Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biphasic duplex-to-strand transition for the netropsin.poly(dA-dT) complex, phosphate/drug mole ratio (P/D) = 50, has been investigated by high-resolution proton nuclear magnetic resonance (NMR) spectroscopy at the nonexchangeable base and sugar protons in 0.1 M cacodylate solution. The NMR spectral parameters monitor the structure and dynamics of the opening of antibiotic-free base pair regions (55 degrees-65 degrees) and the opening of base regions centered on bound netropsin (90 degrees-100 degrees). The gradual addition of netropsin to poly(dA-dT) results in structural perturbations extending into the antibiotic-free base pair regions that begin to level off above 0.02 antibiotic molecules per polynucleotide phosphate (P/D = 50). The NMR chemical shift parameters at the antibiotic-free base pair regions in the P/D = 50 complex suggest changes in the glycosidic torsion angles of the deoxyadenosine and thymidine residues and less pronounced changes in the base pair overlap geometries. The dissociation rates of the antibiotic-free base pair regions are at least an order of magnitude slower in the P/D = 50 netropsin.poly(dA-dT) complex compared to related parameters for poly(dA-dT) and the P/D = 50 ethidium bromide-poly(dA-dT) complex. There is decreased segmental mobility at the antibiotic-free strand regions in the temperature range (65 degrees-90 degrees) between the two transitions in the biphasic melting curve of the P/D = 50 netropsin-poly(dA-dT) complex. Netropsin stabilizes at least five base pairs, with their center at its binding site.
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PMID:Netropsin-poly(dA-dT) complex in solution: structure and dynamics of antibiotic-free base pair regions and those centered on bound netropsin. 27 45

The binding of tritiated benzo(a)pyrene (BP) to liver DNA of 25 adult male rats (SIV 50) has been determined 50 h after a single intraperitoneal injection of doses between 40 ug/kg and 4 mg/kg. The dose-response relationship is linear up to 1 mg/kg, shows a sigmoid step towards 2 mg/kg and a shallow linear slope above that value. The observed binding ranges from 1.7 to 180 nmoles BP per mole DNA phosphate. The non-linearity between 1 and 2 mg/kg could be explained on the basis of an induction of metabolizing enzymes. A purely mathematical extrapolation of the tumour incidence from a carcinogenic dose (1 x 40 mg/kg for a 20% hepatoma incidence in newborn mice) to human exposure levels (about 0.1 ug/kg per day) would never have followed a step like the one found in our experiments. Our dose-effect study therefore shows how carcinogenicity data could be extrapolated in a biologically founded way to low doses.
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PMID:Extrapolation of carcinogenicity data to low doses with a dose-response study of the binding of benzo(a)pyrene to rat liver DNA. 27 32

The interaction between valproic acid (VPA) and human serum albumin (HSA) was investigated using the equilibrium dialysis technique under various conditions. Solutions of VPA in HSA (2 x 10(-4) M) were dialyzed against isotonic phosphate buffer at 37 degrees C. Protein and buffer compartments were assayed for VPA by GLC. The free fraction (alpha) of VPA increased from 0.13 at 27 microgram/ml to 0.49 at 103 microgram/ml. Scatchard plots were linear, indicating the existence of one type of binding site. The mean (+/- % SD) number of binding sites per macromolecule was 2.06 +/- 3.7% and the mean (+/- % SD) association constant was 2.69 x 10(4) +/- 15.0% liters/mole. The effects of three anticonvulsants (phenytoin, phenobarbital, and carbamazepine) and four major free fatty acids (FFA) (stearic, palmitic, oleic, and linoleic) on alpha were studied. The free fraction, 0.18, was not affected by phenobarbital (20 and 40 microgram/ml), carbamazepine (10 and 20 microgram/ml) or phenytoin (20 and 40 microgram/ml). Each of the four FFA caused a significant increase in alpha: 19--48% increase at 100 microgram/ml of FFA and 88--118% at 200 microgram/ml.
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PMID:Valproic acid binding to human serum albumin and determination of free fraction in the presence of anticonvulsants and free fatty acids. 36 55

By means of titration viscometry a number of distinct modes could be resolved for the interaction between the antibiotic netropsin and DNA species of 50, 58, and 69 mole + (A+T) below r = 0.04 netropsin molecules bound per DNA phosphate group. The number of corresponding binding sites increases with a high power of the (A+T) content. The apparent association constants are very high (greater than 10(6) M-1, some perhaps greater than 10(6) M-1) and also rather different for most of the binding sites. It is suggested that some of these interaction modes differ in the number of hydrogen bonds formed between donors of the ligand and acceptors of the binding sites. The interaction modes were characterized quantitatively by their (species-independent) changes of DNA contour length and by the percentage of local DNA stiffening.
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PMID:Aspects of specific protein-DNA interaction; multi-mode binding of the oligopeptide antibiotic netropsin to (A.T)-rich DNA segments. 39 May

