[Network of plastic neurons capable of forming conditioned reflexes ("membrane" model of learning)]. Simple net neuronal model was suggested which was able to form the conditioning due to changes of the neuron excitability. The model was based on the following main concepts: (a) the conditioning formation should result in reduction of the firing threshold in the same neurons where the conditioning and reinforcement stimuli were converged, (b) neuron threshold may have only two possible states: initial and final ones, these were identical for all cells, the threshold may be changed only once from the initial value to the final one, (c) isomorphous relation may be introduced between some pair of arbitrary stimuli and some subset of the net neurons; any two pairs differing at least in one stimulus have unlike subsets of the convergent neurons. Stochastically organized neuronal net was used for analysis of the model. Considerable information capacity of the net gives the opportunity to consider that the conditioning formation is possible on the basis of the nervous cells. The efficienty of the model turn out to be comparable with the well known models where the conditioning formation was due to the modification of the synapses.


[Thermogravimetric study of the stability of DNA hydrate]. Thermograviometric study of DNA hydrate in the temperature range 0--120 degrees C was carried out. The three-stage hydration was observed: the first stage within 20--32 degrees C, the second--70--95 degrees C and the third one--105--116 degrees C. An assumption is advanced concerning the nature of structural rearrangements related to the loss of water in the system DNA--water. High sensitivity of thermograviometry to initial water content in DNA hydrate was shown.


[Effect of luminescence quenchers on the maximum concentration of radicals in proteins following UV-irradiation (77 K)]. It has been shown that the limiting number of ionization acts (z) in a protein molecule in water solution UV-irradiated at 77 K is in proportion to the molecular weight: z=8.10(-6) M. Only one ionization is possible in simple protein with M=12,5.10(4). Radicals formed after one ionization protect from the effects of UV-radiation 60--150 adjacent residues of aromatic amino acids depending on their density in protein. Presence of the acceptors of excitation energy of aromatics residues (heme, eosin) results in a sharp decrease of limiting concentration of radicals in protein.


Study of nuclear mannosyl-transferase: lipids intermediates. Mannosyl-transferase of rat liver nuclei catalyzed the transfer of mannose, from GDP-mannose, to endogeneous lipids and proteins. Two solubility-different glycolipids were characterized: a mannosyl-phosphoryl-dolichol and an oligosaccharide-lipid. The labeling of the two lipids was consistent with a role in mannose transfer to nuclear glycoproteins, but not according to the Lennarz' scheme.


[Specific splitting of alpha-tropomyosin at cysteine-190 and a physico-chemical study of the fragments]. alpha-tropomyosin from rabbit spine muscle specifically cleaves at cystein-190. A study has been made of the physico-chemical parameters of the fragments resulting from the cleavage. The distortion of their structure by the cleavage is not great. The N- and C-end fragment are able to form a complex with an association constant of 5.10(4) M(-1). It is shown electrophoretically that troponin binds with the fragments only in the case when both fragments are present in the solution.


The growth of heart cells in culture. Evidences for a multiple activation of the pleiotypic program. Each medium renewal of confluent primary heart cell cultures derived from new born rats induces a pleiotypic response which leads to active proliferation. The presence of serum in the culture medium is essential for this activation of growth. Nutrient starvation prior to the activation decreases the response of the cells to serum. Serum starvation prior to the activation increases the serum dependence of the incorporation of labelled leucine but leaves the serum dependence of DNA synthesis unchanged. Ageing in culture decreases the serum dependence of the incorporation of labelled thymidine and amino acids but maintains it for alpha amino isobutyric acid transport. Several active components in human serum were distinguished by fractionated dialysis. A single dialyzable component stimulates both thymidine and amino acid incorporations. The transport of 2 deoxy-D-glucose is activated by another rapidly dialyzing component. The activation of alpha amino isobutyric acid transport may result from several components that are distanct from the previous ones. These results imply that a multiplicity of controls underly the pleiotypic activation of heart cell cultures by medium changes.


[Study of the structure and aggregation of histones. II. Structure of oligomers forming in mixed solutions of histones H2A and H4]. A change of light-scattering and sedimentation constant of histones H2A and H4 of monomers and oligomers has been studied. It has been shown that in salt-free solution the histone monomers are present. There is a mixture of oligomers (H2A)3, S20,w = 3,8S; (H2A)-(H4)1, S20,w = 3,8S; (H4)60, S20,w = 27S in the solution 0,6 M NaCl depending on fractions correlation. It has been shown that the molecules interactions in the composition of oligomers are cooperative and the cross interactions block the histone H4 self-aggregation.


[Molecular computer. Biological physics and physics of the real world]. Any mind (man or computer) using Physical laws is a part of physical world, and thus it is necessary to correct physical laws for taking into account influence of the work of real limited computer on the predicted result. If we suppose that univerce was constructed to be supreme regular for mind, then this correction is negligible and on principle there is possibility to calculate relation between fundamental physical and biophysical constants. Two main principle are proposed: 1. The principle of minimum action and uncontrole influence of mind. 2. The maximum asymmetry of elementary particles, which are allowed by first principle. The first principle requires the upper and the lower limits for all physical values, and first of all the upper limit for velocity (c) and the lower limit for action (h). The second principle allows to construct the minimal physical elements for mind.


[Theory of the behavior of macromolecules incorporated into liquid crystals]. The theory of macromolecules' interactions introduced into nematic liquid crystals is described. Formulas are obtained for the energy of the interaction of molecules of asymptotically large distances. Interaction between helical molecules is considered. The changes of interaction under the superposition of outer constant magnetic field is described. Formulas are obtained which describe the movement of macromolecules in a nonhomogenous medium.


Glucose transport by horse kidney brush borders. I.--Transport properties of brush border membrane closed vesicles. Brush border membranes isolated from horse kidney cortex as closed right-side out vesicles show selective permeability when analyzed on sucrose and dextran gradients. These vesicles can actively accumulate D-glucose. The preservation of the glucose transport system is demonstrated by the following features: (a) the uptake and release rates of D-glucose are higher in the presence of a sodium gradient, showing that D-glucose transport is a sodium-dependent process; (b) this transport, specific for the D-isomer, is inhibited by phlorizin; (c) the D-glucose transport system is saturable; (d) no inhibition of D-glucose transport is found with C-mannose; (e) the D-glucose uptake is sensitive to osmotic variations.


[Polycytidylic matrix complex formation with complementary and noncomplementary purine nucleoside triphosphates]. Misincorportion into I poly(C) : I GTP complex, alpha = (formula: see text), has been determined by using H3-ATP. At ATP total concentration increasing from 6X10(-6) M to 4.5X10(-3) M the alpha value increases going asymptotically onto a plateau. The maximum misincorporation in the studied conditions is I adenilic resiude per congruent to 1400 guanilic ones. No ATP incorporation into the 2 poly(C) : I GTP complex was found. It is shown that misincorporation in non-enzymic recognition is essentially determined both by the difference in complementary and non-complementary monomer stacking and by the difference in their binding with the polynucleotide template.


[32P incorporation into phospholipids of EHSVi transformed fibroblasts, with regard to adherence to the support]. The rate of 32P incorporation into phospholipids of EHSVi transformed fibroblasts was studied by pulse experiments (2 hours) in cells which are detached from the support by trypsin and either maintained in suspension or replated and in the process of adhering. This is performed comparatively to cells in monolayers. Cells are taken during or after the log phase. Both global incorporation into phospholipids and, in the case of cells in log phase, percentage of incorporation into phosphatidylinositol are lowered, after detachment from the support, in suspended cells. They are stimulated by a new contact with the support. In the same conditions, percentages of incorporation into phosphatidylethanolamine and phosphatidylcholine remain at values they have in cells in monolayers. These values are characteristic of the physiological state of cells in monolayers, in relation with medium factors exhaustion.


[Modification of retinal photoreceptor membranes and Ca ion binding]. Calcium binding by modified photoreceptor membranes of cattle retina has been studied. Ca2+-binding the membranes significantly changes after C-phospholipase treatment, displaying the initial growth (less than 65% of lipid phosphorus removed) with subsequent decrease (more than 65% of phosphorus removed). Liposomes of the photoreceptor membranes lipids were found to bind more calcium than do the native photoreceptor membranes. Proteolytic enzymes (papaine, pronase) splitting some rhodopsin fragments do not affect the ability of the membrane to bind Ca2+. The increase of light-induced Ca-binding is observed only after the outer segments preincubation under conditions providing for rhodopsin phosphorylation. This effect was observed also after the splitting of the rhodopsin fragment by papaine. It is concluded that calcium binding in the photoreceptor membranes is mainly due to the phosphate groups of phospholipids.


[Protein composition of fragmented rat liver chromatin during postnatal ontogenesis]. It was shown that after treatment by Ca2+- and Mg2+-dependent DNAses and subsequent dosed ultrasonication the fractions of active and relatively inactive chromatins isolated from liver cell nuclei of rats differing in age contain all main types of histones, but differ considerably in the relative amounts of individual fractions of these proteins. In all age groups studied the proteins of relatively inactive chromatin are largely histones, while the amount of non-histone proteins is higher in active chromatin. In the course of postnatal development the amount of histones in both chromatin fractions is increased and that of non-histone proteins is decreased. This is probably due to heterochromatization of the chromatin complex in liver cells with ageing. In the course of postnatal ontogenesis the spectrum of non-histone proteins in both chromatin fractions is changed.


[Study of different conformational states of transketolase by the method of perturbation UV-spectrophotometry]. The conformational parameters of apotransketolase, holotransketolase and the enzyme-substrate complex were studied using colvent perturbation technique, a 20% solution of dimethyl sulfoxide being used as perturbant. The apoenzyme was found to contain 4--5 tryptophane residues and 12--14 tyrosine residues accessible for the solvent. The amount of the residues is reduced nearly 2-fold after formation of the holoenzyme. In the enzyme-substrate complex the amount of tryptophane and tyrosine residues accessible for the solvent is increased up to the inital value. The changes in the conformational states of the active site of apoenzyme, holoenzyme and the enzyme-substrate complex are discussed.


[Relationship between the ganglioside composition of Ehrlich ascitic carcinoma and cell population density]. The ganglioside composition of Ehrlich ascite carcinoma cells changes drastically with changes in density of the cell population. Upon 30-fold dilution of the native cell suspension and subsequent incubation for 2 h the amount of total gangliosides per cell doubles the quantities of a monosialoganglioside and of a disialoganglioside increase ten- and five-fold, respectively, whereas the other cell gangliosides do not change. The decrease of cell density is supposed to be accompanied by induction on the cell surface of a sialytransferase activity, which appears to be depressed in the dense suspension.


