymerase alpha were compared to reveal similarity of binding to the DNA polymerizing centers. Structural components of dNTP and PPi playing key roles in forming complexes with pro- and eukaryotic DNA polymerases were identified.     

Changes in Acholeplasma laidlawii plasma membrane functions during development of resistance to ciprofloxacin and tetracycline]

The role of transport activity of Acholeplasma laidlawii plasmatic membrane in the development of resistance to ciprofloxacin and tetracycline was investigated. It was shown that one of the important steps of resistance development in acholeplasms is a complex of adaptation metabolic reactions providing limited antibiotic accumulation by the cells. In the case of ciprofloxacin resistance metabolism changes concerning transport systems took place before mutations in target genes. Development of tetracycline resistance of mollecutes after incubation in the medium with enhancing antibiotic concentrations and not connected with the presence of tet(M) determinant was demonstrated for the first time.     

Distribution of CCR5-delta 32 gene deletion across the Russian part of Eurasia

32-bp inactivating deletion in the β-chemokine receptor 5 (CCR5) gene, common in Nothern European populations, is associated with reduced HIV-1 transmission risk and delayed disease progression. We have studied the deletion distribution in many populations in Eurasia by polymerase chain reaction analysis of 531 DNA samples representing West and East Siberian, Central Asian, and Far Eastern parts of Russia. An unusually high frequency (11.1%) of the deleted variant in natives of West Siberia, of Finno-Ugrian descent, was observed. Furthermore, the deletion was infrequent in indigenous populations of Central Asia, East Siberia, the Russian Far East, and Canada. We conclude that the Δccr5 distribution is limited primarily to Europeans and related western Siberian Finno-Ugrian populations, with a sharp negative gradient toward the east along the territory of Russian Asia. Received: 22 December 1997 / Accepted: 24 March 1998     

Fingers-closing and other rapid conformational changes in DNA polymerase I (Klenow fragment) and their role in nucleotide selectivity

We have developed a FRET-based assay for the fingers-closing conformational transition that occurs when a binary complex of DNA polymerase I (Klenow fragment) with a primer-template binds a complementary dNTP and have used this and other fluorescence assays to place the fingers-closing step within the reaction pathway. Because the rate of fingers-closing was substantially faster than the rate of nucleotide incorporation measured in chemical quench experiments, fingers-closing cannot be the rate-limiting prechemistry step defined by earlier kinetic studies. Experiments using Ca (2+) instead of Mg (2+) as the metal cofactor suggest instead that the prechemistry step may involve a change in metal ion occupancy at the polymerase active site. The use of ribonucleotide substrates shows there is a base discriminating step that precedes fingers-closing. This earlier step, detected by 2-AP fluorescence, is promoted by complementary nucleotides (ribo- as well as deoxyribo-) but is blocked by mismatches. The complementary rNTP blocks the subsequent fingers-closing step. Thus, discrimination against rNTPs occurs during the transition from open to closed conformations, whereas selection against mismatched bases is initiated earlier in the pathway, in the open complex. Mismatched dNTPs accelerate DNA release from the polymerase, suggesting the existence of an early intermediate in which DNA binding is destabilized relative to the binary complex; this could correspond to a conformation that allows an incoming dNTP to preview the template base. The early kinetic checkpoints identified by this study provide an efficient mechanism for the rejection of mismatched bases and ribose sugars and thus enhance polymerase throughput.     

Population of the mosquitoes Culex pipiens molestus (Diptera: Culicidae) in dwellings of Lensk city

Culex pipiens molestus has been distributed in Siberia and the Russian Far East since 80s of XX century. In early 90s, C. p. molestus reached South Yakutia (Nerungri city), and nowadays it occurs in South-West Yakutia (Lensk city). The number of breeding places with larvae and pupae of mosquitoes was not numerous in Lensk; among 56 examined houses, the places with larvae and pupae mosquitoes were registered in seven houses, while the adult mosquitoes occurred in the majority of the houses. The occurrence of larvae varied from 12.5 to 33.3%, occurrence of adults-from 12.5 to 100%. The coefficient of variation of larvae in the samples was equal to 0.92, and adults had the following coefficients: 0.84 in the houses without basement; 0.92 in the houses with dry basements; 1.05 in the houses with pools in basements. This data are referred to the casual type, it means that the distribution of mosquitoes in space is dispersed. Imago spread actively in stone house of Lensk that provides mosquitoes with new places of breeding, and supports the stability of population in new areas.     

Hypothalamo-pituitary system controls the development of humoral immune response during prenatal ontogenesis in rats

We studied the influence of the neuroendocrine system on the development of humoral immune response to sheep erythrocytes in rat fetuses. The removal of brain in utero by decapitation of 18-day fetuses induced a fourfold increase in the number of antibody-forming cells in the liver, as compared to the unoperated fetuses. After the removal of the forebrain, including hypothalamus (encephalectomy), the number of antibody-forming cells was comparable to that in unoperated fetuses. The observed increase in the number of antibody-forming cells in the liver was not due to a disturbed migration of precursors of B-lymphocytes in the spleen, since their content in the spleen was also four times that in the encephalectomized and unoperated fetuses. The increased number of antibody-forming cells in decapitated fetuses could be due to an enhanced proliferative activity of the lymphocytes in the liver of these fetuses. It has been proposed that humoral immunity is controlled by the hypothalamo-pituitary-adrenal system already during prenatal development; the adrenocorticotropic hormone and glucocorticoids appear to be involved in this regulation.