Mentally handicapped children, aged 5--15 years and living in institutions, received fluoride supplement in several sugar products of their diet; in candies, marmalades, jams, fruit juices and in sweet desserts corresponding to 10 mg F as NaF per kg of the sugar (sucrose or glucose) of each product. To two of the four daily candies was also added a NaHCO3 + KH2PO4 mixture (mole ratio 9.8/l, resp.) to substitute for 2.5% of the sugar of the candy. The control children received the respective products without the additives. After stepwise exclusions of subjects for various reasons, e.g. for the absence of permanent teeth, low initial caries activity, strong medication, Down's syndrome, etc., the mean DMFS-increment in the remaining 43 control subjects was 4.5 and in the 41 test subjects 2.6 lesions/100 surfaces at risk, i.e. 42% reduction. Caries arrestment had occurred in these test subjects after the first year, while in the respective controls it was continuously increasing. Among numerous oral and body parameters studied, only surface enamel fluoride in primary teeth was increased by the fluoride supplements and urinary phosphate and calcium excretion decreased.
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PMID:Effect of caries in mentally handicapped children of addition of fluoride and bicarbonate-phosphate to dietary sugar products. 39 99

Intact gas vesicles of Microcyclus aquaticus S1 were isolated by using centrifugally accelerated flotation of vesicles and molecular sieve chromatography. Isolated gas vesicles were cylindrical organelles with biconical ends and measured 250x100nm. The gas vesicle membrane was composed almost entirely of protein; neither lipid nor carbohydrate was detected, although one mole of phosphate per mole of protein was found. Amino acid analysis indicated that the protein contained 54.6% hydrophobic amino acid residues, lacked sulfur-containing amino acids, and had a low aromatic amino acid content. The protein subunit composition of the vesicles was determined by gel electrophoresis in (i) 0.1% sodium dodecyl sulfate at pH 9.0 and (ii) 5 M urea at pH 2.0. The membrane appeared to consist of one protein subunit of MW 50000 daltons. Charge isomers of this subunit were not detected on urea gels. Antiserum prepared against purified gas vesicles of M. aquaticus S1 crossreacted with the gas vesicles of all other gas vacuolate strains of M. aquaticus, as well as those of Prosthecomicrobium pneumaticum, Nostoc muscorum, and Anabaena flos-aquae, indicating that the gas vesicles of these widely divergent organisms have some antigenic determinants in common.
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PMID:Isolation and characterization of gas vesicles from Microcyclus aquaticus. 40 98

Antibodies to adenosine were elicited in rabbits by immunization with bovine serum albumin-adenosine conjugate. The antibodies were purified and fractionated on two affinity columns (Sepharose-oligo(A) and Sepharose-AMP). Two families of antibodies have been obtained. The antibodies purified on the Sepharose-oligo(A) column react with poly(A) while those purified on the Sepharose-AMP column do not, as shown by gel diffusion. The association constants for the binding of Fab fragments or IgG purified on the Sepharose-oligo(A) column and several haptens were deduced from dialysis equilibrium, fluorescence quenching and displacement of AMP-fluorescein conjugate. The antibodies mainly recognize adenine, and the ribose or the phosphate group of (or AMP derivatives) do not play a critical role in the interaction. Thermodynamic parameters for adenosine-Fab fragments complexes have been determined deltaH degrees = 16 kcal/mole and deltaS degrees = - 15 cal. degree-1 mole-1. Circular dichroism studies indicate that about three nucleotide residues penetrate the binding site of Fab fragments.
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PMID:Purification and specificity of antibodies to adenosine. 40 59

1. Fluxes and distribution of Ca were studied in the perfused rat liver. Kinetic analysis of (45)Ca exchange revealed three compartments with time constants of 4, 14 and 223 min, pool sizes of 250, 385 and 670 mumole.kg(-1) wet wt. respectively, and one non-exchangeable compartment of 400 mumole.kg(-1).2. (45)Ca uptake by in situ mitochondria followed, as a function of cell loading time, a mono-exponential function with a time constant of 16 min. This suggests that the second compartment may be identified as the intracellular pool of Ca. The calculated cell transmembrane flux of Ca was 28 mumole.kg(-1) min(-1) or 0.17 p-mole.cm(-2).sec(-1).3. The maximum (45)Ca uptake by in situ mitochondria was 2.3 n-mole.mg(-1) of protein which represents, on the basis of 50 mg of mitochondrial protein per g of fresh liver, 115 mumole.kg(-1) or 30% of the cytoplasmic pool. A pool of 10.8 n-mole.mg(-1) protein (or 540 mumole.kg(-1)) of non-exchangeable Ca (at steady state) was probably in the form of Ca phosphate precipitated in the mitochondrial matrix.4. Extracellular Ca pools were studied using competitor of Ca binding (La) or Ca chelators (EGTA). La displaced specifically a homogeneous pool of Ca (tau = 5.1 min) which represented a fraction (55 mumole.kg(-1)) of the rapidly exchangeable Ca (first compartment) without perturbing other external pools. On the other hand, EGTA displaced completely that compartment, and about 85% of the Ca of the third compartment. These results suggest that the first and the major fraction of the third compartments are extracellular. They account for 63% of total exchangeable Ca.5. A model of distribution and exchange of Ca in hepatocytes is proposed.
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PMID:Fluxes and distribution of calcium in rat liver cells: kinetic analysis and identification of pools. 41 57