[Biospecific chromatography of poly(A)-containing RNA on poly(U)-Sepharose]. It is shown that in addition to specific binding of polyadenylic sequence with poly(U), the chromatography of poly(A)-containing RNAs on poly(U)-Sepharose is accompanied by nonspecific irreversible adsorption of polynucleotides on Sepharose gel. This disadvantage may be overcome by establishing optimal BrCN/Sepharose rations during Sepharose activation and by many-fold treatment of poly(U)-Sepharose with ethanolamine immediately before chromatography of RNAs. It was also found that the efficient separation of poly(A+)-RNA preparations from poly(A-)-RNAs is achieved only after double chromatography of RNA on poly(U)-Sepharose. The amount of poly(A+)-RNA in total RNA preparations isolated from bound polyribosomes of 10-day-old chick embryos is equal to 1%. Data from PAAG gel electrophoresis are indicative of the lack of degradation and high heterogeneity of the preparations under study.


[Nuclease activity of the cytoplasmic ribosomes of hepatocytes and several experimental hepatomas]. The nuclease activities of proteins, constituents of cytoplasmic ribosomes obtained from normal liver rats (Wistar) and C3HA mice as well as from hepatomas (both solid and ascites forms) transplanted into the above animals, were studied. RNA in membrane-bound ribosomes of normal rat liver incubated at 37 degrees C undergoes endogeneous hydrolysis resulting in formation, apart from acid-soluble products, of 6S, 8S and 11S fragments comprising 15 to 20% of the original amount of RNA. In contrast, in hepatoma membrane-bound ribosomes RNA treated likewisely remains intact. The proteins responsible for the RNase activity isolated from ribosomes were subsequently fractionated using ammonium sulfate and chromatography on DEAE-Sephadex columns and their properties were studied. The RNase activity completely disappeared from the membrane-bound ribosomes of Zajdela, 27 rat hepatomas and Guelstein hepatoma 22A, but not from the slow growing Guelstein hepatoma 48.


[Localization of (3H)hydrocortisone in rat liver nuclei]. The content of hydrocortisone in rat liver nuclei reaches its maximum in 1 hour after its intravenous injection and remains stable for another hour. In three hours after introduction it falls to the initial level (15 min after the injection of [3H]hydrocortisone). The accumulation of the hormone in nuclei completely coincides with kinetics of reversible DNA supermethylation and correlates with the induction of transcription. No free [3H]hydrocortisone was found in nuclei, in isolated nuclei it is found in the fraction of nuclear membranes, nucleoplasma, nucleolus and chromatin. Specific radioactivity of [3H]hydrocortisone (d. p. m. per 1 mg of DNA) in active chromatin is 10--50-fold as high as in condensed chromatin and is 10--15-fold as high as in nucleolus. It is suggested that there are at least two types of binding hormonereceptor complexes with chromatin. The initial binding of these complexes with condensed chromatin may result in its structural rearrangement (euchromatization), in the appearance of more specific secondary sites for binding hormone-receptor complexes with chromatin DNA, and also in the appearance of methylation and transcription initiation sites in DNA.


[Free amino acid concentration in the tissues of rats with different forms of thiamine deficiency]. The levels of free amino acids in rat tissues under thiamine deficiency induced by antivitamin (oxithiamine) and under thiamine-deficient diet were studied. Changes in the amino acid pool at these two forms of vitamin B1 deficiency were revealed. The most typical change consists in extensive accumulation of alanine and glutamate with a simultaneous decrease in the amount of many other essential and non-essential amino acids. The disturbances in the amino acid pool under thiamine deficiency may be probably regarded as resulting from inhibition of alpha-keto acid dehydrogenase activities.


[Effect of the structure of the nucleoside ligand of cobalamines on their enzymatic properties in a glycerol dehydratase system]. The interaction between 8 adenosyl cobalamine (AdoCbl) analogs modified in adenine and deoxyribose of the nucleoside ligand and glycerol dehydratase from Klebsiella pneumoniae ATCC 25955 was studied. It was found that araadenosyl-, 3-isoadenosyl-, aristeromycyl- and nebularyl cobalamines possess coenzymic properties. The catalytic activities of these analogs complexes with glycerol dehydratase make up to 110, 36, 30 and 6% of the enzyme activity with the natural cofactor AdoCbl. Benzimidazolribosyl-, toyokamycil-, L-adenosyl- and adenosylethyl cobalamines are effective competitive inhibitors with respect to AdoCbl. All AdoCbl analogs have high affinity for the apoenzyme; their Km and Ki values are close to 10(-7)--10(-8) M. The inactivation kinetics of catalytically active glycerol dehydratase complexes in the absence of substrate were studied. The rate of this process was found to depend on the structure of the analogs. It was shown that inversion of the 2'-OH-group of deoxyribose in AdoCbl results in the increase of Km for the substrate (1,2-propanediol). The main parameters of the CD spectra for AdoCbl analogs are described.


[Tissue-specific decrease and change in the character of DNA methylation in cattle with aging]. The content of 5-methylcytosine (m5C) in DNA of different cow organs is found to decrease in ontogenesis. No other age changes were found in DNA structure and molecular population (GC content, the content of different in the length and the base composition pyrimidine clusters, hyperchromicity value etc.). It is suggested that the age tissue-specific decrease of the m5C content is due to a decrease of the level of DNA methylation, which takes place in heart, kidneys, spleen and brain DNAs and is not observed in lungs. Maximal level of DNA methylation was observed at embryogenesis, when the m5C content in heart DNA decreases (from 1.8 to 1.4 mol. %), then it remains stable up to 1 year old and then sharply decreases with age and reaches 0.94 mol. % at the age of 10 years. The m5C content in liver DNA decreases (from 1.6 to 1.2 mol. %) at the end of embryogenesis and then it does not change. A pronounced decrease of the m5C content was  observed in DNAs of cerebral hemispheres, cerebellum, hyppocampus, neurohypophysis and thymus. The decrease of m5C content in thymus DNA is non-random, it concerns only Pu-m5C-Pu, but not long pyrimidine clusters Pu-Pyn-Pu (n greater than or equal to 2). Tissue-specific decrease and the change in pattern of DNA methylation observed are suggested to be a possible mechanism for the age change (distortion) of transcription and cell functioning.


[Bioelectrochemical oxidation of formate]. The process of electrochemical oxidation of formate on a coal electrode with the help of a two-enzyme system composed of NAD-dependent formate dehydrogenase and NADH-dehydrogenase, catalysing oxidation of NADH with reduction of methylviologen was studied. In this system the oxidation of formate proceeds in the diffusion regime. Under experimental conditions the value of current density at a potential higher than +0,2 V and at the rotating rate of 600 rpm is 12 mA/cm2. The results obtained show that NAD-depend dehydrogenases can be used for electrochemical oxidation of organic compounds which are their substrates.


[Alliinase: purification and chief physico-chemical properties]. A method has been developed for the purification of alliinase from garlic bulbs. High purity preparations of the enzyme were obtained with specific activity increased 67-fold over that of the homogenate. The preparations were homogeneous on electrophoresis in polyacril gel. Total activity yield was 25%. The native enzyme has a molecular weight of 130.000 and consists of two subunits. Approximately 6 moles of firmly bound pyridoxal phosphate are determined per 1 mole of the purest enzyme (4 equivalents are apparently bound non-specifically outside the active sites). The isoelectric point (pI) of alliinase in 6.2. The enzyme's absorption and circular dichroism spectra have one maximum at 430 nm, in the characteristic range of many pyridoxal-P-containing enzymes. The Km value for the natural substrate, alliin, is 5 . 10(-4) M.


[Reaction between adenosine-5'-chloromethylphosphonate and the allosteric center of phosphorylase B]. The interaction between phosphorylase B and an AMP analog, adenosine-5'-chloromethylphosphonate, is found to be irreversible. Their binding stechiometry is calculated from the differential absorption spectrum. Maximal inhibition is reached when 1,3--1,5 moles of the analogue is bound per mole of monomer phosphorylase B. The enzyme-inhibitory complex exhibited 50% activity is characterized by a sigmoid curve of the reaction rate dependency on the substrate concentration, by a decrease of the affinity to glucose-1-phosphate and the maximal rate, and by an increase of Hill's coefficient. Similar SH-groups titration curves were obtained for modified and native phosphorylase in the presence of AMP. Apophosphorylase was incapable of the complete reactivation by pyridoxalphosphate in the presence of adenosine-5'-chloromethylphosphonate. The complex of phosphorylase B and the AMP analogue is found to be inhibited by glucose-6-phosphate, like the native enzyme in the presence of AMP. The results of ultracentrifugation and disc electrophoresis show that the AMP analogue contributes the formation of the tetrameric form of the enzyme. The data obtained indicate the tight binding of adenosine-5'-chloromethylphosphonate in the active site of phosphorylase B. The properties of the complex confirm the importance of the phosphate group for the AMP binding in the allosteric site and for the enzyme activation.


[Modification of drug oxidation in rat liver microsomal fractions by mitochondria]. In order to establish possible interaction between mitochondrial membranes and endoplasmic reticulum, the effects of succinate, fumarate and malate (10(-6)--10(-2) M) on N-demethylation of ethylmorphine in liver homogenate, liver homogenate, enriched by mitochondria and in liver sections of newborn animals were studied. In experiments with liver homogenate and liver mitochondria-enriched homogenate the substrates exerted no effect. Addition of mitochondria decreased the homogenate activity by 50%, when NADPH was used as cosubstrate. Studies on liver sections showed the increase of activity only in case of succinate. The activity of liver sections from newborn rate was 30% of that from adult animals. The enzyme activity was suppressed by the Krebs cycle substrates.


