[Have we exhausted the reserves in radiotherapy of small cell carcinoma of the lung?].
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Biomedical subjects
Publications and source records attributed to A V Lebedev.
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31P NMR chemical shifts of the selected mono- and oligonucleotide derivatives, including the compounds with P-N, P-C, P-S bonds and phosphite nucleotide analogues have been presented. The influence of substituents upon 31P chemical shifts has been discussed. The concrete examples of 31P chemical shifts data application in the field of nucleotide chemistry have been considered.
The properties of the Ca2+-pump system of platelet microsomes isolated without Ca2+-precipitating anions are studied. Passive Ca2+ binding to the microsomes takes place in a noncooperative manner with Kd = 0.7 microM. Half-maximal stimulation of ATP-dependent transport occurs at 0.4 microM Ca2+. The velocity of Ca2+ uptake, Ca2+ capacity and the level of phosphoprotein in platelet microsomes are significantly lower than in cardiac microsomes. Energization of platelet and muscle microsomes and activation of intact platelets result in opposite charge redistribution in hydrophobic regions of the membranes. It is concluded that these charge movements are caused by Ca2+ binding to and dissociation from nonpolar binding sites in the membranes.
The distribution of lipophilic anion of phenyldicarbaundecarborane (PCB-) between water phase and fragments of sarcoplasmic reticulum (SR) from skeletal muscle was studied, using a bilayer lipid membrane (BLM) as a selective electrode. Addition of ATP leads to an increase in PCB- binding to SR vesicles. The ATP effect is totally reversible only in the presence of both EGTA and A23187. Chlorides, in contrast with oxalate and phosphate, do not reduce the ATP-dependent PCB- binding. Oxalate decreases also the energy-dependent extrusion of protons from SR into the medium. Preliminary incubation of SR fragments with calcium gluconate leads to a decrease in PCB- binding. Addition of ATP to purified Ca2+-ATPase is coupled with a release of PCB- and calcium from the enzyme. It is suggested that ATP-dependent binding of PCB- to SR membranes reflects calcium incorporation into the hydrophobic region of Ca2+-ATPase molecules.
Nonathymidilate was synthesized containing the chromophore (dansyl) group linked to its 5'-phosphate. In the presence of this compound the polyadenilic acid molecules are split by the radiation (power density J greater than or equal to 70 MW/cm2) of a nitrogen laser, while under the same conditions poly(C) and poly(U) are hardly affected. This selective optically non-linear effect was predicted and is explained in terms of radiativeless transfer of two-quantum excitation of the chromophore which is fixed on poly(A) molecule due to the formation of the complementary complex with nonathymidilate.
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The diagnostic value of bronchologic procedures in identification of peripheral cancer of the lung versus tumor's size, endoscopic pattern of bronchial lesion and tumor position with respect to the root of the lung was assessed. Rigid endoscopes and bronchofibroscopes were used in 806 patients with peripheral lung cancer. Bronchoscopic diagnosis of cancer was morphologically confirmed in 64.9% (respiratory endoscope alone--51.3 +/- 3%; bronchofibroscope or combined use of both devices--71.9 +/- +/- 2%).
The action of lipid hydroperoxides (LH), which are primary products of lipid oxidation, on cation permeability through bilayer lipid membranes (BLM) and sarcoplasmic reticulum (SR) membranes was investigated. Bilayer lipid membranes prepared from unoxidized phosphatidyl choline (PC) plus cholesterol or from total phospholipids extracted from SR vesicles possessed low cation permeability. Lipid oxidation induced by Fe2+-ascorbate led to a sharp increase in the calcium current through the BLM and to a considerable increase in the concentration of LH products. Further spontaneous lipid oxidation to final products led to decrease of LH concentration and calcium current through the BLM. The Ca2+ conductivity of the BLM increased more strongly if Fe2+-ascorbate was added to both sides of the BLM. The LH-induced cation permeability decreased in the sequence Ca2+, Mg2+, Ba2+, Sr2+, K+, Rb+, Cs+, NH4+, Na+, Li+. This is similar to the order of cation permeability known as the biological row of permeability and holds for BLMs formed from various lipids. In addition, Fe2+-ascorbate induced calcium ion leakage from SR vesicles isolated from guinea pig heart or from rabbit white skeletal muscle. It is proposed that the lipid hydroperoxide molecules form the simplest channel in lipid membranes, providing the permeability for calcium and other divalent cations.
