[Prognostic value of some spectral EEG indices in patients in acute period of brain supratentorial hemorrhagic stroke].
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Acute Disease↗
Biomedical subjects
D A Kuznetsov
Publications and source records attributed to D A Kuznetsov.
[Effects of medium-weight molecules isolated from plasma of healthy and burnt animals on the cellular composition of cultured bone marrow erythroblastic islets].
The so-called median-weight molecular fractions (M, B = 0.5-1.5 kDa) exerting a marked hemopoietic effect in the cultured bone marrow erythroblastic islets were isolated from the plasma deproteinates of healthy dogs and animals with acute inflammation (thermal skin burn) by Sephadex G-15 gel chromatography. Acute inflammation is attended by the occurrence of blood medium-weight molecular components that suppress erythropiesis and by the concurrent high rate of granulocytopoiesis in the cultured bone marrow erythroblastic islets. Medium-weight molecular fractions from the blood of healthy dogs substantially were found to suppress erythropoiesis and to stimulate granulocytopoiesis in the cultured erythroblastic islets.
Animals↗
[Comparative analysis of clinical computer electroencephalographic findings in patients with acute cerebral hemispheric and hemorrhagic stroke].
As many as 146 patients in the acute period of cerebral ischemic insult (CCI) and cerebral hemorrhagic insult (CHI) of hemispheric localization were examined. Clinical-and-neurological examination was done together with that computed-tomography (CT)-guided, computerized electroencephalography (CEEG), applied mathematical statistics. Polymorphous relation has been revealed between the clinical pattern of cerebral insult and CT/CEEG criteria. The strongest relation has come to be between the localization and clinical pattern of CCI, and between the size of the affected area and clinical patterns of CHI. Parameters of the EEG-pattern closely correlate with clinical patterns of insult.
Acute Disease↗
[Mapping of active site of alcohol dehydrogenase with low-molecular ligands].
In search of an active alcohol dehydrogenase inhibitor, the structure of which may serve as the basis for a potential drug design, the active site of alcohol dehydrogenase containing NAD and Zn2+ ions was mapped using the method of molecular mechanics. Molecular docking was performed using a number of ligands containing characteristic functional groups: formate ion, ammonia, ammonium ion, methanol, and methylamine. Sites of preferable binding were revealed for each ligand and arranged in order of decreasing energy of binding to the enzyme. A comparison of the predicted ligand-binding sites and the experimental data on the location of water and inhibitor binding sites in the known structures of corresponding alcohol dehydrogenase complexes indicated a coincidence of the complex formation sites, which confirms the validity of the method and provides the requirements for a highly effective inhibitor (the pharmacophore model).
Alcohol Dehydrogenase↗
Ribonuclease-charged vector for facile direct cloning with positive selection.
Plasmid vectors for positive selection of cloned inserts in Escherichia coli were devised, based on an expression plasmid (pMT416) for the bacterial ribonuclease barnase. In addition to the barnase gene under control of a synthetic tac promoter, these plasmids carry the gene for the barnase inhibitor, barstar, the constitutive expression of which protects the bacterium from the detrimental effects of moderate barnase production. Full expression of the barnase gene overcomes protection by barstar and becomes lethal. Having a unique SmaI/XmaI site in the barnase structural gene, pMT416 itself can be used as a selective vector: uncut or religated pMT416 will preclude growth while plasmids with inserts in the barnase gene will allow the cells to survive. The entire pUC polylinker was inserted into the barnase gene in place of the Val-36 codon. This insert of nineteen largely hydrophilic amino acids does not prevent the lethal effect of full expression of the gene. The resulting plasmid, pMT440, is a generally useful selective cloning vector representing the "kill-the-rest" approach.
Amino Acid Sequence↗
[Ribonuclease gene--a base of "zero background" cloning].
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Bacterial Proteins↗
A technique for identifying atoms from a screen image.
Improving the interfaces in molecular graphics applications, making them more natural and easy to use, is an important task, given the current complexity of the displayed objects and of modeling operations. Clicking near an atom center is the usual method of atom selection. However, this method has certain disadvantages when working with images composed of different atomic representations such as sticks, CPK, or dotted surfaces. We propose another technique allowing the user to obtain the correct answer when he or she clicks on any element of the atom image.
Algorithms↗
VisiCoor: a simple program for visualization of proteins.
A well-drawn picture acts as an excellent metaphor for something real, and human vision provides instant, random access to any part of which the picture represents. It is in this sense that pictures can convey information more effectively than words alone. The power of the graphics work-stations available today makes visual presentation of scientific results a reality. A molecular graphics program for investigating protein structures, as well as several sample plots that show the power of the program, are presented.
Computer Graphics↗
Minamata disease: what is a keystone of its molecular mechanism? A biochemical theory on the nature of methyl mercury neurotoxicity.