[Interaction between sodium bisulfite and bacteriophage SD DNA]. The interaction between sodium bisulfite and the cytosine residues within the intraphage DNA of phage SD was studied to elucidate the structure of viral nucleoprotein. Hydrolysis with perchloric acid of bisulfite-modified phage SD results in 18% decrease of cytosine and appearance of products having the properties of cytosyl amino acids (most probably cytosyl lysine). When the modified phage before hydrolysis was subjected to mild destruction in 0.1--1 M NaCl or Tris-HCl buffer (pH 7.0), neither the decrease of cytosine nor the appearance of cytosyl peptides was observed. However, these results were observed when the phage was heated at 70 degrees C in a medium containing 0.05 M phosphate buffer, pH 7.9--8.5. The presence of cytosyl amino acids in the modified phage, representing nucleotide-protein covalent cross-links explains the results of viscosometry and centrifugation in CS2SO4 density gradient. It is assumed that the bisulfite reaction with cytosine within phage SD is completed at the stage of intermediate product formation, i.e. C5--C6-dihydro-C6-sulfopyrimidine, in which the amino group is screened by interaction with protein (product VII). This product may exist only in situ; when the phage nucleoprotein is destroyed in phsophate-free media, product VII is converted into original cytosine. Under acidic hydrolysis or in the presence of phosphate ions under heating, product VII undergoes transamination accompanied by SO3 split-off and reconstitution of C5--C6 double bond to form cytosylamino acids.


[Effect of phase transitions in microsomal membranes on energetic characteristics of oxidation]. Naphthalene and aniline oxidation by intact and induced enzyme systems of rat liver microsomes, NADPH and O2 has been studied in a broad temperature range. The oxidation of the same substrates has also been studied in the systems "microsomes--cumene hydroperoxide" and "purified cytochrome P-450--cumene hydroperoxide". The temperature curves of catalytic constants for type I substrate (naphthalene-oxidation) in the system with cofactors is characterized by break on Arrenius dependence near 18--24 degrees C and explained by phase transitions of microsomal membrane lipids. The temperature curves of catalytic constants for type II substrate (aniline-oxidation) in all studied systems do not break on Arrenius plots. Catalytic oxidation contants of both substrates in systems "microsomes--hydroperoxide" and "cytochrome P-450--hydroperoxide" are characterized by constant activation energies in broad temperature range. The results obtained are discussed from the point of view of the effect of phospholipids phase transitions in microsomal membrane on a rate limiting step.


[Isolation and some properties of transketolase from rat liver]. A new procedure transketolase isolation from rat liver using sievorptive chromatography and adsoption chromatography on hydroxylapatite is described. An enzyme preparation is obtained, which is homogenous under polyacrylamide gel electrophoresis. Molecular weight of native enzyme, estimated by sedimentation equilibrium method, is 130 000. Electrophoresis in polyacrylamide gel in the presence of sodiumdodecylsulphate has revealed a single protein fraction with molecular weight of 70 000. The extinction coefficient A1%1cm at 280 nm is found to be 13. Thiamine pyrophosphate content in native holoenzyme is 1.8--2 moles per 1 mole of protein.


[Biosynthesis of NADP-malate dehydrogenases in greening etiolated maize leaves]. The activities of NADP-dependent malate dehydrogenases in greening etiolated maize leaves were studied. "Malic" enzyme (EC 1.1.1.40) in bundle sheath cells developed slower as compared to NADP-malate dehydrogenase synthesizing malic acid in mesophyll chloroplasts. The increase in "malic" enzyme activity in the light was suppressed by protein synthesis inhibitors--chloramphenicol and cycloheximide. Possible localization of enzyme protein synthesis is discussed.


[Replication and reassociation kinetics of nuclear matrix DNA from regenerating rat liver]. Fraction 1, containing 65--70% of nuclear DNA (nDNA) was extracted from isolated rat liver nuclei. Then nuclear matrix fraction, containing 30--35% of nDNA was extracted with 1.2 M NaCl. About 1% of nDNA war discovered in residual matrix. Specific activity of residual matrix labelled DNA within 1 and 3 min. after the injection of 14C-orotic acid into the liver portal vein (24 hours after hepatectomy) was respectively in 70 and 50 times higher, and that of matrix DNA--in 45 and 20 times as high as in fraction 1 DNA. Thus, replication begins from nuclear matrix DNA. The latter is enriched with unique sequences by 10%, as compared with total nDNA, and its reassociation kinetics does not change at different stages of the cell cycle (0 and 24 hours after partial hepatectomy). It is suggested, that DNA does not migrate with respect to nuclear matrix under replication.


[Some features of rhodopsin regeneration process in the presence of exogenous 11Z-retinal in teleosts]. The rate of rhodopsin regeneration in decolorized rod outer segments ROS of pollock and ruff in the presence of exogenous 11Z-retinal is found to depend slightly on the temperature. The Arrhenius curve is linear within 0--20 degrees C and 0--30 degrees C in case of pollock and black ruff ROS respectively. The increase of the regeneration temperature above the upper limit results in both cases in the decrease of the chromophore binding rate due to the temperature denaturation of fish opsin. The rate of opsin regeneration in bovine ROS is temperature-dependent within 0--50 degrees C, the Arrhenius curves having a specific break with the temperature conversion at 12--13 degrees, which indicates a different 11Z-retinal binding rate with bovine opsin at low and high temperatures. Maximal rhodopsin regeneration temperature was observed within 5--10 min. for fish ROS and 1.5 hour for bovine ROS. Trimethylcyclohexene derivatives with a side chain of about 7 carbon atoms and 13Z-retinal competitively inhibited the rhodopsin regeneration in pollock and bovine ROS, while 13E-11, 12-dehydroretinal and all-E-retinal did not effect this process. Some peculiarities of the rhodopsin regeneration process in fish are discussed in connection with the molecular organization of a lipid phase of photoreceptor membrane and chromophore-binding region.


[Molecular weight distribution of hydrolysis products of polyuridylic acid by cobra venom ribonuclease. Preparation of polynucleotides of required molecular weight]. The composition of polyuridilic acid hydrolisis products with mol. weight 400.000--600.000 by endoribonuclease from cobra venom was studied. The molecular weight distribution of products formed at initial stages of hydrolysis was according to the regularities of accidental cleavage of phosphodiether linkages. The sufficient non-statistic regularities due to the high-molecular polynucleotide hydrolysis for the most part during further hydrolysis were observed out of the way of accumulation of oligonucleotides with a polymerity degree of about 15--20. As shown from the oligocytidilates hydrolysis, the velocity of process increased sufficiently with increasing substrate polymerity degree. The results obtained were used for preparation of polyuridilic fractions with a narrow range of molecular weight distribution.


[Role of guanidine groups of glutamate dehydrogenase arginine residues in the binding of sex hormones]. Interaction of sex hormones and glutamate dehydrogenase is studied in vitro. Data are presented concerning the participation of guanidine groups of the enzyme arginine residues in the binding of sex hormones and in the realization of their inhibitory effect.


[Resolution of beta-cyanoalanine synthase and recombination of its apoenzyme with pyridoxal-5'-phosphate and its analogs]. A procedure is described for the resolution of beta-cyanoalanine synthase (E.C.4.4.1.9) from blue lupine seedlings. It includes total inhibition of the enzyme the hydroxylamine (10(-2) M) followed by separation of coenzyme oxime from the protein on Sephadex G-25. Conditions for maximal apoenzyme stabilization and reactivation (nature, concentration and pH of the buffer, coenzyme concentration, etc.) were studied. The extent of apoenzyme reactivation by pyridoxal phosphate is found not to depend on the nature of the buffer (pH within the range from 7,1 to 8,8) in the preincubation medium. The interaction were investigated of cyanoalanine aposynthase with pyridoxal phosphate analogues substituted in positions 2,3,4,5 and 6 of the pyridine ring. Only 6-methyl-, 2-nor- and 5'-methyl-pyridoxal phosphate were found to activate apoenzyme to the extention 100, 56 and 31% respectively under the assay conditions. The other analogues tested do not activate apoenzyme, but they mostly interact in the enzyme's active site, competitively inhibiting the binding of pyridoxal phosphate. Ki values were determined for some analogues (according to Dixon). It is found that slight changes in structure of the coenzyme molecule markedly decrease of affinity of the analogue to cyanoalanine aposynthase. As compared with other pyridoxal-phosphate-containing enzymes, this synthase, like serine sulphhydrase and cystationine synthase, has more stringent requirement as to coenzyme structure.


[Role of Ca-specific binding sites in the induction of conformational changes in troponin structure]. A new technique for the registration of troponin conformational changes by hydrophobic fluorescent dye, dimethylnaphteirodin, is described. The increase of Ca2+ concentration from pCa 8 to pCa 5 is accompanied by 4--5-fold increase of fluorescence of troponin--dimethylnaphteirodin complex and by the shift of the fluorescence maximum by 10 nm into the short-wave region. Isolated troponin components and troponin I--troponin T and troponin I--troponin C complexes do not bind dimethylnaphteirodin. The troponin T--TROPONIN C complex binds dimethylnaphteirodin, and fluorescence of the bound dye increases under the increase of Ca2+ concentration, as it does in the case of complete froponin complex. The apparent Ca2+-binding constant by the whole troponin complex (K=8.10(6) M(-1)) and by troponin T--troponin C complex (K=8.10(5) M(-1)), and the value of fluorescence of troponin- and troponin components-bound dimethylnaphteirodin do not depend on the magnesium concentration. Highly cooperative dependence of the fluorescence intensity of troponin-dimethylnaphteirodin on Ca2+ concentration (the Hill coefficient is 2.0--2.4) suggests, that the changes in the troponin structure, registered using dimethylnaphteirodin, take place only after Ca2+ binding to two Ca-specific sites.


[Effect of chemical modification of the surface of erythrocytes on their stability to the hemolytic action of sodium alkyl sulfates]. The hemolytic action of a homologous series of sodium alkyl sulfates (C8 to C15) on dog and human erythrocytes was measured. The influence of trypsin, pronase and neuraminidase treatments on the lytic resistance of human red cells was studied. A new approach evaluating the hemolytic activity of ionic surfactants is expressed as a ratio of a concentration providing 50% lysis to its CMC-value. The results obtained are examined for their bearing on the use of surfactants as a means to study the structure organization of biological membranes.


[Nuclear and cytoplasmic ribonucleoprotein complexes of normal mouse liver cells, Guelstein hepatomas 22A and 48 and of liver of tumor-bearing animals]. Nuclear and cytoplasmic RNP complexes obtained from normal mouse liver cells, Guelstein hepatomas of different degrees of malignancy (22A and 48) as well as from liver of tumor-bearing mice were subjected to chromatography on a celite column (NPC--chromatography). In addition cytoplasmic RNP complexes were centrifuged in sucrose and CsCl density gradients. The results of the NPC-chromatography indicate that nuclear rapidly labelled RNA species of all tissues under study are constituents of the two main types of RNP particles differing from each other by the tightness of RNA-protein bonds. No precursor-product relationship could be revealed between the above types of RNP-particles of nucleus, labelled under conditions of a partial Actinomycin D block. Rapidly labelled nonribosomal cytoplasmic RNAs represent constituents of RNP-particles resembling nuclear ones in their degree of heterogeneity and chromatographic position. Sedimentation analysis of cytoplasmic RNP-particles from tumours showed an increase in relative proportion of monoribosomes and informosomes (free non-ribosomal cytosol RNP-complexes) at the expense of polyribosomes and mRNP complexes. Thus, the liver cells of experimental tumour-bearing animals undergo changes (although not very well-defined), typical for tumour cells.