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The data are presented on fractionation of cardiac and skeletal muscle Ca2+-ATPase fragments obtained by trypsin and cyanobromide hydrolysis. Amino acid composition of Ca2+-ATPases isolated from the heart and skeletal muscles and of enzyme fragments is determined. The ionophoric properties of the intact enzyme and its fragments are studied. The low-molecular weight enzyme fragment decreases velocity and the level of Ca2+-accumulation by the vesicles of sarcoplasmic reticulum. It is suggested that an "ionphoric" fragment of muscle ATPase is able to form transmembrane Ca2+-selective channel in model lipid membranes.
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It has been demonstrated with the use of 31P NMR pulsed spectroscopy that the reaction of mesitoyl chloride (MsCOCl) both with terminal and internucleotide phosphate groups pA, d(MeOTr)TpT and dpTpT (Ac) proceeds in a quantitative fashion within less than 2 min at 0 degrees C with the respective mixed anhydrides being thereby formed. The anhydrides of phosphomonoesters are resistant, unlike those of phosphodiesters which may be readily split by water, alcohol or amine without the internucleotide bonds being broken. Treatment of poly(U) with an excess of MsCOCl leads to rapid cyclization followed by formation of phosphotriesters. A comparatively easy hydrolysis leads to partial cleavage and isomerization of internucleotide bonds. A similar treatment of UpC showed that about 20% of the internucleotide bonds are cleaved, the remaining UpC being a mixture of approximately equal amounts of 3'-5'- and 2'-5'-isomers.
The rate constants were estimated by phosphorus NMR spectroscopy for the reactions of alcohols (Tr-dT, 2-cyanoethanol) in pyridine with the main types of the reactive phosphorylating intermediates formed by treatment of pdT-Ac, pdTpdT-Ac, Tr-dTpdT-Ac, Tr-dTpdTpdT-Ac with 2, 4, 6-triisopropylbenzene-sulfonyl chloride (TPS): 1) B type derivatives with phosphomono ester (PME) group converted to a phosphoryl pyridinium residue; 2) C type derivatives with PME and phosphodiester (PDE) groups converted to trisubstituted pyrophosphate; 3) D type derivatives with PDE groups converted to tetrasubstituted pyrophosphate. The two latter types are partially present as cyclic intramolecular pyrophosphates Ci and Di. The reactivity of the intermediates decrease in the series B greater than Ci approximately Di greater than C approximately D. The Ci derivative of pdTpdT-Ac when obtained in dimethylformamide was found to be rather stable to hydrolysis and could be separated from the other dinucleotide derivatives by ion-exchange chromatography. The Arrhenius parameters of all steps of the conversion of PME group of pdT-Ac to B derivative and of the reaction of TPS with PDE group of dinucleoside phosphate Tr-dTpdT-Ac were measured.
An analysis of the results of bronchial tumor biopsy performed in 200 lung cancer patients is reported. Morphological verification proved feasible in 193 of 200 patients. Biopsy and puncturing of the tumor are found to be most advantageous technics for the material take during bronchoscopy. Contrary to biopsy, an efficiency of transbronchial puncturing is not affected by the character of tumor growth and its morphological structure. A combined use of biopsy and puncture makes it possible to increase the percentage of morphologically supported diagnosis of pulmonary cancer. Transbronchial puncturing is also an efficient maneuver for detection of cancer recurrence in the bronchial stump and a residual tumor after conservative therapy. Endoscopic signs of the peribronchial pattern of tumor growth are absolute indications to its puncture.
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The interaction of 3'-O-acetyldithymidilate (pdTpdT(Ac)), thymidine-3',5'-diphosphate (pdTp) and thymidine-3'-phenyl-phosphate-5'-phosphate (pdTpPh) with 2,4,6-triisopropylbenzene sulphonyl chloride (TPS) and N,N'-dicyclohexylcarbodiimide (DCC) in pyridine and dimethylformamide (DMF) was studied by pulsed NMR spectroscopy on phosphorus nuclei. Thymidine cyclic 3',5'-pyrophosphate and dimeric pyrophosphate derivatives were shown to be the main products of the reaction of pdTp with TPS and DCC. The former shows spin AB-system with the unusually large spin-spin coupling constant about 28Hz upfield to the signals of the dimeric pyrophosphates in NMR spectrum. Analogous spin AB-systems with large spin-spin coupling constants (up to 32 Hz) were observed in the spectra of the reaction mixtures of pdTpdT(Ac) with TPS or DCC and of pdTpPh with TPS. These spin AB-systems were ascribed to 3',5'-cyclic pyrophosphate derivatives of pdTpdT(Ac) and pdTpPh.
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