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Animals↗
The molecular mode of brain mRNA processing damage followed by the suppression of post-transcriptional poly(A) synthesis with cordycepin.
Complete suppression of polyadenylation of nuclear precursors of rat brain mRNA by cordycepin leads to degradation of some translatable sequences of both poly(A)(+)- and poly(A)- pre-mRNA localized in 80S hnRNP-particles. This fact has been established by comparative analysis of the data of two-dimensional gel-electrophoretic mapping of translation products synthesized in reticulocytic cell-free system using the exogenous purified templates of rapidly labelling translatable 9-17S hn RNA (pre-mRNA) isolated from brain 80S hn RNP particles of experimental (4 hrs after cordycepin injection) and control (injection of physiological solution) adult healthy male rats. Long contact of brain cells with cordycepin (4 or more hrs) creates conditions for formation of hnRNP-particles devoid of poly(A)+ RNA and poly(A)-binding proteins. These particles differ from "normal" ones by the value of the RNA/protein ratio, and by considerably lower resistance to the action of exogenous ribonucleases and endogenous RNase. Cordycepin does not have a direct effect on biosynthesis of nuclear poly(A)-binding proteins within the duration of the experiment (8 hrs). The phenomena described are discussed.
Animals↗
Lithium salts adopted for psychopharmacological use as the modulators of protein synthesis in the brain: analytical review.
The investigations of the effects of Lithium salts on protein synthesis activity with special reference to neurochemical aspects may provide a fruitful development of a system of safe and effective, psychopharmacological methods for treatment and prevention of the Lithium-curable mental disorders complicated by general neurological (neuropathological) symptoms.
Animals↗
Neurospecific translation control and the problem of potent danger of drugs and chemicals: a caution.
At present, chemicals are an integral part of the surrounding biosphere. A great number of new xenobiotics for industrial, pharmaceutical, agricultural, or mode-of-life daily use (perfumes, cosmetics, food additives, etc.) may play a role of a danger health hazards. These chemicals may be environmental pollutants and due to this circumstance they promote different ecological disorders including the several epidemic-like processes such as, for instance, Minamata disease (chronic alimentary poisoning with methyl mercury), etc. Also, these chemicals may be industrial hazards promoting the origin and development of various occupational diseases. Finally, the numerous side effects of multiple new drugs may serve as causes of a number of different health disorders. Briefly, we must agree that modern man exists in the world with such inalienable elements as the steadfast increase of chemical soiling of Earths biosphere. Naturally, human health protection in our "chemically soiled" world is very difficult by urgent task. As for the solving of this task, it may be reached only in the case of successful fundamental studies of mechanisms of toxic action of different classes of chemicals performed at different biological levels (systemic, organ/tissue, cellular and molecular levels of research). A separate and special population of modern health-hazardous chemicals is a group of agents which selectively suppress protein synthesis in mammalian cells and tissues due to the direct effect on the translation machinery elements or on the messenger RNA processing steps. The agents of this group ("translation blockers" or, the same but more broadly, "protein synthesis inhibitors" (PSI) usually are quite dangerous for human health since these substances inhibit the central molecular process of life, i.e., the synthesis of protein molecules. The small but important subclass of the PSI is represented by the agents with marked neurotropic properties, i.e., by the agents which are able to promote the effective inhibition of protein synthesis in the brain, while the same agents do not essentially influence the translation processes in the liver and all other organs of the animal (human) organism. The main aim of the present monograph is to review and analyze the data obtained recently in the course of biochemical research of several neurotropic PSI (methyl mercury, lithium salts). However, this is not the single aim of the book. Thus, besides this the present monograph deals with analysis of the general peculiarities of action of some non-neurotrophic inhibitors which are able, nevertheless, to direct a number of specific neurotrophic effects (Cordycepin, tRNA).(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
In vitro studies of interactions between frequent and unique mRNAs and cytoplasmic factors from brain tissue of several species of wild timber voles of northern Eurasia, Clethrionomys glareolus, Clethrionomys frater and Clethrionomys gapperi: a new criticism to a modern molecular-genetic concept of biological evolution.