Size and shape analysis of schistomsome egg-counts in Egyptian autopsy data. We study egg-counts from a series of Egyptian autopsy cases with active schistosomiasis at death (Kamel, Cheever, Elwi, Mosimann and Danner 1977). The data are unique, and enable us to study the proportional distribution of eggs among various organs in relation to infection intensity for two species of schistosome worms. We develop a model for the distribution of eggs in three organs of the mesenteric circulation. Under a lognormal distribution assumption, several exact statistical procedures are presented and used to examine model consistency as well as isometry with respect to geometric means. Mesenteric egg counts for both Schistosoma mansoni and S. haematobium behave consistently with the model, and show little or no departure from isometry in cases without Symmers' fibrosis of the liver. We show that cases with Symmers' fibrosis have relatively more S. mansoni eggs in the small, as opposed to large, intestine. In the genito-urinary organs we show that the proportion of S. haematobium eggs in the bladder is high for low-intensity infections. This is consistent with the conclusion of Smith, Elwi, Kamel and Lichtenberg (1975), based on egg/gram data, that such infections may be initiated in the bladder. The correspondingly high proportion of eggs in the ureters with high-intensity infections indicates that increased intensity may have a disproportionately large pathologic effect on the infected individual.


Application of the four-parameter logistic model to bioassay: comparison with slope ratio and parallel line models. Bioassays with a quantitative response showing a sigmoid log-dose relationship can be analysed by fitting a non-linear dose-response model directly to the data. It is demonstrated that the four-parameter logistic model, previously applied to immunoassay (Healy 1972), is applicable to the free fat cell bioassay of insulin (Moody, Stan, Stan and Gliemann 1974). It is shown that the standard slope ratio and parallel line models for bioassay can be considered as approximations to the logistic in the extreme dose regions, while the parallel line model can be expected to fit in the middle region. The full statistical analysis of the four-parameter logistic model applied to a general assay design is described. An APL computer program has been developed to facilitate the calculations, which include non-linear curve-fitting, tests of goodness of fit and parallelity, as well as point and interval estimates of the relative potency. Examples of free fat cell bioassays of insulin that have been analysed according to these methods are given. Efficient estimation of the potency calls for concentrating the doses in the region with the steepest slope of the dose-response curve. With respect to testing the parallelity and to allow for assay-to-assay variability and unpredictable potencies, it may be preferable to use an assay design with doses distributed over a wide range and to apply a dose-response model which, like the four-parameter logistic, is capable of fitting over the whole feasible dose range.


A likelihood ratio statistic for testing goodness of fit with randomly censored data. A likelihood ratio statistic is proposed for testing goodness of fit with grouped data which are subject to random right censoring. It is shown that, under appropriate conditions, this statistic has an asymptotic chi-square distribution which is non-central under contiguous alternatives. A formula is given for the non-centrality parameter. Two examples are given. The first concerns data from a large scale animal survival study with serial sacrifice where it is attempted to fit the Weibull, Gompertz and exponential power distributions to life length. The second example concerns marijuana usage and this needs an extension of the test to the doubly censored case. Another use of the statistic is to provide a quantitative method of ranking the fit of various proposed models to survival or reliability data.


Compartment model approach to the estimation of tumor incidence and growth: investigation of a model of cancer latency. Consideration is made of the problems involved in determining the effects of a chronic disease process, such as stomach cancer, on the observed mortality of the U.S. population. Specifically, since the time of initiation of tumor growth is unknown and the tumor becomes clinically manifest only after reaching considerable size, the early rate and pattern of tumor growth is unobserved. As a possible solution to the analysis of such problems, it is proposed to use stochastic compartment modelling techniques which deal with the problems of estimating the transition probabilities of a partially observed stochastic process. Implementation of the stochastic compartment techniques in this case depends on the selection of certain mathematical expressions from theories of carcinogenesis, epidemiologic studies and animal studies which allow the calculation of transition probabilities to unobserved states by making them explicit functions of time or age. Though the selection of the specific functions might be subject to debate, the general strategy of explicitly selecting such functions, and thereby exposing them for review in terms of biologic reasonableness and consistency with the data, seems to be a valid and useful methodology. Furthermore, various ways of viewing the model results (say from its internal behavior, e.g., from implied distributions of waiting times in various disease states) yield different insights into the various factors in carcinogenesis. The model, with parameters representing tumor incidence, time to tumor death given onset, genetic susceptibility to tumor growth and the effects of competing forces of mortality, is fitted to data on deaths due to stomach cancer for male U.S. residents age 25 and over in 1969. Two basic forms of the model, one with a waiting time distribution for occupants of the latent state and another with a single latency time, achieved excellent fits to the data. Examination of parameter estimates and compartment waiting time distributions are consistent with theoretical expectations and intuition. It is concluded that such strategies, involving the integration of clinical, experimental and vital statistics data into a comprehensive model of population carcinogenesis, are potentially powerful tools for investigation of the temporal dimensions of disease development in a human population.


A method for plotting the optimum positions of an array of cortical electrical phosphenes. The cortical visual prosthesis provides one approach to the substitution of vision in blind people. Usable visual information is provided in the form of phosphenes, and in order to make use of the prosthesis the positions of the phosphenes in visual space must first be determined. Such phosphene maps have to be constructed from observations of the angle and distance between various pairs of phosphenes. Because of the variation in repeated observations of the same phosphene pair, some method is needed to provide the 'best' fitting map to the observations. By formulating the problem as one involving the minimization of a function of many variables, an algorithm is constructed which determines a two-dimensional co-ordinate for each phosphene by minimizing one of two criteria indicating the fit of the map to the observations. The minimization algorithm employed is, essentially, a 'steepest descent' procedure, and initial co-ordinate values are provided by a triangulation method.


Ascertainment models for human families selected through several affected children. Sampling models for families having normal and affected children and being selected through information about two or more of the affected ones have been developed. Such a model, a so-called ascertainment model, yields the conditional probability that a family has r affected children given that it has s children altogether and that it has been selected or ascertained with a probability which is proportional to a given power of the number of different groups of m less than or equal to r affected children. When the power equals zero or one the model is simplified considerably. If also m = 1 we get the well-known complete ascertainment and single ascertainment model as special cases.


Circular triads when not all paired comparisons are made. In paired comparison experiments, especially those involving sensory perception, it is sometimes impossible or undesirable to perform all possible comparisons. As when all comparisons are made, the number of circular triads can be used as a measure of inconsistency in the responses of a particular judge. A computational method for determining the number of circular triads is presented in this paper.


Defective microbicidal function of neutrophils in haematological malignancies and lymphomas: correction by levamisole in vitro. The ability of neutrophils to kill Candida guilliermondii was investigated in patients with various haematological malignancies and lymphomas. Twelve of 24 patients showed significant depression of Candida killing in vitro in comparison with normal controls. The addition of levamisole to the test system, in a concentration of 1 X 10(-7)M, resulted in the correction of the Candida killing defect in 7 of 8 patients.


Daunorubicin, daunorubicinol and DNA plasma kinetics after I.V. administration of daunorubican-DNA complex in the rabbit. The pharmacokinetics of daunorubicin and daunorubin-DNA complex were studied in the rabbit after i.v. bolus injection and a 4hr infusion period. The plasma levels of daunorubicin and daunorubicinol were measured by high-pressure liquid chromatography and the DNA plasma levels by means of 125I labelled DNA. The results demonstrated a slower distribution of the complex; however, the more rapid decrease in the plasma levels of daunorubicin than that of DNA suggested that this complex essentially constitutes a "daunorubicin circulating pool" from which the drug diffuses more slowly than after the administration of uncomplexed daunorubicin.


Effect of thioglycollate on macrophage lysosomal enzymes. Mice peritoneal macrophages obtained after i.p. injection of a medium containing thioglycollate (Institut Pasteur, Paris) have increased levels of beta glucuronidase and acid phosphatase, when compared with macrophages obtained without previous thioglycollate injection. The maximum increase is observed between 7 and 10 days after injection and reaches up to 3 to 4 times the normal activity. When using separately the various components of the medium, the same phenomenon may be observed but never to the same degree. The injection of thioglycollate also produces: a) an increase in total number of peritoneal cells, and b) an increase in the percentage of macrophages among these cells. Kinetic studies suggest that thioglycollate injection first induces an increase in the number of peritoneal macrophages and subsequently macrophage modifications resulting in lysosomal enzyme increase.


Absence of any detectable activity of the membrane marker enzyme 5'-nucleotidase in human red blood cells. We have investigated in human red blood cell membranes the presence of a 5'-nucleotidase, which is considered a general marker of plasma membranes. No activity was detectable with a highly sensitive colorimetric method. This absence is not due to the rapid decline of enzyme activity in the course of red cell ageing, nor to its release during membrane preparation; nor is it due to substrate accessibility hindrance to the active center of the enzyme. Thus, the ubiquitousness of 5'-nucleotidase in plasma membranes is questioned.


Inhibition of CFU-S entry into cell cycle after irradiation and drug treatment. The cell cycle inhibition of pluripotent bone marrow stem cells (CFU-S) by a fetal calf bone marrow extract (BME) was studied. The normally quiescent cells were made to enter cell cycle by treatment with either irradiation or the phase specific drug cytosine arabinoside (Ara-C). Using the vitro-vivo system of Frindel et al., we have shown that when the BME was added to the incubation medium, no triggering of CFU-S into cycle could be observed. The inhibitory effect was also demonstrated when the BME was injected simultaneously with the drug. The possible relationships of BME with stimulating factors controlling CFU-S entry into cycle are discussed.


