Lack of first-pass metabolism of ethanol at blood concentrations in the social drinking range

Previously published data are displayed in a new manner and show that there is complete systemic availability of oral doses of 23-47 g of ethanol (0.35-0.75 g/kg or 30-60 ml of 95% ethanol) in man when administered in the fasting state relative to an intravenous infusion of the same doses administered over a 2-hr period. A previous report by other authors that oral ethanol (0.15 g/kg) in man had a mean systemic availability of only 29% is explained by the fact that the subjects were fed one hour prior to administration of the alcohol and that the intravenous dose was infused over only a 20 minute period.     

Mannitol metabolism in cultured plant cells

Non-structural storage carbohydrates were measured in 9-day-old barley ( Hordeum vulgare L. cv. Brant) primary leaves. Accumulation rates of starch, sucrose and total non-structural carbohydrates (TNC) were approximately linear when measured between 2- and 12-h of light. Progressively higher TNC accumulation rates were observed at higher irradiance levels (i.e., comparing 250, 550 and 1050 ·mol m⁻² s⁻¹). Synthesis of a low-molecular-weight fructan also was enhanced by high irradiances. Low irradiance treatments decreased leaf sucrose levels and there was a corresponding increase in the lag period preceding starch synthesis in the light. Increased starch accumulation rates were usually observed when sucrose concentrations were high. These and other results suggested that cytosolic sucrose concentrations affected starch metabolism in the chloroplast. However, sucrose accumulation rates increased and starch storage decreased when barley seedlings were transferred from 20 to 10°C during the light period. Lowering the night temperature from 20 to 10°C for a single dark period 8-days after planting increased the TNC content of barley primary leaves at the beginning of day nine. In this experiment, TNC accumulation rates of treated and untreated leaves were similar. Changes in the accumulation rate of TNC were usually observed within 2- to 4-h after barley seedlings were exposed to altered environmental conditions. Monitoring rapid changes in leaf carbohydrate levels is a sensitive method for assessing the effects of environmental treatments on photosynthetic metabolism.     

Variation in cadmium accumulation potential and tissue distribution of cadmium in tobacco

Variation in Cd accumulation between Nicotiana species but not varieties has been observed in seedlings grown in solution culture with moderate-to-low levels of Cd. Nicotiana tabacum has been characterized as a leaf and root accumulator while Nicotiana rustica is shown to be primarily a root accumulator, having about half the leaf Cd per gram dry weight of N. tabacum. This phenotype is retained in the mature N. rustica plant. To characterize these two species which differ in their modes of Cd accumulation, tissue Cd distribution, partitioning of metal in soluble and insoluble fractions and the contribution of soluble Cd-binding proteins (peptides) to total plant Cd was assessed using mature solution cultured plants. Metal accumulation was highest in the most mature leaves and in young roots. The preponderance of young roots in N. rustica may, in part, account for low leaf/high root Cd accumulation in this species. While Cd-binding peptides appear to be a principal form of Cd in leaves and roots of seedlings and these also occur in mature leaves, Cd is equally distributed between soluble (about 80% as Cd-binding peptide) and uncharacterized insoluble forms in mature plant roots.     

Primary and secondary chloride transport in Halobacterium halobium.

Chloride uptake in intact cells of Halobacterium halobium was characterized by rates of influx and efflux of 36Cl- under conditions of light, respiration, or both. Halobacterial mutant strains with and without retinal transport proteins allowed study of the effects of halorhodopsin and bacteriorhodopsin under illumination. Two structurally independent chloride transport systems could be distinguished: halorhodopsin, the already known light-driven chloride pump, and a newly described secondary uptake system, which was energized by respiration or by light via bacteriorhodopsin.     

Molecular cloning and characterization of the Endo B cytokeratin expressed in preimplantation mouse embryos

A cDNA clone of a keratin-related, intermediate filament protein, designated Endo B, was constructed from size-fractionated parietal endodermal mRNA and characterized. The 1466-nucleotide cDNA insert contains an open reading frame of 1272 nucleotides that would result in 5' and 3' noncoding sequences of 54 and 60 nucleotides, respectively. The predicted amino acid composition, molecular weight (47,400), and peptide pattern correlate well with data obtained on the isolated protein. The predicted amino acid sequence fits easily into the general domain structure suggested for all intermediate filament proteins with a unique amino-terminal head domain, a large conserved central domain of predominantly alpha-helical structure, and a relatively unique carboxyl-terminal or tail domain. Over the entire molecule, Endo B is 43% identical with human 52-kDa epidermal type I keratin. However, over two of the three regions contained in the central domain that are predicted to form coiled-coil structures, the Endo B is 54-68% identical with other type I keratin sequences. This homology, along with the presence of the completely conserved sequence DNARLAADDFR-KYE, which is found in all type I keratins, permits the unambiguous identification of Endo B as a type I keratin. Comparison of the Endo B sequence to other intermediate filament proteins reveals 22 residues which are identical in all intermediate filament proteins regardless of whether filament formation requires only one type of protein subunit (vimentin, desmin, glial fibrillar acidic protein, or a neurofilament protein) or two dissimilar types (type I and type II keratins). Endo B mRNA was detectable in RNA isolated from F9 cells treated with retinoic acid for 48 h. Approximately three to five genes homologous to Endo B were detected in the mouse genome.     