1. The oxygen consumption and the movements of labelled phosphate were measured in garfish olfactory nerve at rest and during activity.2. In solutions with 2.5 mM-K and 0.2 mM-phosphate the resting oxygen consumption was 0.206 m-mole/kg.min; activity at 2 sec(-1) produced an extra oxygen consumption of 2.46 mumole/kg.impulse. The extra oxygen consumption declined exponentially with a time constant of 2.62 min at 22-26 degrees C.3. The phosphate efflux, measured simultaneously, had a resting efflux rate constant of 1.24 x 10(-3) min(-1); activity at 2 sec(-1) produced an extra fractional loss of 9.38 x 10(-6) impulse(-1). The increase in phosphate efflux followed almost the same time course as the increase in oxygen consumption.4. Increasing the frequency of stimulation from 2 sec(-1) to 3 or 5 sec(-1) decreased both the extra oxygen consumption and the extra fractional loss of phosphate. When the frequency was decreased to 0.5 or 1 sec(-1) the extra oxygen consumption per impulse increased, while the extra phosphate liberation was lowered.5. Changing the phosphate concentration did not much affect the extra oxygen consumption; on the other hand, lowering or increasing the phosphate from the standard 0.2 mM decreased both the resting and the stimulated phosphate efflux.6. Lowering the K from the standard 2.5 mM did not affect the extra oxygen consumption, but increased both the resting and the extra loss of phosphate. At higher K concentrations the extra oxygen consumption and the extra fractional loss of phosphate decreased without much change in the resting phosphate efflux.7. Application of 1-20 muM-strophanthidin produced a transient decrease in the resting phosphate efflux without much change in resting oxygen consumption. With 10 or 20 muM-strophanthidin the extra fractional loss of phosphate and the extra oxygen consumption were both lowered in approximately the same proportions.8. The findings are consistent with the hypothesis that the increase in intracellular inorganic phosphate that results from increased break-down of ATP after activity, is the main cause for the increased phosphate efflux. A fraction of the increase in intracellular phosphate only appears to be liberated to the outside, the value of the fraction depending on the resting phosphate efflux before activity.9. The initial increase in intracellular inorganic phosphate after an impulse, estimated from the oxygen consumption or the phosphate fluxes, appears to be about 12-19 mumole/kg nerve, remarkably close to the value known from chemical analysis.
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PMID:Phosphate efflux and oxygen consumption in small non-myelinated nerve fibres at rest and during activity. 43 Apr 13

Female sex and estrogen administration are associated with increased hepatic production of triglyceride-rich lipoproteins; the basis for this has not been fully elucidated. Inasmuch as hepatic lipoprotein production is also influenced by FFA availability and triglyceride biosynthesis, we investigated sex differences in FFA utilization in rat hepatocyte suspensions and in the components of the triglyceride biosynthetic pathway. Isolated adult rat hepatocyte suspensions were incubated with albumin-bound [(14)C]oleate for up to 15 min. At physiological and low oleate concentrations, cells from females incorporated significantly more (14)C into glycerolipids, especially triglycerides, and into oxidation products than did male cells, per milligram cell protein. At 0.44 mM oleate, incorporation into triglycerides in female cells was approximately twice that in male cells. Comparable sex differences were observed in cells from fasted animals and when [(14)C]-glycerol incorporation was measured. At higher oleate concentrations, i.e., fatty acid:albumin mole ratios in excess of 2:1, these sex differences were no longer demonstrable, suggesting that maximal rates of fatty acid esterification and oxidation were similar in female and male cells. In female and male hepatic microsomes, specific activities of long chain acyl coenzyme A synthetase, phosphatidate phosphohydrolase, and diglyceride acyltransferase were similar, but glycerol-3-phosphate acyltransferase activity was slightly greater in females at certain substrate concentrations. Microsomal incorporation of [(14)C]oleate into total glycerolipids was not significantly greater in females. In further contrast to intact cells, microsomal incorporation of [(14)C]oleate into triglycerides, although significantly greater in female microsomes, accounted for only a small fraction of the fatty acid esterified.The binding affinity and stoichiometry of partially purified female hepatic fatty acid binding protein (FABP) were similar to those of male FABP. In contrast, the concentration of FABP, per milligram cytosolic protein, was 44% greater in female liver than in male, as indicated by measurement of [(14)C]oleate binding and of 280 nm OD in the FABP fraction of 105,000 g supernate after gel filtration chromatography. These experiments demonstrate profound sex differences in hepatocyte utilization of long chain fatty acids at concentrations within and below the physiological range, and suggest that these are attributable at least in part to corresponding differences in cytosolic FABP concentration. At higher FFA concentrations, sex differences in hepatocyte FFA utilization are virtually eliminated, suggesting that under these conditions, differences in FABP concentration are not rate determining. Sex differences in hepatic lipoprotein production may largely reflect these important differences in the initial stages of hepatocyte FFA utilization.
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PMID:Sex differences in long chain fatty acid utilization and fatty acid binding protein concentration in rat liver. 44 53


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