Distribution of nuclear pores and perinuclear dense substances in spermatocytes I of some Oedionychina fleabeetles. The nuclear envelope of growing postpachytene spermatocyte I differs notably in structure between the fleabeetles Omophoita cyanipennis and Oedionychus bicolor. The former species shows a more conventional structure with an even and probably random distribution of nuclear pores, and a strongly electron-opaque layer of fibrogranular material (FM) separated from the outer nuclear membrane by an intermediate layer of about 40 nm thickness. Peripherally from the FM layer, a continuous corona of granular dense material (GM) is accumulated around the nucleus. In Oedionychus, all nuclear pores are clustered in "nuclear sieves", i.e., shallow, cup-like indentations of the nuclear envelope. The sieves are filled with an electron-opaque substance resembling the FM of the Omophoita spermatocytes. This substance is kept at a distance of about 40 nm from the outer nuclear membrane. GM is produced only at the sives, and is thus discontinuous. The sieves with their contents are called nuclear sieve complexes (NSC).


The mechanism of action and interaction of regulators of cell replication. The oscillator concept of the cell cycle suggests that regulation of replication is achieved through a switch-like process. This is triggered when the values of parameters governing the behaviour of an intracellular control system exceed thresholds (bifurcations) which separate oscillatory and non-oscillatory (or damped oscillatory) modes of operation. On this basis it becomes possible to explain (a) how a given regulator can have diverse effects, (b) how distinct agents can have similar responses and (c) how various agents interact when controlling replication. The relevance of the malignant transformation is also briefly discussed.


The relationship between the transition probability and oscillator concepts of the cell cycle and the nature of the commitment to replication. The oscillator concept of the cell cycle predicts the existence of threshold conditions within the cell which must be exceeded before replication is initiated. It is shown (a) that if the conditions are subthreshold, random disturbances can trigger a cycle of the oscillation (round of replication) and (b) that the probability of this occurring increases as the state of the system approaches the threshold. It is concluded that the oscillator concept explains the data on which the transition probability model is based. It also accounts for the ability of cells to replicate even when the mitogen is present for a limited period only.


Feedback quenching as a means of effectively increasing the period of biochemical and biological oscillators. A cellular oscillator can be expected to modify the levels of other constituents. In turn, some of these are likely to modulate the behaviour of the oscillating system. Under appropriate conditions this feedback can temporarily quench the periodicity. By such means the frequency of the oscillation can be effectively reduced by a factor of ten or more.


Formation of amino acids from aliphatic nitriles and aliphatic amines by contact glow discharge electrolysis. Contact glow discharge electrolyses (CGDE) were carried out relative to the prebiotic formation of amino acids by amination of aliphatic nitrile in aqueous ammoniacal solution, and by cyanization of aliphatic amine by sodium cyanide. The CGDE of propionitrile by amination followed by hydrolysis resulted in the formation of glycine, alanine and beta-alanine. The reaction of ethylamine by cyanization, gave glycine, alanine, beta-alanine, aspartic acid, and serine. In these reactions, a relatively high ratio of glycine was observed. This could be explained by the cleavage of the alpha,beta-carbon bond, which was broken easily, due to the strong electron-attracting property of the nitrile group of propionitrile and the resulting alpha-aminopropionitrile.


The relationship of CO2 assimilation pathways and photorespiration to the physiological quantum requirement of green plant photosynthesis. The quantum requirement of green cells for CO2 fixation has been evaluated and discussed in view of the recent discovery of photorespiration and of multiple biochemical pathways for photosynthetic CO2 fixation. The reported quantum requirement of algae generally is near 9 quanta per CO2 fixed. It is suggested that the high CO2 concentrations and low O2 concentrations used for these algae experiments would have completely suppressed photorespiration and, therefore, the minimum number of quanta required to fix 1 CO2 molecule was correctly determined in these experiments. With higher plant leaves, when measurements are made under physiological environments, quantum requirements range from about 12 to 20 quanta per CO2 fixed. It is suggested that these physiological quantum requirements are higher because photorespiration is functional in these leaves and that photorespiration requires energy. The energy requirement of photorespiration was derived using biochemical models of leaf photosynthesis combining photorespiration with specific biochemical pathways for CO2 fixation. The calculated physiological quantum requirements for C3, C4 and CAM plant photosynthesis are 13, 15 and 17 respectively. The literature values on quantum requirements correspond well with these biochemical models of net photosynthesis. However, it was concluded that the biochemical models fail to give a complete description of photosynthesis in plants using the C4-dicarboxylic acid cycle.


[Experimental reproduction of a secondary pacemaker center for alimentary motivation]. In chronic experiments on rabbits the possibility of artificial modeling of motivational feeding pacemaker's function by different limbic-reticular structures was investigated. It was shown that simultaneous stimulation of the lateral hypothalamic "feeding" centre with various structures of the limbic-reticular complex makes secondary pacemaker of feeding motivation in the midbrain reticular formation only.


[Confirmation of the hypothesis concerning the existence of a diffusion barrier in the region of the nodes of Ranvier of myelinated nerve fibers]. It was shown that during rhythmic stimulation of the node of Ranvier in the potassium-free solution there was an exponential decline of the trace hyperpolarization. This is attributed to the fact that potassium ions released from the fiber during the activity collect in the premembranous space separated from the external solution by diffuse barrier.


[Rhombencephalon and vasomotor reflexes to impulses of somatic A-fibers]. Cats decerebrated so that the medulla oblongata remained connected with a greater or lesser part of the pons Varolli were immobilized with flaxedyl or succinylcholine; arterial pressure (AP) responses to impulses (at the frequency of 10 s-1) of different subgroups of the tibial nerve A-afferents were studied. Impulses of the Abeta + Adelta1-afferents and of the most excitable part of Adelta2-afferents lowered AP in all the animals. Addition of all the Adelta2-afferent impulses enhanced this AP fall in 79% of the cats and only 21% of them did it evoke a rise of AP. Inclusion of Adelta2-fiber impulses into the afferent inflow either did not alter the average AP decrease or evoked a weak, and only sometimes, a more pronounced AP rise. It was found crucial to keep intact the structures of the ponto-medullary junction, as well as the most rostral part of the medulla for sharp decrease of the pressor reflexes or for the appearance of the depressor ones, instead. Consequently, in this part of the hind brain there are structures exerting a tonic depressive influence on the exciting effect of the somatic A-afferent impulses on the vasoconstrictor neurons, thus unmasking the existence of the inhibitory component of their action on these neurons. In unanesthetized cats this action of the hind brain structures is tonically inhibited by the midbrain.


[Effect of subdiaphragmatic vagotomy on sodium and potassium distribution in the bodies of rats]. The state of sodium and potassium metabolism in the organism of male rats was studied by the organic distribution of these elements 1, 7, 14, and 19 days after bilateral subphrenic vagotomy. This operation proved to lead to disturbances of electrolyte metabolism, most pronounced 1 and 7 days after the operation. Relative normalization of sodium and potassium content was noted in 14 and 19 days.


[Effect of several hormones on the intensity of experimental free-radical lipid oxidation reactions]. The effect of adrenaline and hydrocortisone on the processes of free radical oxidation of lipids in rabbit erythrocytes was studied in experiment in vivo against the background of altered lipid metabolism. Adrenaline in a dose of 0.1 mg/kg and hydrocortisone in a dose of 5 mg/kg induced an increase in the amount of hydroperoxidase of fatty acids recorded by the changes of the UV spectrum. The data obtained served in confirmation of the fact that adrenaline and hydrocortisone possessed prooxidant properties, apparently mediated, this being connected with their fat mobilizing effects.


[Phospholipid metabolism in the microsomes and cytosol of the brain tissue of normal rats and rats with hypoxic hypoxia]. The content and the intensity of metabolism of various phospholipid groups (phosphatidylcholines, monophosphoinositides, aminophospholipids) was studied in the homogenate, microsomes, and cytozol of the rat brain under normal conditions and in hypoxic hypoxia (240 mm Hg). Phospholipid content per 1 mg of protein was the highest in the microsomes, and the least in the cytozol. However, the total phospholipids of the cytozol had the greatest rate of metabolism of their phosphate groups. Without influencing the phospholipid content, hypoxia depressed the intensity of their metabolism, and this depression proved to be approximately the same in all the tissue preparations under study.


[Effect of an industrial frequency alternating magnetic field on the functional state of the thyroid gland and thyroxine absorption by the organs of rats]. A study was made of the 131I radioisotope absorption by the thyroid gland, thyroxin binding by a number of tissues, and also protein-bound iodine (PBI) content in the blood plasma of albino rats after the application of alternating magnetic field (AMF)--industrial frequency 200 Ersted voltage--of various duration and periodicity. Plasma PBI increased in response to the 15-minute AMF application. When the exposure was increased to 6.5 hours and especially to 24 hours there was a reduction of the PBI level and of the process of 131I-thyroxin binding by the tissues of the testes, heart, liver, and spleen. The AMF application for 6.5 hours a day for 5 days resulted in a significant elevation of 131I in the thyroid gland and of the PBI, but the 131I-thyroxin binding by the tissues decreased markedly. It is suggested that functional condition of the thyroid gland and the tissue reaction to thyroxin altered depending on the AMF duration and periodicity of action.


[Prevention of the myocardial damaging effect of isadrin by curantil]. As revealed, in experiment on albino pubertal rats single subcutaneous injection of isadrine caused electrocardiographic and ultrastructural alterations characteristic of ischemia and necrosis of the myocardium, as well as of its contractile capacity disturbance. Preliminary three-day administration of curantil in a dose of 10 mg per kg body wt produced a marked protective effect on the isadrin damaged myocardium of pubertal rats.


[Nature of the humoral factor from bone marrow stimulating antibody production]. An active factor doubling the antibody synthesis in the culture of immune lymph node cells was isolated from the supernatant of the cultures of bone marrow cells from intact donors. Gel chromatography was used for this purpose. The stimulant of antibody producers (SAP) was eluated at the site of cytochrome C exit; the factor is heat-stable and has the mol wt of 1300 daltons. SAP production needs RNA and protein synthesis, but does not require DNA synthesis. The radioactive label showed that SAP includes ribonucleotides and amino acids. It is suggested that SAP plays an important role in the regulation of antibody synthesis.


[Changes in the resistance of different strains of mice to tumor development in the presence of immunologic responses]. The experiments on adult mice of varions breed lines have shown that direction of change of the resistance to cancer under conditions of the same immunological influence can be determined by genetic properties of an organism. The author believes that it is worthy of attention that anticancer resistance decreases only in that lines of mice in which was observed some predisposition to appearing of condition of allergy to tuberculine, as it was shown in experiments using the full adjuvant of Freund.