Linear programming analysis of VA/Q distributions: limits on central moments

Linear programming examines the boundaries of infinite sets. We used this method with the multiple-inert gas-elimination technique to examine the central moments and arterial blood gases of the infinite family of ventilation perfusion (VA/Q) distributions that are compatible with a measured inert gas-retention set. A linear program was applied with Monte-Carlo error simulation to theoretical retention data, and 95% confidence intervals were constructed for the first three moments (mean, dispersion, and skew) and the arterial PO2 and PCO2 of all compatible blood flow distributions. Six typical cases were studied. Results demonstrate narrow confidence intervals for both the lower moments and predicted arterial blood gases of all test cases, which widen as moment number or error increase. We conclude that the blood gas composition and basic structure of all compatible VA/Q distributions are tightly constrained and that even subtle changes in this structure, as may occur experimentally, can be identified.     

A coordinate relationship between theGALK and theTK1 genes of the Chinese hamster

Chinese hamster cells in culture were treated with various concentrations of thymidine, 5-bromodeoxyuridine, trifluorothymidine, and 2-deoxy-D-galactose. Selection was made for deficiencies in the activities of galactokinase and thymidine kinase. Selection in the presence of thymidine, 5-bromodeoxyuridine, and trifluorothymidine was expected to produce clones deficient in thymidine kinase only, whereas those deficient in galactokinase were expected to be selected in the presence of 2-deoxy-D-galactose. However, it was found that clones growing in the presence of these inhibitors were frequently deficient in both enzymes. Or if a clone was deficient in only one, the deficiency frequently was not expected according to the selection procedure. This indicates some sort of coordinate relationship between the two gene loci, GALK and TK1, which specify galactokinase and thymidine kinase, respectively. GALK and TK1 are linked in all primates and rodents in which linkage determinations have been made. It is therefore probable that this linkage has been conserved for a long period of time. It is suggested that the apparent relationship between the two genes shown by the data presented here, as well as by others, supports the conclusion that linkage has been conserved by natural selection and is therefore not fortuitous.     

2'-Nor-cGMP: a seco-cyclic nucleotide with powerful anti-DNA-viral activity

As part of our study of antiherpetic acyclonucleosides, we synthesized a cyclic GMP analog, 9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]guanine P-oxide, sodium salt (2'-nor-cGMP), and discovered its potent and broad spectrum anti-DNA-viral activities. 2'-Nor-cGMP inhibits the replication of many DNA viruses, including herpes simplex virus, human cytomegalovirus, vaccinia, SV40, and adenovirus, but does not inhibit RNA viruses. In plaque reduction studies this potent antiviral agent is also approximately 10-fold more potent than 9-(1,3-dihydroxy-2-propoxymethyl)guanine (2'NDG) against varicella-zoster virus and inhibits cell transformation by bovine papilloma virus. Unlike 2'NDG, the potent activity of 2'-nor-cGMP against herpes virus is not dependent upon the action of virus-specified thymidine kinase. Intercellular metabolism of 2'-nor-cGMP produced small amounts of 2'NDG triphosphate which were insufficient to account for the antiviral activity observed, implying that this potent anti-DNA-viral agent operates by a mechanism different from that of known acyclonucleosides.     

Inhibition of glycine N-methyltransferase activity by folate derivatives: implications for regulation of methyl group metabolism

Glycine N-methyltransferase, an enzyme that uses S-adenosylmethionine to methylate glycine with the production of sarcosine, was recently shown to be identical with a major folate binding protein of rat liver (Cook, R.J. and Wagner, C. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 3631-3634). We now present evidence that 5-methyltetrahydropteroylpentaglutamate (5-CH3-H4PteGlu5) is bound with high specificity, and is a powerful inhibitor of the enzyme. It is proposed that this information may be used to modify the "methyl trap" hypothesis which describes how the availability of one-carbon units is regulated by folate, vitamin B12 and methionine.     

Characterization of the fluorophore 4-heptadecyl-7-hydroxycoumarin: a probe for the head-group region of lipid bilayers and biological membranes

The fluorophore 4-heptadecyl-7-hydroxycoumarin was used as a probe to study the properties of phospholipid bilayers at the lipid-water interface. To this end, the steady-state fluorescence anisotropy, the differential polarized phase fluorometry, and the emission lifetime of the fluorophore were measured in isotropic viscous medium, in lipid vesicles, and in the membrane of vesicular stomatitis virus. In the isotropic medium (glycerol), the probe showed an increase in the steady-state fluorescence anisotropy with a decrease in temperature, but the emission lifetime was unaffected by the change in temperature. In glycerol, the observed and predicted values for maximum differential tangents of the probe were identical, indicating that in isotropic medium 4-heptadecyl-7-hydroxycoumarin is a free rotator. Nuclear magnetic resonance and differential scanning calorimetric studies with lipid vesicles containing 1-2 mol % of the fluorophore indicated that the packaging density of the choline head groups was affected in the presence of the probe with almost no effect on the fatty acyl chains. The fluorophore partitioned equally well in the gel and liquid-crystalline phase of the lipids in the membrane, and the phase transition of the bilayer lipids was reflected in the steady-state fluorescence anisotropy of the probe. The presence of cholesterol in the lipid vesicles had a relatively small effect on the dynamics of lipids in the liquid-crystalline state, but a significant disordering effect was noted in the gel state. One of the most favorable properties of the probe is that its emission lifetime was unaffected by the physical state of the lipids or by the temperature.(ABSTRACT TRUNCATED AT 250 WORDS)