As a result of the complex comparative neurochemical study of the translation machinery functioning in the brain cells of three conventionally "phylogenetically related" species of wild timber voles (Clethrionomys glareolus, Clethrionomys frater and Clethrionomys gapperi), it has been found that the cytoplasm of brain cells of the latter contain an oligonucleotide (oligoribonucleotide) factor(s) with mol. weight below 1.0 KD which is able completely and highly selectively to inhibit the translation directed by mRNA which are species-specific templates and which were isolated from analogical tissue (brain) of "closely related" organisms. This phenomenon was found for the first time using special Cell-Free Translation Systems (CFTS) of very different variants of their composition consisting of the following main components: Post-Mitochondrial Supernatant (PMS), total cytoplasmic poly(A)+ mRNA or a species-specific poly(A)+ mRNA isolated form the PMS by affinity chromatography on the columns with the anti-mRNA1-FAB-(CNBr)-Sepharose, or purified 9S or 11S globin or histone specific mRNAs, respectively, and, finally a few samples of the CFTS used contain the additions of high or low molecular weight cytosolic compounds isolated from S150 fraction by ultrafiltration on Diaflo UM2 membrane with an exclusion limit of 1.0 KD. All CFTs components listed were isolated separately from the brain tissue of each organism studied. A new complex way for construction and using of the CFTS leads to an adequately documented conclusion which suggested the existence of special, so far uncharacterized in detail, cytoplasmic oligoribonucleotide factor(s) for efficient blocking for the cytoplasmic expression of "evolutionally renovated part" of genome; i.e., these factors seem to be sufficiently powerful suppressors of the translation of every mRNA template if the latter is not usual for the cell type containing the cytoplasmic suppressors mentioned in the case of a "so-called" newly found (perhaps, due to spontaneous but nonlethal mutagenesis) genes expression at the level of mRNA functioning in the cytoplasm. All findings and ideas of the paper are under discussion.
Animals↗
Chemical-induced modulation of ATP and protein synthesis processed inside rat brain mitochondria.
Rates of ATP production and protein synthesis rates were simultaneously studied using the isolated rat brain mitochondria and different types of brain polysomes (total, free, microsomal and mitochondrial membrane-bound). Protein synthesis was measured using a special reticulocyte lysate cell-free incubation medium. Prior to incubation, the intact ("unbroken") mitochondria were pretreated by several xenobiotics and natural metabolic effectors. The mitochondria incubated without these additions were used as controls. Chemically-promoted inhibition of ATP systhesis correlated with a significant activation of protein synthesis directed by the mitochondrial membrane-bound polysomes. The induction of ATP synthesis leads to a marked suppression of mitochondrial translation. Application of the selective translation blockers do not influence the ATP formation inside the isolated mitochondria. In general, mitochondrial membrane-found polysomes isolated from the intact normal organella are least active as compared with other tested polysomal fractions while the releasing of polysomes from mitochondrial membranes by Triton X-100 leads to the essential increase of the activity of these separated translation mechanisms. The separation of polysomes from the microsomal membranes do not change the activity of the former. A possible molecular mechanism, interdependence and biological significance of the established phenomena are discussed.
Adenosine Triphosphate↗
Novel electrophoretic approach to study of poly(A)+RNA pool heterogeneity in different areas of human postmortem brain.
A simple method for fast fractionation of human postmortem brain total poly(A)+RNA has been developed. Guanidine thiocyanate extractable RNA was directly applied on the membranes of cellulose nitrate with immobilized oligo(dT) chains. After the electrophoresis in 35 mM tris-acetete buffer (pH 7.90) containing 10 mM EDTA and 35% formamide, the membranes were washed with the same buffer for removal of nonbinding poly(A)-lacking RNAs. Then, poly(A)+RNA fractions were selectively stained by 3,5-dimethylphenol in the presence of FeCl3 at pH 2.35. Finally, the resulting electrophorograms were scanned at 500 nm for quantitative evaluation of the data.
Brain↗
[Polyadenylate polymerase in the diagnosis of the early stages of chemical carcinogenesis].
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Animals↗
Modulation of membrane-associated protein synthesis in rat brain cells by the anti-oxidant 2-ethyl-6-methyl-3-oxypyridine.
Intraperitoneal injection of different amounts of 6-methyl-2-ethyl-3-oxypyridine (6M2E3OP) to 3- and 18-month-old rats led to significant reduction of translating activity in vitro of membrane-bound polysomes of rat brain cells, but nor of free polysomes. This was more marked in the case of endoplasmic membranes of 18-month-old animals than in these of 3-month-old ones. Separation of polysomes from membranes by Triton X-100 resulted in restoration of template activity to the level of free polysomes. Forty eight hours after intraperitoneal injection of 6M2E3OP to 3- and 18-month-old rats the substance was found, by HPLC, only in endoplasmatic reticulum membranes of brain cells, but not in their cytoplasm. The xenobiotic did not change the age-dependent ratio of free and membrane-bound brain polysomes. At the same time the substance significantly inhibited the mean rate of synthesis of the longest polypeptide chains (MW 28-42,000 daltons) in cells of old animals.
Animals↗
Homologous oxypiperidines as inhibitors of protein synthesis in vitro and ex vivo.
The antioxidant nitroxyl-2 (2,2,6,6-tetramethyl-4-oxypiperidine-1-oxyl) is an active inhibitor of protein synthesis both in vitro (rabbit reticulocyte lysate cell-free translation system) and ex vivo (mouse liver). Demethylated derivatives of this agent demonstrate a significantly lower inhibitory activity. There is a strong positive correlation between quantitative parameters of toxicity, the ex vivo and in vitro inhibitory effects on translation, and the total number of methyl groups per drug molecule.
Animals↗