[Lower urethane carcinogenicity for the lungs of thymus-free nude mice in comparison with immunologically normal littermate mice]. Lung adenomas arose in 2 of 10 nude mice injected twice with urethane in a dose of 1 mg/g of body weight; these tumours were revealed in 7 of 10 immunologically normal littermates treated in the same way. Mean adenoma numbers were 0.2 +/- 0.13 per nude mouse and 1.2 +/- 0.36 per normal mouse (P less than 0.05). The data obtained do not agree with the immunological surveillance concept which predicts greated number of tumours in the nude mice in comparison with the normal ones.


[Geometric complementarity of the primary structures of histone molecules H2A, H2B, H3, H4 and several possible consequences of this phenomenon]. The paper treats of the correlations between the position geometry of the extended successions of the residue of basic amino acids and those nonbearing any positive charge along the polypeptide chains of the histone H2A, H2B, H3, H4 molecules forming nucleosomes protein frame. The number of histone packing variants in the tetramere conforming to the conditions of the revealed complementarity reached the value of 10(4), and in respect to histone octamere--10(8). A hypothesis was put forward on structural heterogeneity of nucleosomes (of functional significance) the choice of whose protein frame packing variant could be realized by the mechanisms of allosteric regulation of the primary structure of DNA molecule section serving as the nucleosome element.


[Effect of the thymus on the ability of hematopoietic stem cells to recover from sublethal radiation injuries]. Following fractional irradiation of the mouse bone marrow (300 rad in vitro + 300 rad in vivo) the damage of stem hemopoietic cells was more pronounced when the interval between the irradiations was 30 min as compared to five hrs, on account of recovery from sublethal radiation injury (Elkind's repair of radiation damages). In adult thymectomized mice the capability of stem hemopoietic cells to Elkind's repair was sharply deranged 2.5 to 5 months after the operation. This effect of thymectomy was abrogated by the newborn thymus graft.


[Changes in the amount of protein in hypothalamic neurons of sexually mature rats castrated neonatally]. A change in the amount of protein in the neurons of the anterior and mediobasal hypothalamus of sexually mature male rats castrated neonatally was observed in the study using the interferometric method. A considerable increase was recorded in the dry weight of the neurons in the medial preoptic region and the arcuate and ventromedial nuclei of the hypothalamus. The most pronounced changes were observed in the nuclei of these neurons. The results obtained point to the influence of androgens on the hypothalamic structures responsible for the regulation of both cyclic and tonic release of gonadotropic hormones in sexually mature animals during sex differentiation of the brain.


[Submicroscopic changes in the thyroid gland in burns]. Submicroscopic changes of thyrocytes and perifollicular capillarites were studied in pubertal guinea pig males on the 1st, 2nd, 7th, 14th, 21st, and 28th days of burn disease. During the burn shock macrofollicles formed by flattened thyrocytes dominated in the thyroid gland. The capillaries were characterized by the lumen dilatation and disturbance of the wall ultrastructure. The cells increased in height, and there was hypertrophy and hyperplasia of the intracellular organellae on the 7th and the 14th days. Along with hyperplastic processes in thyrocytes and endothelial cells destruction of the membrane cell components developed which caused deep necroblas cell injury and severe disturbances of the vascular parenchymatous relationships in the organ at later periods of the disease (the 21st and 28th days).


[Determination of "settling factor" (f) by the hematopoietic stem cell cloning test in mouse spleen and bone marrow]. The effect of distribution of injected colony-forming units (CFU) in the recipient's organism was studied. The distribution was assessed by the "sedimentation factor" (f) criterion. This factor was found by the number of colonies revealed on histological sections of the spleen and femoral bone marrow in comparison with the number of colonies visible on the surface of the spleen. Macroscopic count of the colonies on the spleen permits, to assess the f value both in the whole spleen volume and in the femoral bone marrow. In this case f value was independent of the character of CFU differentiation. f value could change depending on the physiological condition of CFU population. In irradiation of the bone marrow CFU in a dose of 200, 400 and 600 R f value in the spleen decreased in comparison with control, but remained unchanged in the bone marrow.


[Functional morphology of accessory neurosecretory cells in cat hypothalamus]. In acute experiments on tomcats after stimulation of supraoptic nuclei (SON), postoptic nuclei (PON), preoptic area of the hypothalamus, cervical sympathetic nerve (SCN) and vagal afferent fibers (VA) the following data were obtained in the preparations stained by Gomori method: four pair accessory cell groups in the rostral part of the hypothalamus were observed: 1) periventricular group (along the walls of the III ventricle; 2) the preoptic group (above the preoptic recess; 3) the parafornical group (around the fornix columns), and 4) the spindle-shaped group. The latter group was revealed constantly both in control and in the stimulated animals in all the experiments. In direct stimulation of the SON and PON and also if the CSN and the vagus direction of its reaction coincided with such in the SON and PON, whereas in stimulation of the VA of the hypothalamus the synthesis activation was observed against the background of unchanged (in comparison with control) state of the neurosecretory nuclei.


[Histotopography of several metabolic processes in the heart]. Localization of basic metabolic processes was investigated by histochemical methods in the heart of untrained, trained, and overtrained rats in relative rest state, and at the stage of single and repeated physical loads in case of urtrained rats. In the untrained rat heart myocardium the glycogenolysis and glycolysis processes were more active in the subendocardial layers, and those of fatty acids and ketone bodies oxidation--in the subepicardial layers. Reverse relationships were discovered in the trained and overtrained rats myocardium. The subpericardial layers role for supporting the heart function in sharp activation of its work was demonstrated.


[Changes in ultrastructural synaptoarchitectonics induced by endotoxin]. The authors studied the ultrastructure of synapses of the dog sensory-motor cortex in response to intravenous injection of typhoid endotoxin. The most pronounced shifts were noted in the dendrite neuron apparatus. Activation in the cortical structures was connected with an increase in the number of functioning synapses and reconstruction of interneuronal connections. There was an increase in the length of the contacting membranes, and of the quantity of synaptic vesicles; the content of dense core vesicles is released. Depression is associated with dystrophic changes in the synapses.


[Ultrastructural features of the kidney following administration of antidiuretic hormone]. In the course of antidiuresis induced in rats by the antidiuretic hormone injection on the background of moderate water load (in difference from the hormone injection without the water load) the expansion of the extracellular spaces and of the basal labyrinth in the epithelium of the collecting tubules and of the thin descending limb of Henle's loop was revealed; this was apparently associated with the presence of intratubular pressure gradient under the given conditions. In both the experimental versions there occurred cytoplasmic vacuolization and expansion of the interstitial cells perinuclear space in the kidney medulla. These data confirm the hypothesis on the role of the intercellular contact in the transepithelium water reabsorption path in the kidney during the urine concentration process, and indicate the participation of the interstitial cells in this process.


[Study of the constituent proteins of brain structures by the technic of electrophoresis in a continuous polyacrylamide gel gradient in capillaries]. The author compared the protein composition of the brain structures (premotor zone of the cortex, CA3 are of the hyppocampus, the caudate nucleus, the frontal lobe of the cerebellum) in rats by electrophoresis in the continuous gradient of polyacrylamide gel pores in capillaries. The method used proved to possess a much greater resolving capacity in comparison with electrophoresis in the homogeneous gel concentration; no differences could be revealed in the protein composition of the brain structures under study.


[Method of quantitative determination of natriuretic factor in biological fluids]. The natriuretic factor was determined quantitatively on the isolated rat jejunum segmens turned inside out. After addition of the test blood plasma into the incubation medium the changes in fluid absorption by the intestinal epithelium were recorded. The amount of the natriuretic factor capable of complete blocking the transport activity of the intestinal epithelium was accepted as 1 intestinal unit of the natriuretic factor.


[Double labeling method for electron microscopic autoradiography]. A method for investigation of the synthesis of two different substances of the RNA and protein in the same cell was described. Two specific tritium-labeled precursors--uridine and proline were administered to the animals. The difference in the RNA and protein labeling was based on the fact that biosynthesis of these macromolecules was localized in different cell parts. Comparison of the results obtained and those of the two control experiments in which one of the precursors was administered has shown the fitness of the present method for simultaneous investigation of the RNA and protein synthesis in the wound fibroblasts.


[Method of studying the functional state of pulmonary alveolar macrophages during exposure to atmospheric pollutants]. On the basis of experimental research results a method to assess the functional state of pulmonary alveolar macrophages in rabbits and rats has been proposed as a criterion of the biological effect of chemical atmospheric pollutants. The test involves a cytological assay, determination of the viable cells quantity and of the phagocytic competence, and also the biochemical study of alveolar macrophages enzymes activity (acid phosphatase, beta-glucuronidase, lysozyme, beta-galactosidase, beta-glucosidase, N-acetyl-beta-D-glucosaminidase). It has been shown that this method is informative and reliably reproducible, and that it was reasonable to use it in environmental health and other branches of experimental biology and medicine.


Augmentation of fetal hemoglobin (HbF) synthesis in culture by human erythropoietic precursors in the marrow and peripheral blood: studies in sickle cell anemia and nonhemoglobinopathic adults. We cultured marrow and peripheral blood erythropoietic precrusors in methylcellulose clonal assay and measured the synthetic rates of HbA, A2, F, and S in patients with and without sickle cell anemia. Hb was labeled with 14C-amino acid in culture, separated by slab gel isoelectric focusing techniques, and quantitated by autoradiographic methods. Comparison of marrow late (CFU-E) and early (BFU-E) precursors from patients without hemoglobinopathies showed that preferential synthesis of HbF is limited to early precursors. Simultaneous examinations of Hb synthesis by blood and marrow early erythropoietic precursors confirmed the similarity of the biosynthetic capabilities of the precursors from the two sources. Increasing concentrations of erythropoietin (Ep) in culture corresponded with increases in the percentages of HbF synthesized by blood BFU-E of normal individuals. HbF biosynthesis by blood BFU-E from sickle cell anemia patients was significantly higher than that synthesized by nonanemic individuals and showed significant individual variations. HbF synthesis in patients with sickle cell anemia was partially dependent on Ep concentrations in culture. Cell culture of circulating erythropoietic precursors in man appears to provide a unique tool for studying the control mechanisms of Hb synthesis in man.


Hematologic changes during spleen colony development in nonirradiated mice. The mechanism of spleen colony formation in nonirradiated mice was investigated. When the spleen cells of C57BL mice immunized against CBA-T6T6 mice were injected into the nonirradiated BT6F1 (C57BL X CBA-T6T6) hybrid mice, the number of hematopoietic stem cells (CFU-S of C57BL mouse origin that settled in the spleen of the BT6F1 mice continued to decrease in the first 9 days and then started to increase, with a doubling time of about 36 hr. Colonies were detected on the surface of the spleen 16-22 days after the cell injection. The slower appearance of spleen colonies in nonirradiated mice (compared with 6-10 days in the irridiated animals) appears to be due to retarded start of differentiation and to the prolonged doubling time of CFU-S in non-irradiated mice.


Variability of the homeostatic response to altered p50. Blood from carriers of hemoglobin Osler (Hb Osler) had almost the same oxygen affinity as that of carriers of Hb McKees Rocks (Hb MR) (P50 10-11 mm Hg), but Hb concentrations were higher in male carriers of the former (21.6 versus 17.2 g/dl). Two carriers of each Hb were studied to compare their adaptations to altered oxygen affinity and their responses to phlebotomy. All four were healthy, and all excreted normal amounts of erythropoietin. Carriers of Hb MR had somewhat lower mixed venous pO2 than carriers of Hb Osler. There was no suggestion that phlebotomy impaired ability to exercise in either group of patients.


Canine cyclic hematopoiesis: effects of chronic endotoxin administration. Endotoxin was given to grey collie dogs to investigate the mechanism of cyclic hematopoiesis. Over prolonged periods of daily administration, low doses of endotoxin (0.1 microgram/kg/day) failed to change the cycling of blood neutrophils or reticulocytes. However, higher doses of endotoxin maintained at a plateau level (5 microgram/kg/day) eliminated the cyclic changes in neutrophils and stabilized the reticulocyte and platelet counts in the normal range. Administration of endotoxin at this dose also eliminated the cyclic marrow differential count fluctuations characteristic of this disease. We infer from these results that endotoxin ameliorates the cyclical changes in blood cell counts by regulating hematopoietic proliferative activity at the stem cell level.


Measurement of sickling by controlled temperature increase. Previous experiments to study the rate of red cell sickling have employed rapid mixing apparatus for SS cells with dithionite and have shown that the half-time of sickling is quite rapid, on the order of seconds. An alternative approach is to slow down the rate by taking advantage of the negative temperature coefficient of the process. We developed a method in which deoxygenation of a cell suspension is carried out at 0 degrees C. A linear temperature gradient to 37 degrees C is applied, and a gradual increase in the percentage of sickled cells is observed. At a heating rate of 1.5 degrees C/min the temperature at which half of the cells became sickled was 19 degrees C for SS cells treated with dithionite, 22 degrees C for SC cells, 28 degrees C for AS cells, 22 degrees C for cyanate-treated SS cells, and 23 degrees C for SS cells in the presence of 0.1 M butylurea. Thus this method promises to be useful for the study of sickling rates and the screening of potential anti-sickling agents.


Erythroid regulatory factors: correlation of detectable titers in vivo and in vitro. Titers of erythroid regulatory factors (ERF), as measured in vivo with a standard erythrocythemic mouse technique, showed a highly significant correlation with those obtained in vitro with a fetal mouse liver cell (FMLC) assay. The results from the assay in vitro were somewhat higher than would be predicted from the assay in vivo. Nevertheless, the FMLC technique has been found to be a valid and useful technique particularly in the study of serum ERF titers.


Granuloerythropoietic colonies in human bone marrow, peripheral blood, and cord blood. Colonies that contain granulopoietic and erythropoietic cells can be grown in specimens of human bone marrow, peripheral blood, and cord blood. Growth of these colonies is promoted by media conditioned by leukocytes in the presence of phytohemagglutinin (PHA-LCM) and the addition of erythropoietin on days 4 or 5 to the cultures. Sedimentation velocity profiles for these granuloerythrocytic colonies suggest their origin from single cells (CFU-G/E) rather than from doublets or clumps. This hypothesis is supported by cocultivation of male and female specimens. Cells in granuloerythrocytic colonies that developed in such mixing experiments were either uniformly female by Y-chromatin analysis or contained Y-chromatin bodies in both the granulocytic and erythroid cells.


Influence of environmental factors excluding ultra violet radiation on the incidence of skin cancer. Cancers of the skin are not properly registered and our lack of precise knowledge of the influence of environmental factors is due both to a failure to report and a failure to attribute because many tumours are not recognised as due to environmental factors and escape notification due to lack of knowledge and teaching. The long latent period also interferes. The commonest cancer is squamous cell carcinoma followed by basal cell carcinoma. Melanoma is exceedingly rarely environmental. The main causative agents are: Polycyclic aromatic hydrocarbons (PAH), inorganic arsenic and ionising radiation. PAH induce 4 times more cancer of the scrotum in workers using cutting oils or pitch than expected. These subjects have also increased incidence of second primaries of both the skin and internal organs. The latent period varies from 20 years (exposure to coal tar) to 50 years or more (exposure to mineral oils). Exposure to pitch may result in 11 fold increase incidence of squamous cell carcinoma. Skin cancer due to arsenic is rare. It has been seen in sheep dip workers, in patients treated with Fowler's solution and in vineyard workers using arsenical pesticides and drinking contaminated wine. The latent period may go up to 60 years. Ionising radiation over 1,000 rems may cause basal and squamous cell carcinoma. The latent period varies from 7 weeks to 56 years (average 25--30 yrs).


Biochemical aspects of chemical carcinogenesis. This article briefly outlines three major biochemical problems in relation to the presence of chemical carcinogens in mammalian cells: (a) the enzymatic systems responsible for the chemical carcinogen metabolism; (b) the nature of the reactive metabolites and (c) the cellular target(s). References and examples are only given for the field of the polycyclic aromatic hydrocarbons.


Mutagenicity and carcinogenicity of 8-MOP/UVA in cell cultures. HGPRT-deficient mutants of chinese hamster cells and human skin fibroblasts are selected with 6-thioguanine after treatment with the combination 8-MOP and UVA. Calculation based on this study indicate that 1.7 X 10(-5) mutants will be induced in the epidermis per session of PUVA therapy. Induction of cell-transformation was observed in C3H and 3T3 mouse cells.


Formation of thymine containing dimers in skin exposed to ultraviolet radiation. Nuclear DNA appears to be the major molecular target for the inhibitory, mutagenic and lethal effects of ultraviolet radiation on cells in culture. Cyclobutyl dimers between adjacent pyrimidine bases, the major photochemical lesions for these effects in prokaryotes, also play a part in UVR effects on eukaryote cells. Pyrimidine dimers have been isolated from in vivo UV-irradiated guinea pig and mouse skin. The wavelength dependence for dimer induction is similar to that for acute skin reactions but no direct causal relationship has been established. Sunlight UVA may induce dimers in skin DNA. Excision of dimers from mouse skin in vivo is deficient as it is for most rodent cells in culture; human cell excision is efficient and the difficulties in interpretation of UV-carcinogenesis results with mice in terms of human skin cancer are therefore, increased.


Xeroderma pigmentosum: heterogeneous syndrome and model for UV carcinogenesis. Xeroderma pigmentosum (XP) is a rare inherited, heterogeneous syndrome with pigment anomalies, sun sensitivity, multiple cutaneous neoplasms and abnormal self protecting systems (SPS). The transmittence is autosomal-recessive. 50 percent of XP patients gets melanoma and 15 percent have neurological abnormalities. Clinical differentiation, determination of the DNA repair rate and cell fusion studies allow the differentiation of 6 complementation groups including De Sanctis-Cacchione syndrome and the XP variant typ. Pigmented Xerodermoid is a special form. Cytogenetic studies give evidences for the model character of XP for UV carcinogenesis.


Xeroderma pigmentosum and the role of DNA repair in oncogenesis. Biochemical and genetic information on xeroderma pigmentosum (XP) has been briefly reviewed. This indicates that 80 to 90 percent of all XP patients are defective in the excision repair of pyrimidine dimers and are unable to perform the first step of this process as shown, for example, by their inability to undergo the DNA superhelical changes which accompany the initiation of excision repair in normal cells. However, in spite of its apparent biochemical homogeneity, XP is genetically heterogeneous and many genes appear to be responsible for the function of the factor defective in XP. Ten to 20 percent of all XP patients (called XP-variants) are capable of "dimer excision repair" but have difficulties in replicating UV-damaged DNA. The defects of XP and XP-variant affect also the repair of DNA damage caused by a number of chemical mutagens and carcinogens. This has important theoretical and practical implications since it indicates, for example, that the repair systems defective in XP must have broad specificity and that even XP cells not exposed to the harmful effect of light may suffer from poor repair of DNA damage. With regard to cancer, two questions have been considered. Namely, does XP provide a valid general model for UV-carcinogenesis in man and does it show how DNA damage leads to malignant transformation? The first question was answered in the affirmative in view of some clinical but, mainly, of cell biological data indicating that normal and excision defective XP cells differ, more quantitatively than qualitatively, in their response to UV-light. With regard to the second question XP seems to provide some support for various theories on carcinogenesis and, DNA repair defects may favour actinic carcinogenesis in a complex, non-univocous manner. Possibly the most important lesson imparted by XP is that, in man, the stability of the genetic material is dependent on the function of repair systems whose failure may predispose to cancer. In addition, the study of XP has stressed the fact that many genes control DNA metabolism and new evidence is accumulating to show that defects in such genes may contribute significantly to the genetic predisposition to cancer.


Studies on the DNA-excision repair in lymphocytes of patients with recurrent Herpes simplex. Investigations of the semiconservative DNA replication and the excision repair in lymphocytes of patients with recurrent herpes simplex showed defects that could lead to mutations in the DNA with following lower immuncompetence and possibility for activation of already present oncogenic virus formations within the cellular DNA.


Pigmented Xerodermoid: first report of a family. Pigmented Xerodermoid is a variant of Xeroderma pigmentosum characterized by late manifestation of sun--sensitivity, dyschromic and poikilodermatic skin changes and multiple malignant skin tumors in light exposed areas. In contrast to Xeroderma pigmentosum excision repair system is normal, but DNA synthesis after UV--irradiation is markedly prolonged, suggesting that the postreplicational repair mechanism is disturbed. A family of 89 members with 4 siblings suffering from pigmented Xerodermoid was examined. The pedigree of this family suggests autosomal recessive inheritance in this disease.


Quantitative changes in respiratory enzyme activity in premalignant lesions and experimentally irradiated skin. Chronic exposure of human skin to solar irradiation results in a variety of preneoplastic and frankly neoplastic skin lesions. We have shown that in solar keratoses (SK) and in paralesional skin there is instead of an even distribution of succinic dehydrogenase (SDH) activity a relative decreased activity in the granular cell layer. Furthermore, there is enhancement of the usual concentration of glucose-6-phosphate dehydrogenase (G6PDH) activity in the granular zone as well as an increase in total G6PDH epidermal activity. In the experimental part of this study, six normal volunteer subjects had areas of normally non exposed skin (buttocks) irradiated with a 2 Mean erythema dose of ultra violet light (290--400 nm) on between 3 and 5 occasions per week for 2--6 week periods. The results obtained indicated that the same changes in enzyme activity localization take place in artificially irradiated normally non exposed epidermis as seen in normally exposed skin nearby actinic keratoses. It is suggested that these quantitative changes may be the basis of a model for the study of chronic ultra violet light damage to the epidermis.


DNA repair deficiency in lymphocytes from patients with actinic keratosis. DNA repair activity was measured in peripheral blood lymphocytes from 18 patients with Actinic Keratosis and 18 age-matched control subjects, by comparing the incorporation of 3H-thymidine into cells after irradiation with ultraviolet light with that into unirradiated cells. The incorporation was followed autoradiographically or by measuring acid insoluble radioactivity in cells labelled in the presence of hydroxyurea. The repair activity in lymphocytes from Actinic keratosis patients was only 47.1 percent (+/- 6.5%) of that in cells from the control subjects.


Lead concentration in the livers of Canadians. Liver specimens were collected at 114 (83 males and 31 females) autopsies on accident victims and on 4 stillborn infants in seven Canadian Cities. The age of the individuals ranged from newborn to 89 years with about 70% being 19--65 years. The level of lead in the samples was determined by atomic absorption spectroscopy using a carbon rod atomizer. The concentration of lead in liver was low (microgram/g: Mean, 0.37, Median 0.28) at birth and during infancy. In the stillborn infants it ranged from 0.30 to 0.77 (Mean 0.51). 7ale adults had an average level of 1.78 (Median 1.41) whereas in adult females the corresponding values were 0.65 and 0.57. The liver lead concentration peaked at about the end of the fourth decard in adult males. There was no indication of any regional differences.


A kerosen-like taint in the sea mullet Mugil cephalus (Linneaus). II. Some aspects of the deposition and metabolism of hydrocarbons in muscle tissue. The results obtained indicate that the deposition of absorbed hydrocarbons in different segments of the muscle tissue of the sea mullet is proportional to the lipid content of the segment. However the results give no clear indication as to whether the total lipid content of the muscle tissue of individual fish influences the uptake of hydrocarbons from the environment. Evidence has been presented for different rates of metabolism of the n-alkanes as compared to the iso-alkanes and related compounds. Metabolic processes in the sea mullet result in the preferential degradation of the n-alkanes leaving a hydrocarbon mixture in the sea mullet enriched with iso-alkanes and related compounds.


Petroleum hydrocarbon resistance in the marine worm Neanthes arenaceodentata (polychaeta: annelida), induced by chronic exposure to No. 2 fuel oil. 1. Three successive generations of the marine polychaetous annelid Neanthes arenaceodentata taken from a laboratory population, were continuously exposed to one of three sublethal concentrations of No. 2 Fuel Oil water-soluble-fraction (WSFs). During each generation larvae, juvenile, and immature adult polychaetes were challenged with acute (96 hr) doses of No. 2 Fuel Oil or south Louisiana crude oil WSF to test their sensitivity to petroleum hydrocarbons (PHCs). 2. Larvae from all 3 generations, at all exposure concentrations, were no different from control (susceptible) larvae in their sensitivity to the two test oils. F1, F2, and F3 adults exhibited equally increased PHC resistance (X2) compared to control adults. 3. The only evidence of increased resistance beyond that observed in F1 animals was seen in results of bioassays with juvenile worms, wherein PHC resistance increased from slightly below control levels in F1 juveniles to slightly above control tolerance among F3 juveniles. 4. With the exception of F1 worms, removal from chronic exposure 7 or 14 days prior to challenge did not result in termination or reduction of resistance, implicating a genetic mechanism behind PHC resistance in N. arenaceodentata. 5. F3 resistant and unexposed control polychaetes accumulated, metabolized, and excreted a key diaromatic PHC (naphthalene-14C) in quantitatively identical fashion. Mechanisms responsible for resistance appeared unrelated to external permeability and/or excretion rates.


Comparative effects of feeding lead acetate and phospholipid-bound lead on blood and tissue lead concentrations in young and adult rats. Two different forms of lead, lead acetate and phospholipid-bound lead, were fed to young and adult male rats for 10 weeks at the 300 ppm dietary level. Based on the lead concentrations found in selected tissues, our results indicate that the bioavailability of phospholipid-bound lead is similar to that of lead acetate at the 300 ppm level. Young rats had higher concentrations of lead in tissues than did adult rats.


Current concepts of gastrointestinal motility and electrical activity. The motor and electrical events in the gastrointestinal tract correlate far better than do motor activity and transit of intraluminal contents. Two types of electrical phenomenon can be recorded from the smooth muscle of the bowel, namely slow waves and action potentials. Action potentials, which are superimposed on the slow waves, initiate the gastrointestinal contractions and are directly related to changes in intraluminal pressure. The characteristics of the electrical activity in the different parts of the alimentary tract are described, these being dependent on the anatomical recording site, the animal species, and the recording technique. Alterations in motility by neural and hormonal stimuli reflect the changes that these stimuli produce in the gastrointestinal myoelectrical activity.


Rat vas deferens: a specific bioassay for endogenous opioid peptides. The electrically-evoked contractions of the rat vas deferens were selectively inhibited by beta-endorphin, the preparation being much less sensitive to enkephalins and narcotic analgesic drugs. However, introduction of D-Ala in position 2 of [Leu]-enkephalin enhanced the activity of the opioid peptide to the order of that of beta-endorphin. It is concluded that the rat vas deferens preparation constitutes a specific bioassay for endogenous opioid peptides and related compounds.


Potentiation of nerve-induced bladder responses by tetraethylammonium in relation to junctional and extrajunctional muscarinic receptors. 1 The single stimulus responses elicited in the rat urinary bladder were enhanced up to 3 fold by tetraethylammonium chloride (TEA) in the range 2.5 to 10 mM. Responses elicited by repetitive stimulation at 20 Hz were potentiated much less by 2.5 and 5 mM TEA; 10 mM TEA depressed the responses to less than control levels.2 The responses elicited in preparations treated with tetrodotoxin or botulinum toxin during the 20 Hz stimulus trains were one third to one half of control, while single stimulus responses were abolished altogether. After 10 mM TEA the response to the 20 Hz stimulus trains were near control but the single stimulus responses were not restored at all.3 The single stimulus response of control and of TEA-treated bladder preparations were unaffected by atropine (2 x 10(-6) M) but responses elicited by a 20 Hz stimulus train were reduced more than 40% by atropine. After 5 mM TEA the responses to the 20 Hz stimulus trains that had been partially blocked by atropine were immediately restored to near control levels.4 The responses of bladders to carbachol were dose-dependent in the range 10(-6) to 10(-5) M and were atropine-sensitive. After 5 mM TEA the means of the responses produced by graded doses of carbachol were less than control; muscarinic receptors that were blocked by TEA are probably also atropine-sensitive.5 It is suggested that muscarinic receptors in the rat urinary bladder may be divided into: (1) junctional receptors that are resistant to atropine and may be indirectly affected by TEA and (2) extrajunctional receptors that are blocked by atropine and may be directly affected by TEA.


The influence of L-tryptophan and monoamine oxidase inhibitors on catecholamine metabolism in rat brain. 1. L-Tryptophan (100 mg/kg) was administered to rats with or without pretreatment with a monoamine oxidase inhibitor and the concentration of 5-hydroxyindoleacetic acid, homovanillic acid, dihydroxyphenylacetic acid, 3-methoxy 4-hydroxyphenyl glycol, normetanephrine, noradrenaline and dopamine measured in whole brain one hour later. 2. L-Tryptophan increased the concentration of 5-hydroxyindoleacetic acid, homovanillic acid, dihydroxyphenylacetic acid, 3-methoxy 4-hydroxyphenyl glycol and normetanephrine. The concentration of noradrenaline did not change whilst that of dopamine increased significantly. 3. In animals pretreated chronically with a monoamine oxidase inhibitor, tryptophan increased the concentration of dihydroxyphenylacetic acid and homovanillic acid compared to monoamine oxidase alone. 4. The results suggest either a release of dopamine and noradrenaline by 5-hydroxytryptamine, with a compensatory increase in their synthesis, or an increase in the firing of dopaminergic and noradrenergic neurones after L-tryptophan.


Antagonism by clonidine of neuronal depressant responses to adenosine, adenosine-5'-monophosphate and adenosine triphosphate. 1. Adenosine and its nucleotides adenosine-5'-monophosphate (AMP) and adenosine triphosphate (ATP) have been applied by microiontophoresis to neurones in the cerebral cortex of rats anesthetized with urethane. The firing rate of most neurones was depressed, though two cells were encountered which showed biphasic responses to ATP consisting of an initial excitation succeeded by depression. 2. The application of clonidine with iontophoretic currents of less than 25 nA resulted in blockade of the depressant responses to the purines, without affecting responses to noradrenaline, 5-hydroxytryptamine or gamma-aminobutyric acid (GABA). At much higher doses of clonidine, direct depression of cell firing occurred and occasional interaction with noradrenaline was noted. 3. In the case of the biphasic responses to ATP, clonidine seemed to block only the depressant phase. Reduction of the excitatory component paralleled changes of background firing. 4. It is concluded that, in common with some other 2-substituted imidazoline derivatives, clonidine possesses the ability to block responses to purine compounds.


Rock climbing: observations on heart rate and plasma catecholamine concentrations and the influence of oxprenolol. Observations are presented on the electrocardiogram and plasma catecholamine concentrations of 11 healthy men monitored during two rock climbing ascents. A placebo was administered prior to the first climb and an oral dose of the beta blocking agent oxprenolol ("Trasicor") prior to the second. Mean heart rates were 166 (+/- 20.4 SD) and 120 (+/- 10.2) respectively. Median plasma adrenaline concentrations were 0.05 microgram/1 and 0.33 microgram/1 before and after the climbs following the placebo. No significant difference was observed in the adrenaline concentrations before and after climbing following oxprenolol, or of noradrenaline concentrations on either occasion. These results are interpreted as suggesting that this popular sport represents more an anxiety-type of psychological stress than a physical stress and as such is likely to increase moral fibre rather than muscle fibre.